DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

1

Draft Guideline for the Prevention of 

Surgical Site Infection

Sandra I. Berríos-Torres, MD1, Craig A. Umscheid, MD, MSCE2, Dale W. Bratzler, DO, MPH3, 

Brian Leas, MA, MS2, Erin C. Stone, MS1, Rachel R. Kelz, MD, MSCE, FACS2, Caroline Reinke, MD, 

MPH2, Sherry Morgan, RN, MLS, PhD2, Joseph S. Solomkin, MD4, John E. Mazuski, MD, PhD5, E. 

Patchen Dellinger, MD6

, Kamal Itani, MD7

, Elie F. Berbari, MD8, John Segreti, MD9, Javad Parvizi, 

MD10, Joan Blanchard, MSS,BSN,RN,CNOR,CIC11, George Allen, PhD, CIC, CNOR12, J. A. J. W. 

Kluytmans, MD13, Rodney Donlan, PhD1, William P. Schecter, MD4and the Healthcare Infection 

Control Practices Advisory Committee15

1

Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA; 

2 Center for 

Evidence-based Practice, University of Pennsylvania Health System, Philadelphia, PA; 

3

University of Oklahoma 

Health Sciences Center, College of Public Health, Oklahoma City, OK;

4

University of Cincinnati, University of 

Cincinnati College of Medicine, Cincinnati, OH; 

5Washington University, Washington University School of Medicine, 

Saint Louis, MO; 

6

University of Washington Medical Center, Seattle, WA; 

7

Veterans Affairs Boston Healthcare 

System, Boston, MA; 

8 Mayo Clinic College of Medicine, Rochester, MN; 9

Rush University Medical Center, Chicago, 

IL; 

10

, Rothman Institute, Philadelphia, PA; 

11

Littleton Adventist Hospital, Quality Department, Denver, CO; 

12

Downstate Medical Center, Brooklyn, NY; 

13

Laboratory for Microbiology and Infection Control

Amphia Hospital, Breda, the Netherlands; 

14University of California, San Francisco, San Francisco General Hospital

San Francisco, CA
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

2

15Healthcare Infection Control Practices Advisory Committee (HICPAC)

Membership List, as of November 2013

Chair: Neil O. Fishman, MD, University of Pennsylvania Health System, Philadelphia, PA 

Designated Federal Officer: Jeffrey C. Hageman, MHS, Division of Healthcare Quality, Promotion, 

National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta, GA

Members: Dale W. Bratzler, DO, MPH, University of Oklahoma Health Sciences Center, Oklahoma City, 

OK; Ruth M. Carrico, PhD, RN, CIC, University of Louisville School of Medicine, Louisville, KY; Daniel J.

Diekema, MD, University of Iowa Carver College of Medicine, Iowa City, IA; Alexis Elward, MD, 

Washington University School of Medicine, St. Louis, MO; Mary K. Hayden, MD, Rush University Medical 

Center and Rush Medical College, Chicago, IL; Susan Huang, MD, MPH,University of California Irvine 

School of Medicine, Orange, CA; Gina Pugliese, RN, MS, Premier Healthcare Alliance, St. Joseph, 

Michigan; Selwyn O. Rogers Jr., MD, MPH, FACS, Temple University School of Medicine, Philadelphia, 

PA; Tom Talbot, MD MPH, Vanderbilt University School of Medicine and Medical Center, Nashville, TN; 

Michael L. Tapper, MD, Lenox Hill Hospital, New York City, NY; Deborah S. Yokoe, MD, MPH, Brigham & 

Women's Hospital and Harvard Medical School, Boston, MA.

Ex-Officio Members: Agency for Healthcare Research and Quality, William B. Baine, MD, Rockville, MD; 

Center for Medicare & Medicaid Services, Daniel Schwartz, MD, MBA, Baltimore, MD; Food and Drug 

Administration, vacant, Rockville, MD; Health Resources and Services Administration, Paul D. Moore, 

PhD, Rockville, MD; National Institutes of Health, David Henderson, MD, Bethesda, MD; Department of 

Veterans Affairs, Gary A. Roselle, MD, Cincinnati, OH.

Liaison Representatives: America’s Essential Hospitals, Silvia Munoz-Price, MD, Miami, FL; American 

College of Occupational and Environmental Medicine, Mark Russi, MD, MPH, New Haven, CT; American 

Health Care Association, Sandra L. Fitzler, RN, Washington, DC; American Hospital Association,

Nancy Foster, Washington, DC; Association of periOperative Registered Nurse, Amber Wood, MSN, RN, 

CNOR, CIC, CPN; Denver, CO; Association of Professionals of Infection 

Control and Epidemiology, Inc., Michael Anne Preas, RN, CIC, Baltimore MD; Association of State and 

Territorial Health Officials, Emily Lutterloh, MD, MPH, Albany, NY; Council of State and Territorial 

Epidemiologists, Marion Kainer MD, MPH, Nashville, TN; Consumers Union, 

Lisa McGiffert, Yonkers, NY; DNV Healthcare, Inc., Janet Franck, RN, MBA, CIC, Chicago, IL; Healthcare 

Facilities Accreditation Program, Donna Tiberi, RN, MHA, Chicago, IL; Infectious Disease Society of 

America, W. Charles Huskins, MD, MSc, Rochester, MN; National Association of County and City Health 

Officials, Diana Gaviria MD, MPH, Martinsburg, WV; Public Health Agency of Canada, Kathleen Dunn, 

BScN, MN, RN, Ottawa, Ontario, Canada; Society for Healthcare Epidemiology of America, Mark E. Rupp, 

MD, Omaha, NE; Society of Critical Care Medicine, Michael D. Howell, MD MPH, Chicago, IL; Society of 

Hospital Medicine, Sanjay Saint, MD, MPH, Ann Arbor, MI; Surgical Infection Society (SIS), Robert, G.

Sawyer, MD, FACS, FIDSA, FCCM, Charlottesville, VA; The Joint Commission, Margaret Vanamringe, MHS, 

Washington, DC.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

3

Acknowledgement

We would like to thank the many individuals and organizations who provided valuable feedback 

on the guideline during the development process. We would especially like to recognize and 

thank the HICPAC liaison organizations as well as those surgical societies (i.e., American College 

of Surgeons, Musculoskeletal Infection Society, and American Academy of Orthopaedic 

Surgeons) who provided input throughout the development process.

We would like to especially thank the following experts for their input throughout the process: 

Rajender Agarwal MD, MHP, J. William Costerton, PhD, Thomas Hunt MD, Bernard Morrey MD, 

Lena M. Napolitano MD, FACS, FCCP, FCCM, Douglas Osmon MD, Robin Patel, MD (CM), 

FRCP(C), D(ABMM), FIDSA, FACP, and Mark Shirtliff, PhD. The opinions of the reviewers might 

not be reflected in all of the recommendations contained in this document.

Disclosures of Competing Interests

The authors S.I.B.T., E.F.B., J.B., R.D. E.S., J.S.S., and W.P.S. report no actual or potential conflicts 

of interest. G.A. reports lecturer fees for Ethicon and royalties from Wolters Kluwer Publishers 

as an author for Infection control for healthcare facilities. D.B. is a consultant for both the 

Oklahoma Foundation for Medical Quality, Telligen (a non-profit Medicaid External Quality 

Review Organization); his institution received payment for his lectures including service on 

speakers’ bureaus from both Premier and Janssen pharmaceuticals. E.P.D. reports received 

grants for clinical research from, served on an advisory board for, and/or lectured for honoraria 

from, Merck, Baxter, Ortho-McNeil, Targanta, Schering-Plough, WebEx, Astellas, Care Fusion, 

Durata, Pfizer, Applied Medical, Rib-X, Affinium, and 3M. K.I. reports his institution receiving 

grants from Merck, Cubist and Trius for research trials; clinical advisory board membership at 

Forrest Pharmaceuticals; payment for development of educational presentations for Med 

Direct and Avid Education; J.E.M. is a paid consultant for Forest Laboratories, MedImmune and 

Pfizer, and lecturer fees from Forest Laboratories, Merck/Merck Sharp and Dohme, and Pfizer; 

while his institution receives funding for his consultancy to Astra-Zenca and grants from AstraZeneca, Merck/MSD and Tetraphase. J.P. reports his Institution receiving monies for his board 

membership of Journal of Arthroplasty, the Philadelphia Orthopedic Society, EOA, United 

Healthcare, Magnifi Group, 3M, and the Journal of Bone and Joint Surgery – America; 

consulting for Zimmer, Smith and Nephew, Convatech, TissueGene, Ceramtech, OsteoMEM, 3M 

and Cadence with money paid to his institution; grants to his institution from Orthopaedic 

Research and Education Foundation, Stryker, Depuy, Zimmer, Baxter, 3M, Biomemetics, 

Ceramtec, and Smith and Nephew; royalties paid to his institution from SmarTech, Elsevier, 

Wolters Kluwer, Slack, Hip Innovations Technology, CD Diagnostics, Jaypee Publishers and 

Datatrace. J.S. reports lecture fees from Pfizer, Merck, and Forest; and stocks and/or stock 

options from Pfizer. 

R.K., B.L., S.M., C.R., and C.A.U. all received funding from CDC to support the guideline 

development process. They report no other conflict of interest.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

4

Table of Contents

Abbreviations................................................................................................................................................5

I. Executive Summary....................................................................................................................................6

II. Summary of Recommendations..............................................................................................................11

CORE SECTION.........................................................................................................................................11

PROSTHETIC JOINT ARTHROPLASTY SECTION.........................................................................................14

III. Background ............................................................................................................................................17

IV. Scope and Purpose ................................................................................................................................20

V. Methods..................................................................................................................................................23

VI. Evidence Review: Core section..............................................................................................................28

PARENTERAL ANTIMICROBIAL PROPHYLAXIS (AMP)..............................................................................28

NON-PARENTERAL ANTIMICROBIALPROPHYLAXIS.................................................................................32

GLYCEMIC CONTROL ...............................................................................................................................36

NORMOTHERMIA....................................................................................................................................38

OXYGENATION ........................................................................................................................................39

ANTISEPTIC PROPHYLAXIS.......................................................................................................................43

VII. Evidence Review- Prosthetic Joint Arthroplasty section ......................................................................53

BLOOD TRANSFUSION.............................................................................................................................53

SYSTEMIC IMMUNOSUPPRESSIVE THERAPY...........................................................................................56

INTRA-ARTICULAR CORTICOSTEROID INJECTIONS..................................................................................61

ANTICOAGULATION ................................................................................................................................63

ORTHOPAEDIC SPACE SUIT .....................................................................................................................68

POSTOPERATIVE AMP DURATION IN PROSTHETIC JOINT ARTHROPLASTY WITH THE USE OF A DRAIN 69

BIOFILM...................................................................................................................................................70

REFERENCES................................................................................................................................................73
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

5

Abbreviations

AMP Antimicrobial prophylaxis

APRP Autologous platelet rich plasma

ASA Acetylsalicylic acid (aspirin)

ASEPSIS Additional treatment, the presence of Serous discharge, Erythema, Purulent 

exudate, and Separation of the deep tissues, the Isolation of bacteria, and the 

duration of inpatient Stay 

BMI Body mass index

°C Celsius

CABG Coronary artery bypass graft 

CDC Centers for Disease Control and Prevention

CHG Chlorhexidine gluconate

CMA Centers for Medicare & Medicaid Services

DHQP Division of Healthcare Quality Promotion

DMARD Disease Modifying Antirheumatic Drug

FDA Food and Drug Administration

FiO2 Fraction of inspired oxygen

GRADE Grading of Recommendations Assessment, Development, and Evaluation

HICPAC Healthcare Infection Control Practices Advisory Committee

ICD9-CM International Classification of Diseases, 9th Revision, Clinical Modification

INR International Normalized Ratio

LMWH Low molecular weight heparin

MRSA Methicillin-resistant Staphylococcus aureus

NICU Neonatal Intensive Care Unit

NHSN National Healthcare Safety Network

OBS Observational study

OR Odds ratio

P P value

PJI Periprosthetic joint infection

RA Rheumatoid arthritis

RCT Randomized control trial

RR Relative risk

SICU Surgical intensive care unit

SD Standard deviation

SR Systematic review

SSI Surgical site infection

THA Total hip arthroplasty

TKA Total knee arthroplasty

TNF Tumor Necrosis Factor

VTE Venous thromboembolism

WBC White blood cell
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

6

I. Executive Summary

Surgical site infections (SSI) are infections of the incision or organ/space occurring after surgery. 

1,2

Prevention of SSI is increasingly important as the number of surgical procedures performed 

continues to increase.

3,4

Surgical patients presenting with more complex comorbidities5 and 

the emergence of antimicrobial resistant pathogens increase the cost and challenge of treating 

SSIs.

6-8

Public reporting of process, outcome, and other quality improvement measures is now 

required,

9,10

 and reimbursements11 for treating SSIs are being reduced or denied.

The Draft Guideline for Prevention of Surgical Site Infection addresses new and updated 

strategies for the prevention of SSI in healthcare settings.

12 This guideline does not provide 

comprehensive infection control recommendations for prevention of SSIs. The select areas of 

focus were informed by feedback received from clinical experts and input from the Healthcare 

Infection Control Practices Advisory Committee (HICPAC), a federal advisory committee to the 

Centers for Disease Control and Prevention (CDC). The Core section includes recommendations 

intended to be generalizable across surgical procedures. The Prosthetic Joint Arthroplasty 

section focuses on this frequently performed procedure with a high human and economic 

burden. This guideline does not specifically address SSI prevention issues unique to: burns, 

trauma, surgical incisions allowed to heal by secondary intention, transplant procedures, 

transmission of blood borne pathogens from healthcare personnel to the patient, pediatric 

surgical practice, minimally invasive procedures, procedures performed outside the operating 

room (e.g., endoscopic procedures), non-surgical invasive procedures (e.g., cardiac 

catheterization, interventional radiology), and other procedures or conditions not specifically 

mentioned. In general, SSI prevention measures deemed effective in adults are also indicated 

in the pediatric population, and those effective in the operating room can be adapted or 

modified for other settings. In addition, this update does not address SSI surveillance or public 

reporting. 

1,2

Recommendations on infection control in healthcare personnel,

13 environmental 

infection control,

14 and disinfection and sterilization of medical devices15 in health care settings 

all of which may have an impact on the incidence of SSI, are topics addressed by other 

guidelines. 

This document is intended for use by surgeons, physician assistants, perioperative nurses and 

other allied perioperative assistive personnel, anesthesia providers, postoperative inpatient and 

clinic nurses, infection prevention staff, healthcare epidemiologists, healthcare administrators, 

other healthcare providers, and persons responsible for developing, implementing, delivering, 

and evaluating infection prevention and control programs for surgical procedures performed in 

an operating room (inpatient or ambulatory setting). The guideline can also be used as a 

resource for professional societies or organizations that wish to develop more detailed 

implementation guidance or to identify future research priorities where there are evidence 

gaps for the prevention of SSI.

Our goal was to develop a guideline based on a targeted systematic review of the best available 

evidence, with explicit links between the evidence and recommendations. To accomplish this 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

7

we used an adapted Grading of Recommendations, Assessment, Development, and Evaluation 

(GRADE) system for evaluating quality of evidence and determining strength of 

recommendations.

16-19 The methodology, structure, and components of this guideline were 

adopted by the Centers for Disease Control and Prevention (CDC) and Healthcare Infection 

Control Practices Advisory Committee (HICPAC) in 2009.

20,21 A more detailed description of our 

approach is found in the Methods section. Evidence-based recommendations were crosschecked with those from other guidelines identified in an initial systematic search. 

The Key Questions, Evidence Review, and Summary of Recommendations, are each organized 

as follows: 

CORE section

To evaluate the evidence on SSI prevention across multiple surgical specialties and procedures, 

published material addressing ten key questions and related subquestions were examined:

Parenteral antimicrobial prophylaxis (AMP)

Q1. What are the most effective strategies for administering parenteral AMP to reduce the risk 

of SSI? 

A. What is the optimal timing of preoperative AMP?

B. What is the optimal timing of AMP in cesarean section: prior to skin incision or at cord 

clamping?

C. How safe and effective is weight-adjusted AMP dosing?

D. How safe and effective is intraoperative redosing of AMP?

E. How safe and effective is postoperative AMP and what is the optimal duration?

Non-parenteral antimicrobial prophylaxis

Q2. What are the most effective strategies for administering non-parenteral antimicrobial 

prophylaxis at the surgical incision to reduce the risk of SSI?

A. How safe and effective is antimicrobial irrigation?

B. How safe and effective are antimicrobial agents applied to the surgical incision?

C. How safe and effective are antimicrobial-coated sutures; when and how should they 

be used?

D. How safe and effective are antimicrobial dressings applied to surgical incisions

following primary closure in the operating room?

Glycemic control

Q3. How do perioperative blood glucose and hemoglobin A1C levels impact the risk of SSI, and 

what are their optimal perioperative target levels in diabetic and non-diabetic patients?

Normothermia

Q4. How safe and effective is the maintenance of perioperative normothermia in reducing the 

risk of SSI? 

Q5. What are the most effective strategies for achieving and maintaining perioperative 

normothermia? 

Oxygenation

Q6. In patients with normal pulmonary function, how safe and effective is the perioperative use 

of increased fraction of inspired oxygen (FiO2) in reducing the risk of SSI?
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

8

Q7. What is the optimal target FiO2 to reduce the risk of SSI; how and when should it be 

administered?

Antiseptic Prophylaxis

Q8. What are the most effective strategies for preparing the patient’s skin prior to surgery to 

reduce the risk of SSI?

A. How safe and effective is preoperative antiseptic bathing or showering? 

B. How safe and effective are antiseptic skin preparation agents individually and in 

combination?

C. How safe and effective is the application of an antimicrobial sealant immediately 

following skin preparation?

D. How safe and effective are plastic adhesive drapes? 

Q9. How safe and effective is antiseptic irrigation prior to closing the surgical incision?

Q10. How safe and effective is repeat application of an antiseptic skin preparation agent to the 

surgical site immediately prior to closing the surgical incision?

PROSTHETIC JOINT ARTHROPLASTY Section

To evaluate the evidence on SSI prevention in prosthetic joint arthroplasty procedures, 

published material addressing 10 key questions and related subquestions were examined:

Blood transfusion

Q11. How do perioperative blood transfusions impact the risk of SSI in prosthetic joint 

arthroplasty patients? 

A. Are specific blood products associated with a risk of SSI? 

B. If the risk of SSI is increased, can this effect be isolated from the risk associated with 

more complex cases?

C. How does the volume of transfused blood product impact the risk of SSI?

D. How safe and effective is withholding blood transfusion to reduce the risk of SSI?

Systemic immunosuppressive therapy

Q12. How does systemic corticosteroid or other immunosuppressive therapy impact the risk of 

SSI in prosthetic joint arthroplasty patients? 

A. Does the type of agent impact the risk of SSI? 

B. Does the preoperative duration of the therapy impact the risk of SSI?

C. Does the agent dose impact the risk of SSI?

Q13. What are the most effective strategies in managing systemic corticosteroid or other 

immunosuppressive therapy perioperatively to reduce the risk of SSI in prosthetic joint 

arthroplasty patients?

A. How safe and effective is the discontinuation of these agents preoperatively, and 

when should they be resumed?

B. Should the agent dose be adjusted, and if so, for how long?

Q14. What is the optimal duration of postoperative AMP to reduce the risk of SSI in prosthetic 

joint arthroplasty patients who are on systemic corticosteroid or other immunosuppressive 

therapy?

Intra-articular corticosteroid injections
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

9

Q15. How do preoperative intra-articular corticosteroid injections impact the risk of SSI in 

prosthetic joint arthroplasty patients?

Q16. What are the most effective strategies for managing the preoperative use of intraarticular corticosteroid injections to reduce the risk of SSI in prosthetic joint arthroplasty 

patients?

A. Does the length of time between intra-articular corticosteroid injection and 

prosthetic joint arthroplasty impact the risk of SSI?

B. Does the corticosteroid injection dose impact the risk of SSI? 

Anticoagulation

Q17. What are the most effective strategies for managing perioperative venous 

thromboembolism (VTE) prophylaxis to reduce the risk of SSI?

A. Does the risk of SSI differ by individual VTE prophylaxis agent? 

B. What is the optimal timing and duration of perioperative VTE prophylaxis that also 

reduces the risk of SSI?

C. How safe and effective is modifying the dose of the perioperative VTE prophylaxis

agent to reduce the risk of SSI?

Orthopaedic space suit

Q18. How safe and effective are orthopaedic space suits in reducing the risk of SSI in prosthetic 

joint arthroplasty patients, and which healthcare personnel should wear them?

Antimicrobial prophylaxis duration with drain use

Q19. What is the optimal duration of postoperative AMP to reduce the risk of SSI in prosthetic 

joint arthroplasty in the presence of a drain?

Biofilm

Q20. What are the most effective strategies to reduce the risk of biofilm formation and SSI in 

prosthetic joint arthroplasty patients?

A. How effective are cement modifications (i.e., antimicrobial and nanoparticle loading)?

B. How effective are prosthesis surface modifications (i.e., antimicrobial coating, 

galvanic couples, “printing” technologies, and nanotechnology)?

C. How effective are vaccines?

D. How effective are other biofilm control agents (e.g., biofilm dispersants, quorumsensing inhibitors, novel antimicrobial agents)?

Evidence addressing the key questions was used to formulate recommendations and explicit 

links between the evidence and recommendations are available in the Evidence Review in the 

body of the guideline and Evidence Tables and GRADE Tables in the Appendices. Category I 

recommendations are ALL considered strong and should be equally implemented; only the 

quality of the evidence underlying the recommendation that distinguishes between levels A 

and B. Category IC recommendations are required by state or federal regulation and without 

regard to level of supporting evidence. Category II recommendations are considered weak 

recommendations, discretionary for the individual institution, and not intended to be enforced. 

The categorization scheme used in this guideline is presented in Table 1: Summary of 

Recommendations and described further in the Methods section. 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

10

Readers who wish to examine the evidence underlying the recommendations are referred to 

the Evidence Review in the body of the guideline, and the Evidence Tables and GRADE Tables in 

the Appendices. The Evidence Review includes narrative summaries of the data presented in 

the Evidence Tables and GRADE Tables. The Evidence Tables include all study-level data used in 

the guideline, and the GRADE Tables assess the overall quality of the evidence for each 

question and outcome examined. The Appendices also contain a clearly delineated search 

strategy that can be used for periodic updates to ensure that the guideline remains a timely 

resource as new information becomes available.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

11

II. Summary of Recommendations

Table 1. CDC and HICPAC Categorization Scheme for Recommendations*

20,21

Category IA A strong recommendation supported by high to moderate quality*20,21

evidence suggesting net clinical benefits or harms.

Category IB A strong recommendation supported by low-quality evidence 

suggesting net clinical benefits or harms, or an accepted practice (e.g., 

aseptic technique) supported by low to very low-quality evidence.

Category IC A strong recommendation required by state or federal regulation.

Category II A weak recommendation supported by any quality evidence 

suggesting a tradeoff between clinical benefits and harms.

No recommendation/ 

unresolved issue

An unresolved issue for which there is either low to very low-quality 

evidence with uncertain tradeoffs between benefits and harms or no 

published evidence on outcomes deemed critical to weighing the risks 

and benefits of a given intervention.

* Please refer to Methods section and Umscheid et al., “Updating the Guideline Methodology 

of the Healthcare Infection Control Practices Advisory Committee” (HICPAC; 

http://www.cdc.gov/hicpac/pdf/guidelines/2009-10-29HICPAC_GuidelineMethodsFINAL.pdf), 

for the process used to grade quality of evidence and formulate recommendations. 

CORE SECTION

I. PARENTERAL ANTIMICROBIAL PROPHYLAXIS

1A. Administer preoperative antimicrobial agent only when indicated, based on published 

clinical practice guidelines and timed such that a bactericidal concentration of the agent is 

established in the serum and tissues when the incision is made (Category IB) 12 (Key Question 

1A)

 No further refinement of timing can be made for preoperative antimicrobial agent 

based on clinical outcomes. (No recommendation/unresolved issue) (Key Question 1A)

1B. Administer the appropriate parenteral prophylactic antimicrobial agent prior to skin incision 

in all cesarean sections. (Category IA) 22-25 (Key Question 1B)

1C. No recommendation can be made regarding the safety and effectiveness of weight-adjusted

dosing of parenteral prophylactic antimicrobial agents for the prevention of surgical site 

infection. (No recommendation/unresolved issue) (Key Question 1C)

1D. No recommendation can be made regarding the safety and effectiveness of intraoperative 

redosing of parenteral prophylactic antimicrobial agents for the prevention of surgical site 

infection. (No recommendation/unresolved issue) 26 (Key Question 1D)
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

12

1E. In clean and clean-contaminated procedures, do not administer additional prophylactic 

antimicrobial agent doses after the surgical incision is closed in the operating room, even in the 

presence of a drain. (Category IA) 27-65 (Key Question 1E)

II. NON-PARENTERAL ANTIMICROBIAL PROPHYLAXIS

2A.1. No recommendation can be made regarding the safety and effectiveness of 

intraoperative antimicrobial irrigation (e.g., intra-abdominal, deep or subcutaneous tissues) for 

the prevention of surgical site infection. (No recommendation/unresolved issue) (Key Question 

2A)

2A.2. No recommendation can be made regarding the safety and effectiveness of soaking 

prosthetic devices in antimicrobial solutions prior to implantation for the prevention of surgical 

site infection. (No recommendation/ unresolved issue) (Key question 2A)

2B.1. Do not apply antimicrobial agents (i.e., ointments, solutions, powders) to the surgical 

incision for the prevention of surgical site infection (Category IB)

66-72 (Key Question 2B)

2B.2. Application of autologous platelet rich plasma is not necessary for the prevention of 

surgical site infection. (Category II)

73-75 (Key Question 2B)

2C. Use of antimicrobial coated sutures is not necessary for the prevention of surgical site 

infection. (Category II)

76-79 (Key Question 2C)

2D. No recommendation can be made regarding the safety and effectiveness of antimicrobial 

dressings applied to surgical incisions following primary closure in the operating room for the 

prevention of surgical site infection. (No recommendation/ unresolved issue) (Key Question 

2D)

III. GLYCEMIC CONTROL

3A.1. Implement perioperative glycemic control and use blood glucose target levels <200mg/dL 

in diabetic and non-diabetic patients. (Category IA) 80,81 (Key Question 3)

3A.2. No recommendation can be made regarding the safety and effectiveness of lower 

(<200mg/dL) or narrower blood glucose target levels, nor the optimal timing, duration, or 

delivery method of perioperative glycemic control for the prevention of surgical site infection. 

(No recommendation/unresolved issue) (Key Question 3)

3B. No recommendation can be made regarding optimal hemoglobin A1C target levels for the 

prevention of surgical site infection in diabetic and non-diabetic patients. (No 

recommendation/unresolved issue) (Key Question 3)
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

13

IV. NORMOTHERMIA

4. Maintain perioperative normothermia (Category IA) 82-84 (Key Question 4)

5. No recommendation can be made regarding the safety and effectiveness of strategies to 

achieve and maintain normothermia, the lower limit of normothermia, or the optimal timing 

and duration of normothermia for the prevention of surgical site infection. (No 

recommendation/unresolved issue) (Key Question 5)

V. OXYGENATION

6A. For patients with normal pulmonary function undergoing general anesthesia with 

endotracheal intubation, administer increased fraction of inspired oxygen (FiO2) both 

intraoperatively and post-extubation in the immediate postoperative period. To optimize 

tissue oxygen delivery, maintain perioperative normothermia and adequate volume 

replacement. (Category IA) 85-90 (Key Question 6)

6B. No recommendation can be made regarding the safety and effectiveness of administering 

perioperative increased fraction of inspired oxygen (FiO2) for the prevention of surgical site 

infection in patients with normal pulmonary function undergoing either general anesthesia 

without endotracheal intubation or neuraxial anesthesia (i.e., spinal, epidural, or local nerve 

blocks). (No recommendation/unresolved issue) 91 (Key Question 6)

6C. No recommendation can be made regarding the safety and effectiveness of administering 

increased fraction of inspired oxygen (FiO2) via facemask or nasal cannula only during the 

postoperative period for the prevention of surgical site infection in patients with normal 

pulmonary function. (No recommendation/unresolved issue)92,93 (Key Question 6)

7. No recommendation can be made regarding the optimal target level, duration, and delivery 

method of the fraction of inspired oxygen (FiO2) for the prevention of surgical site infection. 

(No recommendation/ unresolved issue) (Key Question 7)

VI. ANTISEPTIC PROPHYLAXIS

8A. Advise patients to shower or bathe (full body) with either soap (antimicrobial or nonantimicrobial) or an antiseptic agent on at least the night before the operative day (Category 

IB) 94-102 (Key Question 8A)

8A.1. No recommendation can be made regarding the optimal timing of the preoperative 

shower or bath, the total number of soap or antiseptic agent applications, or the use of 

chlorhexidine gluconate washcloths for the prevention of surgical site infection. (No 

recommendation/ unresolved issue) (Key Question 8A)
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

14

8B. Perform intraoperative skin preparation with an alcohol-based antiseptic agent, unless

contraindicated. (Category IA) 103-116 (Key Question 8B)

8C. Application of an antimicrobial sealant immediately following intraoperative skin 

preparation is not necessary for the prevention of surgical site infection. (Category II)

117-119

(Key Question 8C)

8D. Use of plastic adhesive drapes with or without antimicrobial properties, is not necessary for 

the prevention of surgical site infection. (Category II) 104,120-124 (Key Question 8D)

9A. Consider intraoperative irrigation of deep or subcutaneous tissues with aqueous iodophor 

solution for the prevention of surgical site infection. Intra-peritoneal lavage with aqueous 

iodophor solution in contaminated or dirty abdominal procedures is not necessary. (Category 

II) 125-131 (Key Question 9)

9B. No recommendation can be made regarding the safety and effectiveness of soaking 

prosthetic devices in antiseptic solutions prior to implantation for the prevention of surgical site 

infection. (No recommendation/unresolved issue) (Key Question 9)

10. No recommendation can be made regarding the safety and effectiveness of repeat 

application of antiseptic agents to the patient’s skin immediately prior to closing the surgical 

incision for the prevention of surgical site infection. (No recommendation/unresolved issue)

132

(Key Question 10)

PROSTHETIC JOINT ARTHROPLASTY SECTION

I. BLOOD TRANSFUSION

11A. No recommendation can be made regarding the perioperative management of blood 

transfusions for the prevention of surgical site infection in prosthetic joint arthroplasty. (No 

recommendation/unresolved issue)133-141 (Key Question 11A-C)

11B. Do not withhold transfusion of necessary blood products from surgical patients as a means 

to prevent surgical site infection (Category IB)12 (Key Question 11D)

II. SYSTEMIC IMMUNOSUPPRESSIVE THERAPY

12 and 13. No recommendation can be made regarding the perioperative management of 

systemic corticosteroid or other immunosuppressive therapy for the prevention of surgical site 

infection in prosthetic joint arthroplasty. (No recommendation/ unresolved issue) 142-148 (Key 

Questions 12 and 13)

14. For prosthetic joint arthroplasty patients on systemic corticosteroid or other 

immunosuppressive therapy, Recommendation 1E applies: In clean and clean-contaminated 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

15

procedures, do not administer additional prophylactic antimicrobial agent doses after the 

surgical incision is closed in the operating room, even in the presence of a drain. (Category 

IA)27-65 (Key Question 14)

III. INTRA-ARTICULAR CORTICOSTEROID INJECTION

15 and 16. No recommendation can be made regarding the management of preoperative intraarticular corticosteroid injection for the prevention of surgical site infection in prosthetic joint 

arthroplasty. (No recommendation/ unresolved issue) 149-153 (Key Questions 15 and 16)

IV. ANTICOAGULATION

17. No recommendation can be made regarding the perioperative management of venous 

thromboembolism prophylaxis for the prevention of surgical site infection in prosthetic joint 

arthroplasty. (No recommendation/unresolved issue)154-167 (Key Question 17)

V. ORTHOPAEDIC SPACE SUIT

18. No recommendation can be made regarding the safety and effectiveness of orthopaedic 

space suits or the health care personnel who should wear them for the prevention of surgical

site infection in prosthetic joint arthroplasty. (No recommendation/unresolved issue) 168-170

(Key Question 18)

VI. POSTOPERATIVE AMP DURATION WITH DRAIN USE

19. In prosthetic joint arthroplasty, Recommendation 1E applies: In clean and cleancontaminated procedures, do not administer additional prophylactic antimicrobial agent doses 

after the surgical incision is closed in the operating room, even in the presence of a drain. 

(Category IA) 27-65 (Key Question 19)

VII. BIOFILM

20A. No recommendation can be made regarding the safety and effectiveness of cement 

modifications and the prevention of biofilm formation or surgical site infection in prosthetic 

joint arthroplasty. (No recommendation/ unresolved issue)

171,172 (Key Question 20A)

20B. No recommendation can be made regarding the safety and effectiveness of prosthesis 

modifications for the prevention of biofilm formation or surgical site infection in prosthetic joint 

arthroplasty. (No recommendation/unresolved issue) (Key Question 20B)

20C. No recommendation can be made regarding the safety and effectiveness of vaccines for 

the prevention of biofilm formation or surgical site infection in prosthetic joint arthroplasty.

(No recommendation/unresolved issue) (Key Question 20C)
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

16

20D. No recommendation can be made regarding the safety and effectiveness of biofilm control 

agents such as biofilm dispersants, quorum-sensing inhibitors, or novel antimicrobial agents for 

the prevention of biofilm formation or surgical site infection in prosthetic joint arthroplasty. 

(No recommendation/unresolved issue) (Key Question 20D)
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

17

III. Background

In 2006, approximately 80 million surgical procedures were performed in United States (U.S.)

inpatient hospital (46 million)4and ambulatory hospital-affiliated or free-standing (32million)

settings.3 Between 2006 and 2009, SSIs complicated approximately 1.9% of surgical procedures 

in the United States.

173 However, the number of SSIs is likely to be underestimated given that 

approximately 50% become evident after discharge.

2

 From January 2009 through December 

2010, SSIs accounted for 23% of 69,475 healthcare-associated infections (HAIs) reported to the 

Centers for Disease Control and Prevention’s (CDC) National Healthcare Safety Network (NHSN)

surveillance system by 2,039 hospitals.

174

 An attempt to establish a national surveillance 

definition for SSI175 has not been widely adopted in the scientific literature, which in 

combination with inconsistencies in coding and a lack of standardization of post-discharge 

surveillance, has made it challenging to evaluate or compare interventions and track SSIs over 

time.

5

Multiple patient co-morbidities and risk factors, in addition to procedure-related risk factors,

can impact the risk of SSI.

5

 SSIs result in increased morbidity, mortality, and direct and indirect 

costs including increased hospital length of stay, readmissions for treatment including repeat 

surgical procedures, outpatient and emergency care visits, use of ancillary services, additional 

medications (including prolonged antimicrobial therapy), lost productivity, and temporary or 

permanent disability.

176 Actual attributable costs of SSIs are difficult to determine. Cost 

estimates are commonly restricted to hospital charges and vary according to surgical 

procedure, depth of infection, facility, region, country, publication year, study design, and 

accounting method.

176-178

 Estimated average attributable costs of SSIs range from $10,443 to 

$25,546 per infection (2005 and 2002 dollars, respectively).

6-8,179

 Staphylococcus aureus and 

coagulase negative staphylococci are the organisms most commonly associated with SSIs, but 

pathogens can vary by procedure.

174

 Costs can exceed $90,000 per infection when the SSI 

involves a prosthetic joint implant180,181 or antimicrobial resistant organism.

182

In 2002 CDC and Centers for Medicare & Medicaid Services (CMS) instituted the Surgical 

Infection Prevention (SIP) project with the goal of reducing SSIs. 

183

 In 2006, SIP became the 

Surgical Care Improvement Program (SCIP) and expanded to include patient hair removal at the 

surgical site, glycemic control, and normothermia process measures.

184

 With the Deficit 

Reduction Act of 2005, the U.S. Congress set forth a mandate for hospital reporting of process, 

outcome, and other quality improvement measures and for making this information available 

to the public and CMS.

11

 In addition, this act required CMS to adjust payments downward for 

HAIs that could have been prevented through the application of evidence-based strategies. In 

2009, the U.S. Department of Health and Human Services' National Action Plan to Prevent 

Health Care-Associated Infections: Road Map to Elimination set a 5-year target goal of a 25% 

reduction in SSIs detected on admission and readmission or a 0.75 Standardized Infection Ratio 

(SIR).

9

Since January of 2012, CMS’s Hospital Inpatient Quality Reporting Program has required 

facilities to report SSI outcome data through CDC’s NHSN.

10

 Between 2009 and 2010 improved 

prevention of deep incisional and organ/space SSIs detected on admission and readmission was 

documented for coronary artery bypass graft (CABG), total knee arthroplasty (TKA), and colon 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

18

surgical procedures (18%, 11%, and 9% relative risk reduction of SSIs, respectively).

185

 

Approximately 55% of SSIs are deemed preventable by application of evidence-based 

strategies.

179

 

Prosthetic joint arthroplasty

Prevention efforts should target all surgical procedures, but especially those where both human 

and financial burden is greatest. In 2011, primary TKAs accounted for over half of the 1.2 

million prosthetic joint arthroplasty procedures (primary and revision) performed in the United 

States, followed by total hip arthroplasty (THA), and hip hemi-arthroplasties.

186

 Primary 

shoulder, elbow, and ankle arthroplasties are much less common. By 2030, prosthetic joint 

arthroplasties are projected to increase to 3.8 million procedures per year.187-189

Infection is the most common indication for revision in TKA190 and the third most common

indication in THA,

190 following instability/dislocation and mechanical loosening. S. aureus and 

coagulase negative staphylococci are the most common pathogens associated with orthopaedic 

SSI.

174 Between 2001 and 2009, there was a significant increase in the risk of infection 

following hip and knee arthroplasties (from 1.99% to 2.18% and from 2.05% to 2.18%, 

respectively).

181 By 2030 the infection burden for hip and knee arthroplasty is expected to 

increase to 6.5% and 6.8%, respectively.

191 Owing to both increasing risk and the number of 

individuals undergoing prosthetic joint arthroplasty procedures, between 2010 and 2020, the 

total number of hip and knee prosthetic joint infection (PJI) cases is projected to increase from

25,000 to 70,000 and up to 221,500 cases per year by 2030.

181,191 Treatment of PJI commonly 

involves a 2-stage procedure, with 4 to 8 weeks of parenteral antimicrobial therapy between 

stages. When eradication of the infection is not possible, treatment can include arthrodesis or 

even amputation.192 In 2009 the average hospital cost for the revision of an infected hip or 

knee arthroplasty was $93,600 and $24,200, respectively.

181 Between 2001 and 2009, 

estimated total hospital costs for treating PJI increased from $320 million to $566 million, and is

projected to reach $1 billion by 2014 and $1.62 billion by 2020.

181

Any indwelling medical device or prosthetic implant has the potential to become colonized by 

organisms embedded in biofilm.

193,194

 In the United States, as many as 13 million people 

experience a biofilm-related infection every year.

195 Biofilm is defined as “a microbially derived 

sessile community characterized by cells that are irreversibly attached to a substratum or 

interface or to each other, are embedded in a matrix of extracellular polymeric substances that 

they have produced, and exhibit an altered phenotype with respect to growth rate and gene 

transcription”.

194 Biofilm organisms exhibit significant resistance to antimicrobial agents (10 to 

1000 times the minimum inhibitory concentration [MIC]) as compared to their free floating, 

planktonic counterparts.194 Mechanisms involved in this increased antimicrobial resistance may 

include: “...delayed penetration of the antimicrobial agent through the biofilm matrix, altered 

growth rate of the biofilm organisms, and other physiologic changes due to the biofilm mode of 

growth”.194 Between 7% and 39% of PJIs are culture negative,

196,197 which is often attributed to 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

19

previous antimicrobial therapy198 or the presence of difficult to culture biofilm organisms,

making diagnosis, treatment, and the identification of prevention measures critical. 

Evidence-based guidelines have provided recommendations for the diagnosis of PJI using 

conventional testing techniques including serologic and synovial fluid markers, tissue 

histopathology, traditional culture-based techniques, and imaging studies.

199 Recently 

published studies further support or add to these recommendations.

197,198,200-202 Potential 

future strategies for the diagnosis of PJI include the use of novel serologic203-207 and synovial 

fluid208 markers. In addition, novel strategies to improve the recovery of biofilm organisms may 

enhance detection of organisms present in lower numbers or species present as a minority.

193

 

Sonication of the explanted prosthesis197,209-212 or cement spacer211 produces a diluent of 

released biofilm sonicate. Culture of sonicate effluent may have improved culture sensitivity as 

compared to standard synovial fluid or tissue culture techniques. Different growth media197,213

and microscopic197,213-217 techniques to better grow and characterize biofilm and the embedded 

organisms are also being explored. Adjunct molecular techniques hold the potential to improve 

the sensitivity and specificity of traditional culture-based techniques.

213-215,217-223 However, only 

culture-based techniques provide information on antimicrobial susceptibility, which drives PJI 

treatment, therefore exploring ways to enhance culturing techniques continues to be 

important.

224 Multidisciplinary work to standardize the clinical diagnosis of PJI is ongoing. 225
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

20

IV. Scope and Purpose

This guideline provides updated and new recommendations for the prevention of SSI. This 

guideline does not provide comprehensive infection control recommendations for prevention 

of SSIs. The select areas of focus were informed by feedback received from clinical experts and 

input from the Healthcare Infection Control Practices Advisory Committee (HICPAC), a federal 

advisory committee to the Centers for Disease Control and Prevention (CDC). As in the 

Guideline for Prevention of Surgical Site Infection, 1999 this guideline does not specifically 

address SSI prevention issues unique to: burns, trauma, surgical incisions allowed to heal by 

secondary intention, transplant procedures, transmission of blood borne pathogens from 

healthcare personnel to the patient, pediatric surgical practice, minimally invasive procedures, 

procedures performed outside of the operating room (e.g., endoscopic procedures), nonsurgical invasive procedures (e.g., cardiac catheterization, interventional radiology) and other 

procedures or conditions not specifically mentioned.

12

 In general, SSI prevention measures 

deemed effective in adults are also indicated in the pediatric surgical population, and those 

effective in the operating room can be adapted or modified for other settings. In addition, this 

update does not address SSI surveillance or public reporting.

1,2

Recommendations on infection 

control in healthcare personnel,

13

 environmental infection control,

14 and disinfection and 

sterilization of medical devices15 in health care settings are topics addressed by other 

guidelines. 

To evaluate the evidence on SSI prevention, key questions addressing 13 intervention 

categories were examined. Six topics evaluated the literature across all surgical procedures 

and comprise the Core section of the guideline: Parenteral antimicrobial prophylaxis, Nonparenteral antimicrobial prophylaxis, Glycemic control, Normothermia, Oxygenation, and 

Antiseptic prophylaxis. Seven other topics evaluated the literature specific to Prosthetic Joint 

Arthroplasty and comprise the second section: Blood transfusions, Systemic 

immunosuppressive therapy, Intra-articular corticosteroid injections, Anticoagulation, 

Orthopaedic space suit, Postoperative antimicrobial prophylaxis duration with drain use, and 

Biofilm. The specific key questions were:

CORE SECTION

Parenteral antimicrobial prophylaxis (AMP)

Q1. What are the most effective strategies for administering parenteral AMP to reduce the risk 

of SSI? 

Non-parenteral Antimicrobial prophylaxis

Q2. What are the most effective strategies for administering non-parenteral antimicrobial 

prophylaxis at the surgical incision to reduce the risk of SSI?

Glycemic control

Q3. How do perioperative blood glucose and hemoglobin A1C levels impact the risk of SSI, and 

what are their optimal perioperative target levels in diabetic and non-diabetic patients?
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

21

Normothermia

Q4. How safe and effective is the maintenance of perioperative normothermia in reducing the 

risk of SSI? 

Q5. What are the most effective strategies for achieving and maintaining perioperative 

normothermia? 

Oxygenation

Q6. In patients with normal pulmonary function, how safe and effective is the perioperative use 

of increased fraction of inspired oxygen (FiO2) in reducing the risk of SSI?

Q7. What is the optimal target FiO2 to reduce the risk of SSI; how and when should it be 

administered?

Antiseptic prophylaxis

Q8. What are the most effective strategies for preparing the patient’s skin prior to surgery to

reduce the risk of SSI?

Q9. How safe and effective is antiseptic irrigation prior to closing the surgical incision?

Q10. How safe and effective is repeat application of antiseptic skin preparation agent to the 

surgical site immediately prior to closing the surgical incision?

PROSTHETIC JOINT ARTHROPLASTY SECTION

Blood transfusion

Q11. How do perioperative blood transfusions impact the risk of SSI in prosthetic joint 

arthroplasty patients? 

Systemic immunosuppressive therapy

Q12. How does systemic corticosteroid or other immunosuppressive therapy impact the risk of 

SSI in prosthetic joint arthroplasty patients? 

Q13. What are the most effective strategies in managing systemic corticosteroid or other 

immunosuppressive therapy perioperatively to reduce the risk of SSI in prosthetic joint 

arthroplasty patients?

Q14. What is the optimal duration of postoperative AMP to reduce the risk of SSI in prosthetic 

joint arthroplasty patients on systemic corticosteroid or other immunosuppressive therapy?

Intra-articular corticosteroid injections

Q15. How do preoperative intra-articular corticosteroid injections impact the risk of SSI in 

prosthetic joint arthroplasty patients?

Q16. What are the most effective strategies for managing the preoperative use of intraarticular corticosteroid injections to reduce the risk of SSI in prosthetic joint arthroplasty 

patients?
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

22

Anticoagulation

Q17. What are the most effective strategies for managing perioperative venous 

thromboembolism (VTE) prophylaxis to reduce the risk of SSI?

Orthopaedic space suit

Q18. How safe and effective are orthopaedic space suits in reducing the risk of SSI in prosthetic 

joint arthroplasty patients, and which healthcare personnel should wear them?

Postoperative antimicrobial prophylaxis duration with drain use

Q19. What is the optimal duration of postoperative AMP to reduce the risk of SSI in prosthetic 

joint arthroplasty in the presence of a drain?? 

Biofilm

Q20. What are the most effective strategies to reduce the risk of biofilm formation and SSI in 

prosthetic joint arthroplasty?

Evidence-based recommendations were cross-checked with those from other guidelines 

identified in an initial systematic search. 

This document is intended for use by surgeons, physician assistants, perioperative nurses and 

other allied perioperative assistive personnel, anesthesia providers, postoperative inpatient and 

clinic nurses, infection prevention staff, healthcare epidemiologists, healthcare administrators, 

other healthcare providers, and persons responsible for developing, implementing, delivering, 

and evaluating infection prevention and control programs for surgical procedures performed in 

an operating room (inpatient or ambulatory setting). The guideline can also be used as a 

resource for professional societies or organizations that wish to develop more detailed 

implementation guidance or to identify future research priorities where there are evidence 

gaps for the prevention of SSI. 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

23

V. Methods

This guideline was based on a systematic review of the best available evidence on SSI

prevention. The Grading of Recommendations Assessment, Development and Evaluation 

(GRADE) approach was used to assess the quality of the available evidence, the strength of 

resulting the recommendations, and to provide explicit links between thems.

16-19 The guideline 

development process has been previously described.

21 Methods and details that were unique 

to this guideline are included below.

Development of Key Questions

A preliminary list of key questions was developed from a review of the 1999 CDC SSI 

guideline.

12

 Content experts were surveyed to provide feedback on the questions and identify 

additional topics of interest. Key questions were put in final form after vetting them with a 

panel of content experts and HICPAC members. 

Literature Search

Following the development of the key questions, search terms were developed for identifying 

literature most relevant to those questions. For the purposes of quality assurance, these terms 

were compared to those used in relevant seminal studies and guidelines. These search terms 

were then incorporated into search strategies for the relevant databases. Searches were 

performed in MEDLINE, EMBASE, CINAHL, and the Cochrane Library. All databases were 

searched from 1998, when the previous guideline searches ended, through June 2011 for the 

Core section and December 2011 for the Prosthetic Joint Arthroplasty Section. References 

were imported into a reference manager where duplicates were resolved. The detailed search 

strategy and results for the Core section can be found in Appendix 1 and for the Prosthetic 

Joint Arthroplasty section in Appendix 2.

Study Selection

Titles and abstracts were screened by one independent reviewer (S.I.B.T., R.K., or C.R.). A 

random sample of 10% of titles and abstracts had a second independent review to ensure 

consistency in screening. Kappa scores, used to measure agreement between the two 

independent reviewers beyond chance, ranged from 0.4 – 0.5, indicating “moderate 

agreement” between reviewers.

226 Full text articles were retrieved if they were: 1) relevant to 

one or more key questions; 2) clinical practice guidelines, systematic review (SRs) or primary 

study designs meeting the inclusion criteria (randomized control trial [RCTs] for the Core and 

Prosthetic Joint Arthroplasty sections and observational [OBS] studies for the Prosthetic Joint 

Arthroplasty section because none of that section’s key questions were adequately addressed 

by results from the initial search); 3) written in English; and 4) available as full text studies 

(meeting abstracts were excluded). Animal studies and in vitro basic science studies were 

excluded from all topics except Biofilm. Pediatric patient studies were included. Although the 

literature databases were searched from 1998 to 2011, studies published earlier than 1998 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

24

were eligible for inclusion (e.g., studies suggested by the expert panel, included in the previous 

guideline or in published SRs). 

Full-text articles were screened by two independent reviewers (S.I.B.T and R.K. or S.I.B.T. and 

C.R.) and disagreements were resolved by discussion. Full-text articles were excluded if: 1) SSI

was not reported as an outcome; 2) all patients included had “dirty” surgical procedures 

(except for Q2 addressing the use of aqueous iodophor irrigation); 3) the study only included 

oral medicine or dental health procedures; 4) the surgical procedures did not include primary 

closure of the incision in the operating room (e.g. orthopedic pin sites, thoracotomies, or 

percutaneous endoscopic gastrostomy (PEG) procedures, or wounds healing by secondary 

intention); or 5) the study evaluated wound protectors used post incision. For the Core section, 

Q1 Parenteral antimicrobial prophylaxis, studies comparing the efficacy of antimicrobial 

prophylaxis to no prophylaxis (placebo-controlled studies) and studies comparing the efficacy of 

different prophylactic antimicrobial agents were excluded. Also for Q2 Non-parenteral 

antimicrobial prophylaxis, use of gentamycin collagen sponge studies (not approved by the 

Food and Drug Administration [FDA])were excluded. For Q8-10 Antiseptic prophylaxis, studies 

evaluating vaginal antisepsis in combination with abdominal antisepsis were excluded. In 

addition, studies using electrolyzed ionized solution (not approved by the Food and Drug 

Administration [FDA] for intraoperative irrigation of the surgical site) and dry povidone iodine 

powder spray studies were excluded. For the Prosthetic Joint Arthroplasty section, studies 

were excluded if they did not specifically examine prosthetic joint arthroplasties. Questions 

from four topics in the Prosthetic Joint Arthroplasty section were excluded from a targeted 

search when both: 1) the initial broad search identified very few or no RCTs or SRs that fit the 

inclusion criteria and 2) the content experts excluded them as priority topics and/or key 

questions (i.e., Surgical attire- gloves, Surgical techniques, Anesthesia, and Environmental 

factors). Also, questions and related studies addressing diagnosis of PJI or biofilm were 

excluded because they did not address SSI prevention. Special inclusion criteria for the Core 

section were: for Q1, studies on the optimal timing of AMP in cesarean sections; for Q2 

autologous platelet rich plasma gel; for Q9 and Q10 aqueous iodophor solution irrigation or 

repeat application to skin prior to closing the surgical incision. Special inclusion criteria for the 

Prosthetic Joint Arthroplasty section included: for Q11 Blood transfusion- studies that 

evaluated the administration of epoetin alpha in combination with blood transfusion.

A draft bibliography was shared with a panel of content experts and additional suggested 

references then progressed through title/abstract and full text review as above. Results of the 

entire study selection process are depicted in Figure 1.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

25

Figure 1. Results of the Study Selection Process 

43 RCTs identified from excluded SRs

133 studies extracted into evidence 

and GRADE tables

4,961 potentially relevant 

studies identified in 

literature searches

168 studies cited in 

1999 CDC SSI 

guideline

5,233 title/abstracts screened

4,436 studies excluded

797 full text review

682 studies excluded

564: not relevant to key questions 

108: study design 

6: not available as full text article 

4: not in English

25 clinical practice guidelines

14 additional 

clinical practice 

guidelines 

identified by 

writing group 

23 clinical practice guidelines

cited in current guideline

16 clinical practice 

guidelines excluded

104 studies 

suggested by 

content experts
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

26

Data Extraction and Synthesis

For studies meeting the inclusion criteria, data on the study author, year, design, risk of bias, 

objective, population, setting, sample size, interventions, and results of clinically relevant 

outcomes were extracted into standardized evidence tables. From these, evidence tables were 

developed for each clinical topic represented by the key questions. Studies were extracted into 

the most relevant evidence table. Studies were organized by individual key questions and 

subquestions. Data were extracted by a single author (S.I.B.T., E.C.S., B.L., or R.A.) and crosschecked by another author (S.I.B.T.). Disagreements were resolved by the remaining authors. 

Data and analyses were extracted as originally presented in the included studies. Metaanalyses were performed only where their use was deemed critical to a recommendation and 

only in circumstances in which multiple studies with sufficiently homogenous populations, 

interventions, and outcomes could be analyzed. The risk of bias associated with each study was 

assessed using scales developed by the Penn Medicine Center for Evidence-based Practice, and 

scores were recorded in the evidence tables. Appendices 1 and 2 include the questions used to 

assess the risk of bias of the included SRs, RCTs, and OBS for the Core and Prosthetic Joint

Arthroplasty Sections, respectively. 

Systematic reviews were included in this review if the individual studies in the review fit our 

inclusion criteria. To avoid duplication of data, primary studies identified by our search were 

excluded if they were also included in a systematic review captured in our search. The 

exception to this was 1) if the primary study also addressed a relevant question that was 

outside the scope of the included systematic review or 2) if it was one of a select number of 

studies in the systematic review that fit our inclusion criteria and was used to perform a new 

meta-analysis. Systematic reviews that analyzed primary studies that were fully captured in a 

more recent systematic review were excluded. The only exception to this was if the older 

systematic review also addressed a relevant question that was outside the scope of the newer 

systematic review.

227

To ensure that all relevant studies were captured in the search, the bibliography was vetted by 

a panel of content experts. Statistical analyses were performed using Review Manager 5.1. 

For the purposes of our review, statistical significance was defined as p≤0.05. 

For all other methods (i.e., Grading of Evidence, Formulation of Recommendations, and 

Finalizing of the Guideline) please refer to the Guideline Methods supplement.21

Reviewing and Finalizing the Guideline

The writing group completed a draft of the guideline, including evidence reviews,

recommendations, evidence tables, and GRADE tables, and shared it with the expert panel for 

in depth review. Based on the expert panel’s feedback, the writing group revised the guideline 

documents and presented draft recommendations to HICPAC at public meetings for their 

review and input. Following further revisions, CDC then submitted the guideline for an initial 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

27

clearance at CDC and is posting it in the Federal Register for a period of public comment. After 

this period of public comment, the comments will be reviewed at a HICPAC meeting, revised 

accordingly, and the final guideline will be submitted to CDC for final clearance. Once cleared, 

the guideline will be posted to CDC’s website and published.

Updating the Guideline

Revisions to this guideline will be guided by new research and technological advancements for 

preventing SSIs.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

28

VI. Evidence Review: Core section

PARENTERAL ANTIMICROBIAL PROPHYLAXIS (AMP)

Q1. What are the most effective strategies for administering parenteral AMP to 

reduce the risk of SSI? 

To answer this question, we focused on five subquestions: A) What is the optimal timing of 

preoperative AMP? B) What is the optimal timing of AMP in cesarean section: prior to skin 

incision or at cord clamping? C) How safe and effective is weight-adjusted AMP dosing? D) How 

safe and effective is intraoperative redosing of AMP? and E) How safe and effective is 

postoperative AMP and what is the optimal duration? 

Q1A. What is the optimal timing of preoperative AMP?

Our search did not identify RCTs or SRs that evaluated different timings of preoperative AMP 

administration and its impact on the risk of SSI.

Other Guidelines

The 1999 CDC Guideline for Prevention of Surgical Site Infection and other clinical practice 

guidelines, based on a review of the evidence and expert opinion, recommend administering by 

the intravenous route a single dose of prophylactic antimicrobial agent only when indicated. 

For most prophylactic agents, the 1999 CDC guideline recommended preoperative 

administration be timed such that a bactericidal concentration of the drug is established in the 

serum and tissues when the incision is made and now other clinical practice guidelines 

recommend that administration should be within 60 minutes prior to incision (vancomycin and 

fluoroquinolones within 60-120 minutes prior to incision).

12,183,228-232 None of the 

recommendations address whether it is necessary to administer a complete or a partial infusion 

of the parenteral AMP dose prior to surgical incision. 

Q1B. What is the optimal timing of AMP in cesarean section: prior to skin 

incision or at cord clamping?

The available data on optimal timing of antimicrobial prophylactic agent administration in 

cesarean section examined AMP administered prior to skin incision versus at cord clamping.

For this comparison we considered post-partum endometritis as the critical outcome. Incisional 

SSI, neonatal sepsis, neonatal sepsis workup, and neonatal intensive care unit (NICU) admission 

outcomes were also evaluated. In general, endometritis was defined as fever > 100.4○F on two 

occasions with uterine tenderness, purulent lochia, tachycardia or leukocytosis. The findings of 

the evidence review and the grades for all important outcomes are shown in Evidence Review 

Table 1B.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

29

High-quality evidence suggested a benefit of AMP administration prior to skin incision as

compared to administration immediately after the umbilical cord is clamped in cesarean 

sections. This was based on a SR22 (low risk of bias) with a meta-analysis (N=749) of 3 RCTs23-25

suggesting a 53% reduction in post-partum endometritis and no difference in proven neonatal 

sepsis or neonatal sepsis workups. High-quality evidence from a meta-analysis (N=681 

neonates) of 2 studies suggested no difference in NICU admissions.

23,24 One study suggested 

significantly shorter NICU stays and no difference in neonatal sepsis causative organisms with 

administration of AMP prior to skin incision.

23

Other Guidelines

Clinical practice guidelines based on a review of the evidence and expert opinion recommend 

administration of a single preoperative prophylactic antimicrobial agent by the intravenous 

route, based on the agent pharmacokinetics, commonly beginning within 60 minutes prior to 

skin incision in both elective and emergency cesarean section.228-230,232 Administration of AMP 

after cord clamping is no longer recommended.

12

Q1C. How safe and effective is weight-adjusted AMP dosing?

Our search did not identify RCTs or SRs that evaluated weight-adjusted AMP dosing and its 

impact on the risk of SSI. 

Other Guidelines

Clinical practice guidelines based on a review of the evidence and expert opinion recommend 

increasing the single preoperative prophylactic antimicrobial agent dose for select prophylactic 

antimicrobial agents in obese and morbidly obese patients.

228-232 For cefazolin,

recommendations are to administer 2g229-231 for patients weighing >60-80kg and 3g230 if 

>120kg. For aminoglycosides, dosing is calculated using the patient’s ideal body weight plus 

40% of the difference between the actual and ideal body weight.

230,233 Vancomycin should be 

dosed at 15mg/kg.

229-231

Q1D. How safe and effective is intraoperative redosing of AMP? 

The available data examining intraoperative redosing of AMP compared one preoperative dose 

versus one preoperative dose plus an additional dose at 2 hours intraoperatively.

For this comparison we considered abdominal and perineal wound SSI and intra-abdominal 

abscess as the outcomes of interest. Antimicrobial resistance outcome was also evaluated. 

The evidence for this question consists of 1 RCT at moderate risk of bias in elective colorectal 

surgery.

26 The findings of the evidence review and the grades for all important outcomes are 

shown in Evidence Review Table 1D.

Moderate-quality evidence suggested no benefit of intraoperative AMP redosing. This was 

based on no difference in abdominal or perineal wound infection, intra-abdominal abscess, or 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

30

antimicrobial resistance in 1 elective colorectal surgery study from 1991.

26 However, 

procedures with durations >3 hours had a significantly higher risk of SSI and 22% of patients 

with procedure durations ≥2 hours were not redosed. Fecal contamination almost doubled the 

SSI rate at every level of contamination (of note, patients underwent mechanical bowel prep 

alone). Procedure duration and fecal contamination were not reported by study group. 

Limited power of the study could result in a false negative finding. 

Other Guidelines

Clinical practice guidelines based on a review of the evidence and expert opinion recommend

prophylactic antimicrobial agent redosing in cases of prolonged procedures (when the 

procedure exceeds the half-life of the prophylactic antimicrobial agent or is longer than 3-4 

hours) and in patients with major blood loss (>1500 ml) or extensive burns.229-232,234 Redosing 

should also be performed at intervals of 1-2 times the prophylactic antimicrobial agent half-life, 

starting at the beginning of the preoperative dose.

229-232,234 No recommendations are provided 

for optimal prophylactic antimicrobial agent dosing in obese and morbidly obese patients when 

redosing.

Q1E. How safe and effective is postoperative AMP and what is the optimal 

duration?

To answer this question, we focused on studies that used the same prophylactic antimicrobial 

agent in both arms. We evaluated administration of postoperative AMP both with all surgical 

procedures combined and by select surgical specialties. Studies that compared different 

prophylactic antimicrobial agents or those administering only oral AMP were excluded. We 

defined postoperative AMP as any parenteral prophylactic antimicrobial agent administered 

after intraoperative closure of the surgical incision. Therefore, postoperative AMP (in hours or 

days), does not include any AMP administered as a single preoperative dose, and/or any 

intraoperative redosing. 

The available data examined the following comparisons for different postoperative AMP 

durations:

1. All surgeries - None vs. ≤24 hours

2. Cardiac 

a. None vs. ≤24 hours

b. None vs. 72-96 hours

3. Thoracic - None vs. 2 days

4. Vascular 

a. None vs. ≤24 hours

b. <24 hours vs. 3-5 days

c. None vs. 5 days

5. Ear, nose, and throat - ≤24 hours vs. 3-5 days

6. Gynecologic
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

31

a. None vs. ≤24 hours

b. <24 hours vs. <2.5 days

7. Orthopaedic

a. Fracture - None vs. ≤24 hours

b. Prosthetic Joint Arthroplasty - None vs. ≤24 hours

8. Colorectal: Bowel preparation with oral antimicrobials

a. None vs. 3 days 

b. ≤24 hours vs. 5 days

9. Colorectal: Bowel preparation only

a. None vs. ≤24 hours 

b. None vs. <2-3 days 

10. Colorectal: Bowel preparation not reported

a. None vs. ≤24 hours 

b. ≤24 hours vs. 2-3 days 

11. Colorectal: No bowel preparation

a. None vs. ≤24 hours 

b. None vs. <2-3 days 

12. Appendectomy

a. None vs. ≤24 hours

b. None vs. 2 days

13. Rectal surgery- None vs. ≤24 hours

14.Gastric surgery

a. None vs. ≤24 hours

b. None vs. 4 days

15. Hepatectomy – 2 days vs. 5 days

For all comparisons, we considered SSI (superficial, deep incisional, and organ/space) and trocar 

wound infection as the critical outcomes. Antimicrobial resistance, adverse events, length of 

stay, mortality, and pharyngocutaneous fistula outcomes were also evaluated. The evidence 

for this question consists of 39 RCTs in cardiac,

27-30 thoracic,31 vascular,32-34 ear, nose and 

throat,

35,36 gynecologic,37-41 orthopaedic,42-47 and general surgical48-65 procedures. Twenty-eight 

(72%) studies were published between 1972 and 1998; 11 (28%) studies were published 

between 2003 and 2011. The findings of the evidence review and the grades for all important 

outcomes are shown in Evidence Review Table 1E.

Q1E.1. All surgeries - None vs. ≤24 hours

High-quality evidence suggested no benefit of continuing AMP after intraoperative closure of 

the surgical incisions. This was based on no difference in SSI in 1 large meta-analysis 

(N=13,408) of 19 RCTs in cardiac, thoracic, vascular, ear, nose and throat, gynecologic, 

orthopaedic, and general surgical procedures.

27,32,37-40,42-47,50-53,57,62,63 Fourteen (74%) studies 

were published between 1984 and 1995; 5 were published between 2005 and 2008. Results by
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

32

select surgical specialties or procedures and individual comparators are available in the GRADE 

table.

Q1. Recommendations

1A. Administer preoperative antimicrobial agent only when indicated, based on published 

clinical practice guidelines and timed such that a bactericidal concentration of the agent is 

established in the serum and tissues when the incision is made (Category IB) 12 (Key Question 

1A)

 No further refinement of timing can be made for preoperative antimicrobial agent 

based on clinical outcomes. (No recommendation/unresolved issue) (Key Question 1A)

1B. Administer the appropriate parenteral prophylactic antimicrobial agent prior to skin incision 

in all cesarean sections. (Category IA) 22-25 (Key Question 1B)

1C. No recommendation can be made regarding the safety and effectiveness of weight-adjusted 

dosing of parenteral prophylactic antimicrobial agents for the prevention of surgical site 

infection. (No recommendation/unresolved issue) (Key Question 1C)

1D. No recommendation can be made regarding the safety and effectiveness of intraoperative 

redosing of parenteral prophylactic antimicrobial agents for the prevention of surgical site 

infection. (No recommendation/unresolved issue) 26 (Key Question 1D)

1E. In clean and clean-contaminated procedures, do not administer additional prophylactic 

antimicrobial agent doses after the surgical incision is closed in the operating room, even in the 

presence of a drain. (Category IA) 27-65 (Key Question 1E)

NON-PARENTERAL ANTIMICROBIALPROPHYLAXIS

Q2. What are the most effective strategies for administering non-parenteral 

antimicrobial prophylaxis at the surgical incision to reduce the risk of SSI?

To answer this question we focused on four subquestions: A) How safe and effective is 

antimicrobial irrigation? B) How safe and effective are antimicrobial agents applied to the 

surgical incision? C) How safe and effective are antimicrobial-coated sutures, when and how 

should they be used? and D) How safe and effective are antimicrobial dressings applied to the 

surgical incision following primary closure in the operating room?

2A. How safe and effective is antimicrobial irrigation?
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

33

Our search did not identify RCTs or SRs that evaluated the safety and effectiveness of 

antimicrobial irrigation or the soaking of surgical implants (e.g., meshes, neurosurgical 

ventricular shunts) in antimicrobial solution prior to insertion (in combination with parenteral 

AMP) and its impact on SSI. 

Other Guidelines

One clinical practice guideline, based on a review of the evidence, recommends against 

antimicrobial wound irrigation or intra-cavity lavage to reduce the risk of SSI.234

Q2B. How safe and effective are antimicrobial agents applied to the surgical 

incision?

The available data examined the following comparisons:

1. Ampicillin vs. No topical antimicrobial agent

2. Chloramphenicol vs. No topical antimicrobial agent

3. Rifampin vs. No topical antimicrobial agent

4. Autologous platelet rich plasma (APRP) (spray or gel) vs. No APRP

For all comparisons, we considered SSI the critical outcome. Wound dehiscence and wound 

closure outcomes were also evaluated. The evidence for the pharmacologic antimicrobial 

prophylactic agent comparators consists of 1 SR66 and 2 RCTs67,68 and for the APRP comparator 

3 RCTs73-75. APRP provides a platelet concentrate commonly used to enhance both, wound 

hemostasis (formation of a fibrin clot) and wound healing (clot provides a matrix for the 

migration of tissue-forming cells and endothelial cells involved in angiogenesis and remodeling 

of the clot into repair tissue).

235,236 These characteristics have led to a significant increase in the 

use of APRP therapies for the treatment of chronic wounds and multiple orthopaedic conditions 

including bone repair, tendon, and soft tissue injuries.

237,238 In addition, in vitro studies have 

demonstrated that APRP holds strong bactericidal activity, and suggested its potential value as 

an adjunct topical antimicrobial prophylactic agent for use at the time of surgical incision 

closure.

239,240In all studies, both groups received parenteral AMP. Our search did not identify 

RCTs or SRs that evaluated the safety and effectiveness of vancomycin powder for the 

prevention of SSI. The findings of the evidence review and grades for all important outcomes 

are shown in Evidence Review Table 2B.

Q2B.1. Ampicillin vs. no topical antimicrobial agent

High-quality evidence suggested no benefit of topical ampicillin solution or powder in 

combination with parenteral AMP. This was based on no difference in SSI in one SR’s66 metaanalysis (N=699) of 4 older (1985-1994) RCTs in clean-contaminated colorectal

70,71 and 

appendectomy69,72 procedures. 

Q2B.2. Chloramphenicol vs. no topical antimicrobial agent
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

34

Moderate-quality suggested no benefit of topical chloramphenicol ointment in combination 

with parenteral AMP. This was based on no difference in SSI in one small study at low risk of 

bias, in 92 hemi-arthroplasty or dynamic hip screw fixation procedures for hip fractures.

67

Q2B.3. Rifampin vs. no topical antimicrobial agent

Low-quality evidence suggested a benefit of topical rifampin in combination with parenteral 

AMP. This was based on a reduced risk of wound leakage, fewer local signs of inflammation, 

and reduced risk of wound dehiscence at the umbilical port site in one very small (N=48) 

laparoscopic cholecystectomy study at moderate risk of bias.

68 Umbilical port-site infection was 

defined as “purulent wound leakage”. Based on results reported in a histogram, 12 hours 

postoperatively, 71% of patients had purulent wound leakage including almost half of the 

rifampin and all of the control groups. By 24 hours the entire control group remained infected; 

a week later, only 2 infections remained. It is not clear if any of these were true infections.

Other Guidelines

Clinical practice guidelines based on a review of the evidence and expert opinion have 

recommendations both for231 and against234 the use of non-parenteral antimicrobials in the 

prevention of SSI. There are also strong recommendations against the use of antimicrobial 

ointments or creams on umbilical catheter insertion sites and other insertion sites, except for 

dialysis catheters, because of their potential to promote fungal infections and antimicrobial 

resistance.

241

Q2B.4. Autologous platelet rich plasma (spray or gel) vs. nothing

Moderate-quality evidence suggested no benefit of APRP spray or gel in combination with 

parenteral AMP. This was based on no difference in SSI in a meta-analysis (N=257) of 3 small 

RCTs: 2 studies in cardiac procedures (low73 and moderate74 risk of bias) and 1 study in TKA 

procedures75 (low risk of bias). Each individual study found no difference. The cardiac studies 

applied APRP spray73 or gel74 (produced using the same type of commercial platelet 

concentrate system) to the saphenous vein harvest site73,74 and/or the sternum74. The TKA 

study applied APRP spray (produced using a different platelet concentrate system than the 

cardiac studies) to the femoral and tibial cut bone surfaces and joint capsule followed by 

platelet poor plasma sprayed on the subcutaneous tissue. Moderate-quality evidence from this 

latter study suggested significantly increased risk of delayed total wound closure at 2 weeks 

postoperatively.

Q2C. How safe and effective are antimicrobial-coated sutures, when and how 

should they be used?

The available data examined antimicrobial-coated sutures (absorbable) versus nonantimicrobial-coated sutures (absorbable and non-absorbable) for the prevention of SSI.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

35

For this comparison we considered SSI the critical outcome. ASEPSIS score242, where points are 

given for “Additional treatment, the presence of Serous discharge, Erythema, Purulent exudate, 

and Separation of the deep tissues, the Isolation of bacteria, and the duration of inpatient 

Stay”, and product related adverse event outcomes were also evaluated. 

The evidence for this question consists of 4 RCTs.

76-79 The findings of the evidence review and 

grades for all important outcomes are shown in Evidence Review Table 2C.

High-quality evidence suggested no benefit of using antimicrobial coated sutures. This was 

based on no difference in SSI in a meta-analysis (N=420) of 4 RCTs and no product-related 

adverse events.

76-79 There was no difference in SSI among three small studies evaluating 

triclosan-coated suture in modified radical mastectomy (triclosan-coated suture subcuticular 

skin closure vs. Chinese silk suture interrupted transcutaneous skin closure)76 appendectomy 

for acute and ruptured appendicitis (abdominal sheath closure),

77 and pediatric general surgery

(level of closure not specified)79 procedures. One study79 at low risk for bias was designed to 

evaluate the surgeon’s assessment of intraoperative handling characteristics of the suture and 

another,

76 the cosmetic outcome, but not SSI as a primary outcome. Only one very small study 

(N=86) in predominantly pediatric patients undergoing cerebrospinal fluid shunt implantation 

or revision procedures suggested a reduction in risk of shunt infections with triclosan-coated 

suture closure of the galea and fascia.

78 This study also used plastic iodine-impregnated 

adhesive drapes, antimicrobial irrigation, and soaked the silicone shunt component in aqueous 

iodophor solution prior to implantation in both groups. Use of parenteral AMP was only 

reported for the appendicitis and cerebrospinal fluid shunt implantation studies. 

Q2D. How safe and effective are antimicrobial dressings applied to surgical 

incisions following primary closure in the operating room?

Our research did not identify RCTs or SRs that evaluated the safety and effectiveness of 

antimicrobial dressings (i.e., iodine, silver, or other antimicrobial ointment impregnated 

dressing) applied to surgical incisions closed primarily in the operating room (i.e., the skin edges 

are re-approximated at the end of the operation) and their impact on the risk of SSI.

12 Our 

search identified a SR of 16 RCTs evaluating various non-antimicrobial dressings.

243 This SR 

found no evidence to suggest that either covering the wound was effective or that any one nonantimicrobial dressing was more effective than another in reducing the risk of SSI in surgical 

incisions that were closed primarily in the operating room. This guideline does not address

prevention of SSI in trauma-related procedures, in surgical incisions left open to heal by 

secondary intention (i.e., left open in the operating room to be closed later, left open to heal by 

granulation, or which break open postoperatively) or burns. 

Q2. Recommendations
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

36

2A.1. No recommendation can be made regarding the safety and effectiveness of 

intraoperative antimicrobial irrigation (e.g., intra-abdominal, deep, or subcutaneous tissues) for 

the prevention of surgical site infection. (No recommendation/unresolved issue) (Key Question 

2A)

2A.2. No recommendation can be made regarding the safety and effectiveness of soaking 

prosthetic devices in antimicrobial solutions prior to implantation for the prevention of surgical 

site infection. (No recommendation/ unresolved issue) (Key Question 2A)

2B.1. Do not apply antimicrobial agents (i.e., ointments, solutions, powders) to the surgical 

incision for the prevention of surgical site infection (Category IB) 66-72 (Key Question 2B)

2B.2. Application of autologous platelet rich plasma is not necessary for the prevention of 

surgical site infection. (Category II)

73-75 (Key Question 2B)

2C. Use of antimicrobial coated sutures is not necessary for the prevention of surgical site 

infection. (Category II)

76-79 (Key Question 2C)

2D. No recommendation can be made regarding the safety and effectiveness of antimicrobial 

dressings applied to surgical incisions following primary closure in the operating room for the 

prevention of surgical site infection. (No recommendation/ unresolved issue) (Key Question 

2D)

GLYCEMIC CONTROL

Q3.How do perioperative blood glucose and hemoglobin A1C levels impact the 

risk of SSI, and what are their optimal perioperative target levels in diabetic and 

non-diabetic patients?

To answer this question we focused on two subtopics: A) Blood glucose and B) Hemoglobin 

A1C, their optimal perioperative target levels and the risk of SSI.

Q3A. Blood glucose and optimal perioperative target levels 

The available data examined strict versus standard blood glucose control in the prevention of 

SSI.

For this comparison we considered SSI and hypoglycemia as the critical outcomes. Each study 

reported a primary composite outcome variable that included SSI. Mortality and length of 

hospital stay, and surgical intensive care unit (SICU) stays were also evaluated in weighing the 

risks and benefits of perioperative glycemic control. The evidence for this question consists of 2 

RCTs in cardiac surgery patients with glycemic control protocols (intravenous, intensive insulin 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

37

therapy) instituted intraoperatively and continued in the SICU for 24-36 hours.80,81 Seventy to 

80% of patients in both of these studies are non-diabetics, highlighting the importance of 

glycemic control in both diabetic and non-diabetic surgical populations. The findings of the 

evidence review and the grades for all important outcomes are shown in Evidence Review Table 

3. 

Moderate-quality evidence suggested no benefit of strict (80-100mg/dL80 or 80-130mm/dL81) as 

compared to standard blood glucose target levels (<200mg/dL80 or 160-200mg/dL81) in diabetic 

and non-diabetic cardiac patients. This was based on no differences between groups for both a 

composite outcome variable and SSI in both studies. In Ghandi et al.,80 (N=371) the composite 

outcome variable included: death, sternal wound infections, prolonged pulmonary ventilation, 

cardiac arrhythmias, heart block requiring pacemaker or cardiac arrest, stroke or acute renal 

failure within 30 days postoperatively. In Chan et al.,81 (N=109) the composite outcome 

variable of infection included pneumonia, urinary tract infection, sepsis, septic shock, wound 

infection, bloodstream infection, and “catheter” infection (did not specify if venous or urinary).

High-quality evidence suggested no increased risk of hypoglycemia with strict blood glucose 

target levels. This was based on no differences between groups for number of hypoglycemic 

episodes in the SICU80 or ratio of hypoglycemic episodes per number of glucose 

measurements.

81

 Hypoglycemia definitions differed between studies: <60mg/dL in Ghandi and 

<50mg/dL in Chan. In Chan et al., while there was no difference between groups for the 

number of hypoglycemic episodes in the SICU, both groups reported a higher proportion of 

them there as compared to intraoperatively, suggesting the importance of continued close 

monitoring of glucose levels and the risk of hypoglycemic episodes in the postoperative period, 

even with standard glycemic control. No clinical complications resulting from hypoglycemia 

were reported at 30 days of follow up.

Other guidelines

While previous CDC guideline recommendations did not specify a perioperative blood glucose 

target level, they reported that in diabetics “increased glucose levels (>200mg/dL) in the 

immediate postoperative period (≤48 hours) were associated with increased risk of SSI”.

12

 

Blood glucose target level of <200mg/dL became standard clinical practice. Both studies 

reviewed in this guideline used <200mg/dL as the upper blood glucose target level.

80,81 Recently 

published professional society guidelines have recommended a slightly lower absolute serum 

blood glucose target level of <180mg/dL in diabetic244,245 and non-diabetic,

244 non-critically ill 

patients. In critically ill patients blood glucose target levels <150-180mg/dL246 and 140-

200mg/dL247 have been recommended. For terminally ill patients, those with limited life 

expectancy, or those at high risk for hypoglycemia, a blood glucose target level of 200mg/dL 

has been recommended.245 Intensive insulin therapy (blood glucose target levels of 80-

110mg/dl) to normalize blood glucose in the intensive care unit setting (surgical and medical) is 

not recommended in either diabetic or non-diabetic patients.

247

Q3B. Perioperative hemoglobin A1C and optimal target levels
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

38

Our search did not identify RCTs or SRs examining the association between hemoglobin A1C 

levels and risk of SSI.

Q3. Recommendations

3A.1. Implement perioperative glycemic control and use blood glucose target levels <200mg/dL 

in diabetic and non-diabetic patients. (Category IA) 80,81 (Key Question 3)

3A.2. No recommendation can be made regarding the safety and effectiveness of lower 

(<200mg/dL) or narrower blood glucose target levels, nor the optimal timing, duration, or 

delivery method of perioperative glycemic control for the prevention of surgical site infection. 

(No recommendation/unresolved issue) (Key Question 3)

3B. No recommendation can be made regarding optimal hemoglobin A1C target levels for the 

prevention of surgical site infection in diabetic and non-diabetic patients. (No 

recommendation/unresolved issue) (Key Question 3)

NORMOTHERMIA

Q4. How safe and effective is the maintenance of perioperative normothermia 

in reducing the risk of SSI? 

The available data examined the following comparisons:

1. Warming vs. no warming 

2. Warming: perioperative vs. intraoperative only

For all comparisons, we considered SSI the critical outcome. ASEPSIS score, mortality, blood 

loss, core temperature, length of hospital stay and duration of surgery outcomes were also 

evaluated. The evidence for this question consists of 3 RCTs.

82-84 The lower limit of 

normothermia has been inconsistently defined, ranging from a core temperature of 35.5○C to 

36○C. The findings of the evidence review and the grades for all important outcomes are shown 

in Evidence Review Table 4.

Q4A.1. Warming vs. no warming

High-quality evidence suggested a benefit of patient warming over no warming. This was based 

on a reduced risk of SSI in a meta-analysis (N=616) of 2 RCTs and reduced risk of ASEPSIS scores 

>20 with warming and maintenance of normothermia using various warming techniques in 

patients undergoing elective hernia repair, varicose vein surgery, and breast surgery 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

39

(preoperative warming)82 and elective colorectal surgery (intraoperative warming).

83

 

Normothermia was also associated with lower mean units of blood transfused per patient,

fewer patients transfused, and reduced hospital length of stay.

83 No difference in mortality was 

observed.

83

Q4A.2. Warming: perioperative vs. intraoperative only 

Moderate-quality evidence suggested a benefit of perioperative warming. This was based on 

reduced incidence of SSI with perioperative warming in 1 RCT of 103 patients undergoing 

elective major abdominal surgery.

84

Q4. Recommendation

4. Maintain perioperative normothermia (Category IA) 82-84 (Key Question 4)

Q5. What are the most effective strategies for achieving and maintaining 

perioperative normothermia? 

Our search did not identify RCTs or SRs that evaluated the most effective strategies for 

achieving and maintaining perioperative normothermia and their impact on the risk of SSI. 

Other Guidelines

Evidence-based clinical practice guidelines provide recommendations on perioperative 

management of normothermia including risk factor assessment, temperature monitoring tools, 

and the safety and effectiveness of warming devices.

248-250

Q5. Recommendation

5. No recommendation can be made regarding the safety and effectiveness of strategies to 

achieve and maintain normothermia, the lower limit of normothermia, or the optimal timing 

and duration of normothermia for the prevention of surgical site infection. (No 

recommendation/unresolved issue) (Key Question 5)

OXYGENATION

Q6. In patients with normal pulmonary function, how safe and effective is the 

perioperative use of increased fraction of inspired oxygen (FiO2) in reducing the 

risk of SSI?
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

40

To answer this question we focused on three settings of oxygen delivery: A) General anesthesia: 

Intraoperative endotracheal intubation and postoperative non-rebreathing mask, B) Neuraxial

anesthesia: Intraoperative and postoperative non-rebreathing mask and C) Postoperative only: 

Facemask and/or nasal cannula.

Q6A. General anesthesia: Intraoperative endotracheal intubation and postoperative nonrebreathing mask 

The available data examined the following comparisons:

1. 80% oxygen vs. 30% oxygen - both without nitrous oxide 

2. 80% oxygen/20% nitrous oxide vs. 35% oxygen/65% nitrous oxide - both with nitrous oxide 

started 30 minutes after surgical incision 

For all comparisons, we considered SSI the critical outcome. ASEPSIS scores, mortality, 

respiratory failure, atelectasis, tissue oxygenation, and length of stay outcomes were also 

evaluated. The evidence for this question consists of 6 RCTs.

85-90 One study89 represents a 

subanalysis of a larger study;

88 therefore results in the GRADE table reflect solely those of the 

larger study. The findings of the evidence review and the grades for all important outcomes are 

shown in Evidence Review Table 6.

Q6A.1. 80% oxygen vs. 30% oxygen - both without nitrous oxide 

Moderate-quality evidence suggested a benefit of supplemental 80% FiO2 administered via 

endotracheal intubation intraoperatively and non-rebreathing mask for 2-6 hours 

postoperatively in patients under general anesthesia. This was based on a 40% reduction in SSI 

reported in 3 studies at low risk of bias (2 in 800 elective colorectal85,87 and 1 in 210 elective 

open appendectomy86 procedures), no difference in 1 multicenter, mixed surgical 

population88,89 study at low risk of bias, and no significant difference in adverse events. 

The three studies reporting a significant SSI reduction all optimized perioperative tissue oxygen 

delivery by maintaining normothermia and avoiding hypo or hypervolemia.

85-87 Greif et al.,87

the larger colorectal study (N=500) actually confirmed optimized tissue oxygen delivery, 

measuring significantly higher intraoperative and postoperative subcutaneous tissue oxygen 

tension and higher muscle oxygen tension using 80% oxygen.

Meyhoff et al.,

88,89 the large (N=1400), multicenter, mixed population study of emergency or 

elective laparotomy for a variety of general and gynecologic surgical conditions, found no 

difference in overall, organ/space, deep, or superficial SSI. However, due to a number of 

factors, the study failed to optimize tissue oxygen delivery. While the target core temperatures 

were 36○C -37○C, the minimum reported temperatures were 35.0○C and 35.1 in each group, 

respectively. Most potentially limiting to the optimization of oxygen delivery was the 

intentional restriction of fluid replacement, limiting postoperative weight gain to less than 1kg. 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

41

Mortality at 14-30 days was rare, there was no difference between groups, and it was not 

associated with use of increased oxygenation.

85,87

 In a recent follow-up study (median 2.3 

years, range 1.3-3.4), administration of 80% oxygen was associated with significantly increased 

long-term mortality only in patients undergoing cancer surgery. The only gynecologic patients 

included in this study were those with ovarian cancer.

251 It is not clear what other cancer 

patients were included.

Q6A.2. 80% oxygen/20% nitrous oxide vs. 35% oxygen/65% nitrous oxide – both groups nitrous 

oxide started 30 minutes after incision

Moderate-quality evidence suggested no benefit of supplemental 80% FiO2 (20% nitrous oxide 

added 30 minutes after incision) administered via endotracheal intubation intraoperatively and 

non-rebreathing mask for 2-6 hours postoperatively in patients under general anesthesia. This 

was based on increased risk of SSI (all combined) in one small (N=160), mixed surgical 

population study.

90

 Several factors may account for the increased incidence of total SSIs in the 

intervention group. Patients in the 80% FiO2 group had significantly increased body mass index 

(BMI), higher blood loss, and more crystalloid infused. On multivariate logistic regression 

analysis, 80% oxygen and remaining intubated postoperatively remained predictive of SSI. 

Mortality was rare in either group and unrelated to increased supplemental oxygenation.

Q6B. Neuraxial anesthesia: Intraoperative and postoperative non-rebreathing mask

The available data on the impact of different levels of supplemental increased fraction of 

inspired oxygen on SSI in patients under regional anesthesia examined 80% oxygen versus 30% 

oxygen.

For this comparison we considered SSI the critical outcome. Length of stay outcome was also 

evaluated. The evidence for this question consists of 1 RCT.

91 The findings of the evidence 

review and the grades for all important outcomes are shown in Evidence Review Table 6.

Moderate quality evidence suggested no benefit of supplemental 80% FiO2 administered via 

non-rebreathing mask intra and postoperatively in patients under neuraxial anesthesia. This 

was based on no difference in risk of SSI in study (N=143) in cesarean sections, at low risk of 

bias.

91

 Despite no difference in blood loss between groups, it was the only factor predictive of 

SSI in an associated regression analysis. The study did not note any protocol used during the 

study to optimize tissue oxygenation. 

Q6C. Postoperative only: Facemask and/or nasal cannula

The data available on the impact of different levels of supplemental increased fraction of 

inspired oxygen used in the postoperative period only examined 28-30% oxygen versus room 

air.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

42

For this comparison we considered SSI as the critical outcome. SSI type (organ/space, superficial 

and deep SSI), ASEPSIS scores, mortality, adverse events, tissue oxygenation, and length of stay 

outcomes were also evaluated. The evidence for this question consists of 2 RCTs.

92,93

 The 

findings of the evidence review and the grades for all important outcomes are shown in 

Evidence Review Table 6.

High-quality evidence suggested no benefit of supplemental 28-30% FiO2 administered via 

facemask and/or nasal cannula solely in the postoperative period. This was based on no 

difference in SSIs from two studies.

92,93 Turtiainen et al., 92 a lower limb vascular surgery study 

(N=143) at low risk of bias used 30% oxygen via facemask in the recovery room and on the first 

postoperative day on the ward (~36 hours), followed by constant oxygen flow of 5L/min via 

nasal cannula during the second postoperative day. A significant reduction in SSI was seen only 

in isolated groin incisions. Subcutaneous tissue oxygen tension (measured hourly for the first 

four hours, then at 18 and 36 hours) was significantly higher in the supplemental oxygenation 

group. Whitney et al.,93 a second, smaller, study at high risk of bias, in 24 cervical spine 

procedures, reported no wound complications in either group with supplemental 28% oxygen 

administered at 2L/min via nasal cannula for 36 hours after discharge from the post-anesthesia 

care unit as compared to the room air group. Mortality92 and adverse events92,93 were rare, did 

not differ between groups, and were unrelated to use of supplemental oxygenation.

Q6. Recommendations

6A. For patients with normal pulmonary function undergoing general anesthesia with 

endotracheal intubation, administer increased fraction of inspired oxygen (FiO2) both 

intraoperatively and post-extubation in the immediate postoperative period. To optimize 

tissue oxygen delivery, maintain perioperative normothermia and adequate volume 

replacement. (Category IA) 85-90 (Key Question 6)

6B. No recommendation can be made regarding the safety and effectiveness of administering 

perioperative increased fraction of inspired oxygen (FiO2) for the prevention of surgical site 

infection in patients with normal pulmonary function undergoing either general anesthesia 

without endotracheal intubation or neuraxial anesthesia (i.e., spinal, epidural, or local nerve 

blocks). (No recommendation/unresolved issue) 91 (Key Question 6)

6C. No recommendation can be made regarding the safety and effectiveness of administering 

increased fraction of inspired oxygen (FiO2) via facemask or nasal cannula only during the 

postoperative period for the prevention of surgical site infection in patients with normal 

pulmonary function. (No recommendation/unresolved issue) 92,93 (Key Question 6)

Q7. What is the optimal target FiO2 to reduce the risk of SSI; how and when 

should it be administered?
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

43

Our search did not identify RCTs or SRs that both evaluated the optimal fraction of inspired 

oxygen, how and when it should be administered, and included SSI as an outcome. All studies 

evaluating the use of supplemental increased oxygenation both intraoperative and 

postoperatively used 80% FiO2 as the target level. 

Other Guidelines

Evidence-based clinical practice guidelines recommend maintaining patient homeostasis, by 

optimizing oxygenation during major surgery and in the recovery period (maintaining a >95% 

hemoglobin saturation), in concert with maintaining both patient temperature to avoid 

hypothermia and adequate perfusion during surgery.

234

Q7. Recommendation

7. No recommendation can be made regarding the optimal target level, duration, and delivery 

method of the fraction of inspired oxygen (FiO2) for the prevention of surgical site infection. 

(No recommendation/ unresolved issue) (Key Question 7)

ANTISEPTIC PROPHYLAXIS

Q8. What are the most effective strategies for preparing the patient’s skin prior 

to surgery to reduce the risk of SSI?

To answer this question we focused on four subquestions: A) How safe and effective is 

preoperative antiseptic bathing or showering? B) How safe and effective are antiseptic skin 

preparation agents individually and in combination? C) How safe and effective is the application 

of an antimicrobial sealant immediately following intraoperative skin preparation? and D) How 

safe and effective are plastic adhesive drapes? 

Q8A. How safe and effective is preoperative antiseptic bathing or showering? 

The available data examined the following comparisons:

1. Chlorhexidine gluconate (CHG) solution vs. placebo solution

2. CHG solution vs. un-medicated bar soap

3. CHG solution vs. no wash

4. CHG whole body wash vs. partial body wash

5. Aqueous iodophor solution vs. control (“routine personal hygiene”)

For all comparisons we considered SSI as the critical outcome. Product-related adverse 

reaction outcomes were also evaluated. The evidence for this question consists of 1 SR94 (7 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

44

RCTs95-101) evaluating CHG solution and 1 RCT102 evaluating povidone iodine solution. The RCTs 

span a 26 year period with 6 published between 1983 and 1992 and 2 between 2008102 and 

2009.

100

 Our search did not identify RCTs or SRs that evaluated optimal preoperative timing, 

number of showers/baths, number of product applications at each shower/bathing episode, or 

CHG-washcloths, and their impact on the risk of SSI. The findings of the evidence review and 

grades for all important outcomes are shown in Evidence Review Table 8A. 

Q8A.1. CHG solution vs. placebo solution

High-quality evidence suggested no benefit of preoperative bathing or showering with 4% CHG 

solution as compared to placebo. This was based no difference in SSI in both a meta-analysis

(N=7791) of 4 RCTs94,95,97,99,100 and a meta-analysis (N=6302) restricted to only the 2 higher 

quality studies.

94,95,99

 Each individual trial found no difference. Five months into 1 large study,

the placebo solution was found to have antimicrobial properties and was changed; however, 

the study did not stratify by or exclude that data.97 Procedures included in the studies were 

elective or potentially contaminated surgery,

95 elective inpatient surgery,97 elective clean mixed 

surgical procedures including thyroidectomy, inguinal herniorrhaphy, hip and knee surgery, 

laminectomy, mastectomy, vascular surgery,

99 and elective plastic surgery of the trunk.100

Number of preoperative showers/baths, amount of antiseptic used per bath, bathing 

instructions to each group, intraoperative antiseptic skin preparation agent, use of AMP, and 

follow up varied between studies. Three studies instructed patients to shower95,99,100 and one 

instructed them to shower or bathe.

97 Product-related adverse reactions (irritation, itching, 

reddening of the skin) were rare and did not differ between groups.

94,95,99,100

Q8A.2. CHG solution vs. un-medicated bar soap

High-quality evidence suggested no benefit of preoperative bathing or showering with 4% CHG 

solution as compared to un-medicated bar soap. This was based on no difference in SSI in a 

meta-analysis (N=1443) of 3 RCTs.

94,96-98 Heterogeneity for this comparison was high. Only the 

largest study (N=1315) reported a reduction in SSI with 4% CHG; however, no special 

showering/bathing instructions were given to the un-medicated bar soap group whereas “great 

care was taken to ensure that the patients using [CHG]...complied with the instructions.”97 For 

the two smaller, lesser quality studies, one study96 suggested a higher rate of SSI with CHG 

while the other98 suggested no difference. Number of preoperative baths, bathing instructions,

intraoperative antiseptic skin preparation agent, AMP use, procedures, and follow up varied 

between studies. One study instructed patients to bathe,

96 one to shower,98 and one to shower 

or bathe.

97

Q8A.3. CHG solution vs. no wash

Moderate-quality evidence suggested no benefit of preoperative showering with 4% CHG 

solution as compared to no wash. This was based on no difference in a meta-analysis (N=1142) 

of 3 RCTs.

94,98,100,101 Despite instructions not to shower, it is unclear if the “no wash” groups 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

45

showered. The largest study101 favored 4% CHG, while the other two98,100 suggested no 

difference. Heterogeneity for this comparison was significant. Studies included outpatient and 

inpatient procedures, patients undergoing vasectomy,

98 plastic surgery of the trunk,100 and 

elective, clean biliary tract, inguinal hernia or breast cancer101 procedures. There were also

differences in SSI definitions between studies.

Q8A.4. CHG whole body vs. partial body wash

Moderate-quality evidence suggested a benefit of a CHG shower (i.e., a whole body wash

including the scalp) as compared to a partial body wash (restricted to the proposed surgical 

site). This was based on reduced risk of SSI with whole body washing (1 time, 2 applications on 

the afternoon before surgery) in one large RCT (N=1093) of elective clean biliary tract, inguinal 

hernia, and breast cancer procedures.

94,101

Q8A.5. Aqueous iodophor solution vs. control (“routine personal hygiene”)

Very low-quality evidence suggested no benefit of preoperative shower with 10% aqueous 

iodophor solution as compared to routine personal hygiene. This was based on no infections 

reported in either group in 1 small RCT (N=114) in elective, clean plastic surgical procedures 

(thorax or abdomen) designed to evaluate the product’s efficacy in reducing skin 

contamination, not SSI.

102

Other Guidelines

Clinical practice guidelines recommend that patients shower or bathe with an antiseptic agent 

or soap on at least the night before surgery.

12,234

 They do not favor the use of one antiseptic 

agent in preference of another. There may be contraindications for specific antiseptic-agent 

use in some patients or surgical procedures. 

Q8B. How safe and effective are antiseptic skin preparation agents individually 

and in combination?

The available data examined the following comparisons:

1. Aqueous iodophor: 1-step vs. 2-step

2. Aqueous iodophor (1 or 2-step) vs. iodophor in alcohol (1-step with or without adhesive 

drape)

3. CHG-alcohol (1 or 2-step) vs. aqueous iodophor (1 or 2-step)

4. CHG-alcohol (1 or 2-step) vs. iodophor-alcohol (1 or 2-step)

a. CHG-alcohol (2-step) vs. iodophor-alcohol (2-step)

b. CHG-alcohol (1-step) vs. iodophor-alcohol (1-step)

For all comparisons, we considered SSI the critical outcome. Product-related adverse event

outcomes were also evaluated. The evidence for this question consists of 14 RCTs.

103-116 The 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

46

findings of the evidence review and the grades for all important outcomes are shown in 

Evidence Review Table 8B.

Q8B.1. Aqueous iodophor: 1-step vs. 2-step 

High-quality evidence suggested no benefit of using 2-step as compared to 1-step aqueous 

iodophor for skin preparation of the surgical site. This was based on no difference in SSI in 2 

RCTs at moderate risk of bias.

103,104 One study in 234 clean (30%) and clean-contaminated (70%) 

oncologic, non-laparoscopic abdominal procedures compared povidone iodine paint (1% 

iodine) to a 5 minute povidone iodine scrub (0.75% iodine) followed by povidone iodine paint 

(1% iodine).103 Another study in 108 CABG procedures did not report the product 

concentration or scrub duration.104 In the latter study, patients were also instructed to take 

antimicrobial showers (unspecified product) the evening before and the morning of surgery.

Q8B.2. Aqueous iodophor (1 or 2-step) vs. iodophor in alcohol (1-step with or without adhesive 

drape)

Moderate-quality evidence suggested no benefit of iodophor in alcohol as compared to 

aqueous iodophor. This was based on no difference in SSI in a meta-analysis (N=626) of 5 RCTs

including 4 RCTs at moderate risk104-107 and 1 at low risk108 of bias. Only one study at moderate

risk of bias in CABG procedures showed a reduced risk of sternal SSI with iodophor in alcohol 

(with or without plastic adhesive drape).

104 A second study (low risk of bias) in CABG 

procedures using iodophor impregnated plastic adhesive drape at the sternal site showed no 

difference between groups.

108 The three remaining studies (moderate risk of bias) in THA and 

TKA,

106 shoulder,107 and foot and ankle105 procedures reported no infections, however, each 

was designed to evaluate the products’ efficacy in reducing skin contamination, not SSI.

Q8B.3. CHG-alcohol (1 or 2-step) vs. aqueous iodophor (1 or 2-step) 

High-quality evidence suggested a benefit of CHG-alcohol as compared to aqueous iodophor. 

This was based on a reduced risk of SSI in a meta-analysis (N=1976) of 5 RCTs (two low 

risk,

109,110 one moderate risk,107 and two high risk111,112 of bias) and no difference in productrelated adverse events. Only one large study showed a reduced risk of SSI in multiple mixed 

clean-contaminated abdominal and non-abdominal (thoracic, gynecologic, and urologic) 

procedures.110 CHG-alcohol was specifically associated with reduced risk of superficial and 

deep incisional SSI, but not organ space SSI or sepsis. The study in clean hernia repairs 

(herniotomy, herniorraphy, or hernioplasty) showed no difference between groups.

109 In both 

of these studies, authors reported receiving funds from and/or being employed by the 

manufacturer of the CHG-alcohol product. Of the three studies at moderate or high risk of bias, 

one in clean, clean-contaminated or contaminated general surgery112 procedures showed no 

difference, and the studies in clean elective shoulder107 and foot and ankle111 procedures 

reported no infections; however, each was designed to evaluate the products’ efficacy in 

reducing skin contamination, not SSI.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

47

High-quality evidence from 2 studies suggested no difference in product-related adverse events 

including skin irritation or pruritis or erythema around the wound.

110,112

Q8B.4. CHG-alcohol (1 or 2-step) vs. iodophor-alcohol (1 or 2-step) 

High-quality evidence suggested no benefit of CHG-alcohol (1 or 2-step) as compared to 

iodophor alcohol (1-or 2 step). This was based on no difference in SSI in a meta-analysis 

(N=1223) of 5 RCTs.

107,113-116

 Three studies (one low risk,

115 one moderate risk,113 and one high 

risk114 of bias) compared 2-step application, and two studies107,116 (moderate risk of bias) 

compared 1 step product application. There was no difference in SSI in individual metaanalyses of “2-step” or “1-step” product application. Details are available under the individual 

comparators below.

Q8B.4.a. CHG-alcohol (2-step) vs. iodophor-alcohol (2-step)

High-quality evidence suggested no benefit of 2-step CHG-alcohol as compared to 2-step 

iodophor-alcohol. This was based on no difference in SSI in 3 studies comparing 0.5% 

chlorhexidine gluconate and alcohol with 10% povidone-iodine (1% available iodine) and 23% 

isopropyl alcohol.113-115 No preoperative antiseptic shower protocol was reported in the studies. 

The large, moderate risk of bias study in a mixed general surgery population reported no 

difference.115 CHG-alcohol was associated with a significant reduction in SSI in biliary and “other 

clean procedures”. One study (high risk of bias) in elective, clean, plastic surgery breast 

procedures reported no difference between groups.114 The smallest study (moderate risk of 

bias) in foot procedures reported no infections in either group.113 However, the study was 

designed to evaluate the products’ efficacy in reducing skin contamination, not SSI.

Q8B.4.b. CHG-alcohol (1-step) vs. iodophor-alcohol (1-step)

High-quality evidence suggested no benefit of 1-step CHG-alcohol as compared to 1 step 

iodophor-alcohol. This was based on no difference in SSI in two studies at moderate risk of bias 

comparing 2% chlorhexidine gluconate with 70% alcohol (water insoluble film) to 0.7% iodine 

with 74% alcohol (water insoluble film).107,116 One study in shoulder procedures (96 

arthroscopies and 4 arthroplasties) reported no infections in either group.

107 Patients were 

instructed to shower the evening prior to surgery (product not reported). Iodophorimpregnated plastic adhesive drapes were applied to the shoulder arthroplasties’ operative 

site. The second study reported only one wound infection following 80 foot and ankle 

procedures.

116 Patients were not instructed to take an antiseptic shower prior to surgery. Both 

studies were designed to evaluate the products’ efficacy in reducing skin contamination, not 

SSI, and both received funding by one or both product manufacturers.

Other Guidelines
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

48

Clinical practice guidelines recommend skin preparation with an antiseptic agent, but do not 

favor one antiseptic agent over another.

12,234 There may be contraindications to use of specific 

antiseptic skin preparation agents.

Q8C. How safe and effective is the application of an antimicrobial sealant

immediately following intraoperative skin preparation?

The available data examined the application of a cyanoacrylate-based anti-microbial skin 

sealant immediately after skin preparation as compared to no sealant.

For this comparison we considered SSI as the critical outcome. Product-related adverse event

outcomes were also evaluated. The evidence for this question consists of 3 RCTs.

117-119 The 

findings of the evidence review and the grades for all important outcomes are shown in 

Evidence Review Table 8C. 

High-quality evidence suggested no benefit of cyanoacrylate-based antimicrobial skin sealant

applied immediately following skin preparation. This was based on no difference in SSI in a 

meta-analysis (N=553) of 3 RCTs evaluating surgical site skin preparation with povidone iodinealcohol117,118 or aqueous povidone iodine 118,119 solution followed by application of 

cyanoacrylate-based skin sealant before skin incision (1 CABG sternal and/or venous harvest 

site,

118 1 CABG leg saphenous vein harvest site,117 1 open inguinal hernia repair119). The two 

CABG studies also followed skin sealant application with plastic adhesive drape application. 

Two studies at low risk of bias suggested no difference between groups.118,119 However, due to 

the low number of events in the latter study, superiority of the antimicrobial sealant could not 

be established and study enrollment ceased once the cyanoacrylate sealant was granted 

regulatory approval by the FDA (based on porcine data on skin contamination.

119 Both studies 

were funded by and/or authors had a financial relationship with the skin sealant manufacturer. 

Only one small study117 (low risk of bias) suggested a reduced risk of SSI; however, authors 

acknowledged that the apparent increased risk of SSI in the control legs could be explained by 

their use of a grading system252 whose stringent criteria included minimal erythema or 

discharge as SSI. High-quality evidence suggested no significant product-related sensitivity or 

other adverse events.

117-119 In the inguinal hernia repair study surgeons reported difficulty 

incising through the clear film (4/166 patients) and one reported visible “flaking” of the film at 

the time of procedure (no report of plastic adhesive drape use).

119

Q8D. How safe and effective are plastic adhesive drapes? 

The available data examined the following comparisons:

1. Non-iodophor impregnated adhesive drape vs. no drape

2. Iodophor-impregnated adhesive drape vs. no drape
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

49

For all comparisons, we considered SSI as the critical outcome. The evidence for this question 

consists of 6 RCTs.

104,120-124 The findings of the evidence review and the grades for all important 

outcomes are shown in Evidence Review Table 8D.

Q8D.1. Non-iodophor impregnated drape vs. no drape

High-quality evidence suggested no benefit of non-iodophor impregnated plastic adhesive 

drapes in addition to skin preparation as compared to skin preparation alone. This was based 

on no difference in SSI in a meta-analysis (N=1742) of 4 RCTs spanning a 30 year period (1971-

2001), each reporting no difference.

120-123 The two most recent studies120,121 used polyurethane 

adhesive drapes; drape material information was not reported in the older122,123 studies. The 

surgical skin preparation agent applied prior to the application of the adhesive drapes varied 

between studies and may have impacted drape adhesion. Studies included general 

surgery,

122,123 cesarean section,120 and hip fracture121 surgery.

Q8D.2. Iodophor-impregnated drape vs. no drape 

High-quality evidence suggested no benefit of iodophor-impregnated plastic adhesive drapes in 

addition to skin preparation as compared to skin preparation alone. This was based on no 

difference in SSI in a meta-analysis (N=1113) of 2 RCTs, spanning a 15 year period (1987-2002) 

each reporting no difference.

104,124 Both studies used povidone iodine –alcohol skin preparation 

(2-step application in the study at low risk of bias in abdominal procedures124 and one-step 

application in the study at moderate risk of bias in CABG104 procedures).

Other guidelines

One evidence-based clinical practice guideline recommends against the routine use of noniodophor impregnated plastic adhesive drapes and recommends that if a plastic adhesive drape 

is required, then an iodophor-impregnated one should be used (unless the patient has an 

iodine allergy).

234

Q8. Recommendations

8A. Advise patients to shower or bathe (full body) with either soap (antimicrobial or nonantimicrobial) or an antiseptic agent on at least the night before the operative day (Category 

IB) 94-102 (Key Question 8A)

8A.1. No recommendation can be made regarding the optimal timing of the preoperative 

shower or bath, the total number of soap or antiseptic agent applications, or the use of 

chlorhexidine gluconate washcloths for the prevention of surgical site infection. (No 

recommendation/ unresolved issue) (Key Question 8A)

8B. Perform intraoperative skin preparation with an alcohol-based antiseptic agent, unless 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

50

contraindicated. (Category IA) 103-116 (Key Question 8B)

8C. Application of an antimicrobial sealant immediately following intraoperative skin 

preparation is not necessary for the prevention of surgical site infection. (Category IA) 117-119

(Key Question 8C)

8D. Use of plastic adhesive drapes with or without antimicrobial properties, is not necessary for 

the prevention of surgical site infection. (Category II) 104,120-124 (Key Question 8D)

Q9. How safe and effective is antiseptic irrigation prior to closing the surgical 

incision?

Our search did not identify RCTs or SRs that evaluated the safety and effectiveness of soaking

surgical implants (e.g., meshes, neurosurgical ventricular shunts) in antiseptic solution prior to 

insertion (in combination with parenteral AMP) and its impact on SSI. 

The available data examined aqueous iodophor irrigation versus normal saline for the

prevention of surgical site infection.

For this comparison, we considered superficial and deep SSIs and organ/space abscess as the 

critical outcomes. Product related adverse events including wound healing and iodine toxicity 

outcomes were also evaluated. The evidence for this question consists of 7 RCTs.125-131 In all 

studies, both groups received parenteral AMP, but the specific protocol was not necessarily 

described in all. The findings of the evidence review and the grades for all important outcomes 

are shown in Evidence Review Table 9.

Moderate-quality evidence suggested a benefit of intraoperative aqueous iodophor irrigation of 

the deep incision, in combination with parenteral AMP, for clean spine procedures. This was 

based on moderate-quality evidence from a meta-analysis (N=660) of 2 RCTs suggesting a 

reduced risk of deep SSI when the deep tissues were irrigated and allowed to soak for 3 

minutes with 0.35% povidone iodine solution, then irrigated with an additional 2L of normal

saline prior to bone grafting and spinal instrumentation.125,126 All procedures in both studies 

were performed by the same surgeon. Perioperative AMP included preoperative parenteral 

dose, postoperative parenteral dosing for 2 days followed by oral prophylaxis for an additional 

3 days. Over 80% of the SSIs were MRSA SSIs.

High-quality evidence suggested a benefit of aqueous iodophor irrigation of the subcutaneous 

tissue, in combination with parenteral AMP, for clean-contaminated, contaminated, and dirty 

open abdominal procedures. This was based on reduced risk of superficial SSI on meta-analysis 

(N=329) of 2 RCTS that performed 60 seconds of subcutaneous tissue irrigation with 10% 

aqueous iodophor solution prior to wound closure.127,128 The larger 127study administered 

parenteral AMP preoperatively and for 48 hours postoperatively, while the smaller128 study 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

51

only reports administering perioperative parenteral AMP. Individual meta-analyses of cleancontaminated (N=149) and dirty (N=90) procedures both showed reduced risk of superficial SSI.

Moderate-quality evidence suggested no benefit of aqueous iodophor peritoneal lavage in 

contaminated and dirty general surgical abdominal cases. This was based on no difference in 

organ/space abscess formation in meta-analysis (N=268) of 3 RCTs.129-131 Aqueous iodophor 

solution amount, concentration, application, and perioperative AMP regimen varied between 

studies.

High-quality evidence from 3 studies suggested no increased risk of product-related adverse 

events

126,128,129 or iodine toxicity.128,129,131

 Moderate-quality evidence from 2 studies suggested 

no wound healing problems.125,128

Q9. Recommendation

9A. Consider intraoperative irrigation of deep or subcutaneous tissues with aqueous iodophor 

solution for the prevention of surgical site infection. Intra-peritoneal lavage with aqueous 

iodophor solution in contaminated or dirty abdominal procedures is not necessary. (Category 

II) 125-131 (Key Question 9)

9B. No recommendation can be made regarding the safety and effectiveness of soaking 

prosthetic devices in antiseptic solutions prior to implantation for the prevention of surgical site 

infection. (No recommendation/ unresolved issue) (Key Question 9)

Q10. How safe and effective is repeat application of an antiseptic skin 

preparation agent to the surgical site immediately prior to closing the surgical 

incision?

The available data examined the repeat application of aqueous iodophor solution to the 

patient’s skin immediately prior to closing the surgical incision versus no additional application 

of topical antiseptic agent for the prevention of surgical site infection. Our search did not 

identify RCTs or SRs that evaluated repeat application of chlorhexidine, chlorhexidine-alcohol, 

iodophor alcohol or other topical antiseptic agent The findings of the evidence review and the 

grades for all important outcomes are shown in Evidence Review Table 10.

Low-quality evidence suggested no benefit of application of aqueous iodophor solution to the 

patient’s skin immediately prior to closing the surgical incision, in combination with parenteral 

AMP. This was based on no difference in SSI (combined or individual incisional or organ/space 

SSI) in a small study at high risk of bias, in 107 gastric and colorectal procedures.132
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

52

Q10. Recommendation

10. No recommendation can be made regarding the safety and effectiveness of repeat 

application of antiseptic agents to the patient’s skin immediately prior to closing the surgical 

incision for the prevention of surgical site infection. (No recommendation/unresolved issue)

132

(Key question 10)
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

53

VII. Evidence Review- Prosthetic Joint Arthroplasty section

BLOOD TRANSFUSION

Q11. How do perioperative blood transfusions impact the risk of SSI in 

prosthetic joint arthroplasty patients? 

To answer this question we first addressed the general question of any blood transfusion and 

its impact on the risk of SSI. We then focused on four subquestions: A) Are specific blood 

products associated with a risk of SSI? B) If the risk of SSI in increased, can this effect be isolated 

from the risk associated with more complex cases? C) How does the volume of transfused 

blood product impact the risk of SSI? and D) How safe and effective is withholding blood 

transfusion to reduce the risk of SSI?

For the general question of risk of any blood transfusion on SSI, we considered SSI as the critical 

outcome. The evidence for this question consists of 2 RCTs133,134 and 4 OBS135-138 studies. All of 

the studies reflect European transfusion practices between 1999 and 2007. Studies were 

published between 2001 and 2008; however, only 2 report the study periods (1998-2000).

137,138

 

All studies were at low risk of bias. When reported, hemoglobin thresholds for blood 

transfusion ranged between 8 and 11g/dL. The findings of the evidence review and the grades 

for all important outcomes are shown in Evidence Review Table 11.

High-quality evidence suggested blood transfusions increased the risk of SSI. This was based on 

increased risk of SSI in a meta-analysis (N=8493) of 6 studies, 2 RCTs133,134 and 4 OBS studies,

135-

138 and a separate meta-analysis (N=7484) of the 4 OBS studies. Analysis combined allogeneic, 

autologous, and autologous plus allogeneic blood transfusion data. Data in both of these 

meta-analyses may be driven by 2 OBS studies with a large number of patients who received 

allogeneic only blood transfusion and the possibility of selection bias inherent in observational 

studies.136,138 In contrast, meta-analysis (N=1009) of the 2 RCTs (N=1009) does not suggest an 

increased risk of SSI with autologous and autologous plus additional allogeneic blood 

transfusions.

Q11A. Are specific blood products associated with a risk of SSI? 

The available data examined the following comparisons:

1. Allogeneic blood (any) vs. no transfusion

a. Allogeneic not WBC depleted vs. no transfusion

b. Allogeneic WBC depleted vs. no transfusion

c. Allogeneic “buffy coat depleted” vs. no Transfusion

d. Allogeneic WBC filtered vs. no transfusion

e. Allogeneic “lower WBC content” vs. allogeneic “higher WBC content”

2. Autologous blood (any) vs. no transfusion

a. Autologous ±WBC filtration vs. no transfusion 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

54

b. Autologous whole blood vs. no transfusion

c. Autologous “not WBC depleted” vs. no transfusion

d. Autologous buffy coat depleted vs. no transfusion

e. Autologous “lower WBC content” vs. autologous “higher WBC content”

f. Post-operative salvage only vs. autologous donated blood 

3. Allogeneic blood (any) vs. autologous blood (any)

a. Allogeneic WBC± WBC depleted vs. autologous not WBC depleted

b. Allogeneic WBC filtered vs. autologous buffy coat depleted.

4. Combined autologous and allogeneic (any) vs. no transfusion

a. Combined autologous and allogeneic vs. autologous only

For all comparisons, we considered SSI, PJI, or reoperation due to wound infection as the

critical outcomes. Wound disturbance outcome was also evaluated. The evidence for this 

question consists of 2 RCTs133,134 and 7 OBS135-141 studies. There were differences between 

studies including: surgical procedures, definition of SSI, blood product WBC content, length of 

blood product storage, hemoglobin transfusion trigger levels and other criteria for transfusion, 

as well as follow up. In several studies, missing data resulted in discrepancies in the numbers. 

The findings of the evidence review and the grades for all important outcomes are shown in 

Evidence Review and GRADE Table 11A.

1. Allogeneic blood transfusions

Q11A.1. Allogeneic blood (any) vs. no transfusion

Low-quality evidence suggested that allogeneic blood transfusions increased the risk of SSI. 

This was based on increased risk of SSI in a meta-analysis (N=5737) of 4 OBS135-138 studies in 

primary and revision THA and TKA and no difference in reoperation due to wound infection in 

another OBS139 study. See individual comparators in GRADE table 9A for specific study findings. 

2. Autologous blood transfusions

Q11A.2 Autologous blood (any) vs. no transfusion 

Moderate-quality evidence suggested that autologous blood transfusions did not increase the 

risk of SSI. This was based on no difference in a meta-analysis (N=970) of 2 RCTs.

133,134 One 

large RCT in THA suggested no difference at 90 days of follow up.

133 The second small RCT in 

THA reported no infections in either group; however, this study was designed to evaluate 

transfusion induced immunomodulation, not SSI, and follow up was limited to 7 days.

134 In 

contrast, 1 large136 (N=912) prospective OBS study in primary and revision THA and TKA 

suggested reduced risk of SSI and a smaller135 study in primary THA and TKA reported only 1 

infection in the transfused group. See individual comparators in GRADE table 11A for specific

study findings.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

55

3. Allogeneic vs. Autologous blood transfusions

Q11A.3. Allogeneic blood (any) vs. autologous blood (any)

Moderate-quality evidence suggested that allogeneic blood transfusions increased the risk of 

SSI. This was based on a greater than 4 fold increase in risk in a meta-analysis (N=2592) of 3 

OBS studies.

135,136,140 Allogeneic blood products included whole blood, WBC depleted, WBC 

filtered and not filtered; autologous included whole blood, buffy coat depleted, and 

perioperative cell salvage-washed blood. See individual comparators in GRADE table 11A for 

specific study findings.

4. Combined Autologous and Allogeneic blood transfusions

Q11A.4. Combined autologous and allogeneic blood (any) vs. no transfusion 

Moderate-quality evidence suggested that combined autologous and additional allogeneic 

blood transfusions did not increase the risk of SSI. This was based on no difference in 

subanalysis in 1 RCT133 (N=470) and 2 OBS135,136 studies (N=1632). In each study, patients 

received allogeneic blood transfusion only after all (2-3 units) of the autologous donated blood 

(with or without additional salvage blood) had been transfused. Autologous blood products 

included autologous blood donation whole blood, packed red blood cells, salvage blood,

136

“buffy coat depleted”,

135 or “WBC filtered”133. Allogeneic blood products included “WBC 

depleted or not depleted”,

136 or “WBC filtered (WBCF)”.135,138 Transfusion triggers included: 

hemoglobin levels of 8-9g/dL,

133,136 <11g/dL for autologous transfusions and <6g/dL for 

allogeneic transfusions or <10g/dL in patients with cardiovascular or cerebrovascular disease, 

or symptomatic anemia in another141 study. See individual comparators in GRADE table 11A for 

specific study findings.

Other Guidelines

Recent blood transfusion practice guidelines recommend more restrictive transfusion strategies

than those used in these studies.

253 In hemodynamically stable postoperative surgical patients, 

transfusion is recommended for hemoglobin levels of 8g/dL or less for symptoms (e.g., chest 

pain, orthostatic hypotension or tachycardia unresponsive to fluid resuscitation, or congestive 

heart failure). In adult and pediatric intensive care unit patients, the recommended 

hemoglobin level for transfusion is 7g/dL or less. 

Q11B. If the risk of SSI is increased, can this effect be isolated from the risk 

associated with more complex cases? 

Our search did not identify data that directly evaluated the association between increasing 

blood transfusion requirements, more complex cases, and the risk of SSI in prosthetic joint 

arthroplasty patients. However, data from 3 OBS136,138,141 studies stratified blood transfusion 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

56

requirements and 1 OBS136 study reported blood loss, both by procedure type. See individual

comparators in GRADE table 11B for specific study findings.

Q11C. How does the volume of transfused blood product impact the risk of SSI?

Our search did not identify data that evaluated differences in the volume of transfused blood 

product and their impact on the risk of SSI in prosthetic joint arthroplasty patients.

Q11D. How safe and effective is withholding blood transfusions to reduce the 

risk of SSI?

Our search did not identify data that both evaluated the safety and effectiveness of withholding 

blood transfusions and its impact on the risk of SSI in prosthetic joint arthroplasty patients. 

Other Guidelines

Clinical practice guidelines recommend against withholding transfusion of necessary blood 

products from surgical patients as a means to prevent SSI.

12

Q11. Recommendation

11A. No recommendation can be made regarding the perioperative management of blood 

transfusions for the prevention of surgical site infection in prosthetic joint arthroplasty. (No 

recommendation/unresolved issue)133-141 (Key Question 11A-C)

11B. Do not withhold transfusion of necessary blood products from surgical patients as a means 

to prevent surgical site infection. (Category IB) 12 (Key Question 11D)

SYSTEMIC IMMUNOSUPPRESSIVE THERAPY

Q12. How does systemic corticosteroid or other immunosuppressive therapy 

impact the risk of SSI in prosthetic joint arthroplasty patients? 

Immunosuppressive therapy agents used to treat rheumatoid arthritis (RA) are divided into 

disease modifying antirheumatic drugs (DMARDs) and biologic agents. The most common 

DMARD is methotrexate, but can also include hydroxychloriquine, leflunomide, minocycline, 

sulfasazaline, azathioprine, cyclosporine and gold. DMARD combination therapy includes 2 or 3 

drugs, most of which are methotrexate based. Biologic agents are commonly divided into “nontumor necrosis factor (TNF)” agents (e.g., anakinra, abatacept, rituximab, and tocilizumab) and 

“anti-TNF” agents (e.g., adalimumab, etanercept, infliximab, certolizumab pegol, and 

golimumab). In the treatment of both early (<6 months) and established (>6 months) RA, 

progression from DMARD monotherapy, to DMARD double or triple therapy, to use of biologic 

agents is indicative of progression from low to high disease activity with or without poor 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

57

prognostic features (e.g., functional limitation, extra-articular disease, positive rheumatoid 

factor or anti-cyclic citrullinated peptide antibodies, and bony erosion by radiographs).254 

Systemic corticosteroids most commonly refer to oral prednisone use. 

To answer this question, we focused on two subquestions: A) Does the type of agent impact the 

risk of SSI? B) Does the preoperative duration of therapy impact the risk of SSI? and C) Does the 

agent dose impact the risk of SSI?

Q12A. Does the type of agent impact the risk of SSI?

The available data examined the following comparisons:

1. Biologic agents (non-TNF and anti-TNF) vs. disease modifying antirheumatic drugs (DMARDs)

2. DMARDs: methotrexate vs. no DMARD therapy

For all comparisons we considered SSI, PJI, superficial SSI, deep wound abscess, and infected 

hematoma as the critical outcomes. Drug-related adverse events, as well as adverse events of 

the surgical wound necrotic eschar, and serous drainage outcomes were also evaluated. 

“Adverse events of surgical wound” was a composite variable that included: wound dehiscence 

(not completely healed 14 days after surgery or needs secondary closure), continued discharge,

and culture-positive infection. The evidence for this question consists of 4 OBS studies in RA 

patients.

142-145 All studies were at low risk of bias. The findings of the evidence review and the 

grades for all important outcomes are shown in Evidence Review Table 12A.

Q12.1. Biologic agents (non-TNF and anti-TNF) vs. DMARDs

Very low-quality evidence suggested biologic agent therapy (non-TNF and anti-TNF) increased 

the risk of SSI. This was based on greater than 5-fold increase in risk of SSI and superficial SSI, 

but no difference in PJI in 3 separate meta-analyses (N=528) of 2 OBS studies.

142,143

 

Multivariate logistic regression analyses in both studies identified biologic agents as a 

significant risk factor for infection, and in one study142 they were also a risk factor for deep 

venous thrombosis (DVT). Very-low quality evidence also suggested no difference in other 

adverse events of the surgical wound.

144

 For superficial SSI, the large143 study in primary or 

revision THA or TKA RA patients (superficial SSI rate 18.8%) reported a significantly increased 

risk with biologic agents while the smaller142 study (superficial SSI rate of 7.4%) reported no 

difference. The large and small studies each reported no difference in PJI, however the number 

of events in both groups (n=3 and 1, respectively) and the number of patients in the smaller 

one (N=108) limited the power of the analyses.

Biologic agents included anti-TNFs (etanercept, infliximab, adalimumab) and non-TNFs 

(anakinra, abatacept and rituximab). In each study patients had established RA (on average > 

10 years). All patients on biologic agent therapy also received prednisone 3-5mg/day, and the 

majority also received methotrexate (88%142 to 92%144) and/or another DMARD142 (13%). 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

58

DMARD patients in all three studies were on single or multiple DMARD therapy in addition to 

daily prednisone (average, 3mg/day). The most common DMARD was methotrexate but none 

of the studies reported average weekly doses and only one reported the DMARD perioperative 

administration protocol (it was administered continuously).143

Q12.2. DMARDs: methotrexate vs. no DMARD therapy

Very low-quality evidence suggested methotrexate therapy did not increase the risk of SSI. 

This was based on no difference in PJI, deep wound abscess, infected hematoma, necrotic 

eschar, or serous drainage at 6 months of follow up in 1 OBS study.

145 Both the study size and 

the total number of events for each outcome were limited. This 1991 study utilized data 

collected between 1978 and 1987 with patients on a mean weekly methotrexate dose of 8.7mg 

(range: 7.5-12.5mg) and could be considered sub-therapeutic in current clinical practice.

255 The 

methotrexate group included both patients who had continued and patients who had stopped 

methotrexate within 4 weeks of surgery. While patients in the no therapy group had never 

taken methotrexate, some were on daily prednisone (study does not report how many). 

Q12B. Does the preoperative duration of the therapy impact the risk of SSI?

Our search did not identify data that directly evaluated length of time that immunosuppressive 

therapy was used preoperatively and its impact on the risk of SSI in prosthetic joint arthroplasty 

patients. Thus, we evaluated disease duration as a proxy. We considered SSI as the critical 

outcome. The evidence for this question consists of 2 OBS studies.

142,143 Our search did not 

reveal data that evaluated patients with early RA (<6 months). The findings of the evidence 

review and the grades for all important outcomes are shown in Evidence Review Table 12B.

Low-quality evidence suggested that in patients with established RA (>6 months), years of 

disease duration was a risk factor for SSI. This was based on increased risk in 2 OBS studies that 

performed multivariate logistic regression analyses comparing infected to non-infected patients 

on biologic (anti-TNF) agents and DMARDs.

142,143

Q12C. Does the agent dose impact the risk of SSI? 

Our search did not identify data that directly evaluated different doses of biologic agents or

DMARDs and their impact on the risk of SSI in arthroplasty patients. The available data 

examined doses of prednisone and risk of SSI in patients on biologic agents (anti-TNF) as 

compared to those on DMARDs.

For this comparison, we considered SSI as the critical outcome. The evidence for this question 

consists of 2 OBS studies in RA patients.142,143 The findings of the evidence review and the 

grades for all important outcomes are shown in Evidence Review Table 12C.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

59

Very low-quality evidence suggested higher prednisone dose increased the risk of SSI. This was 

based on increased risk of SSI on multivariate logistic regression analyses comparing infected 

and non-infected patients in 2 OBS studies.

142,143 The small study, with the majority of patients 

on combination biologic/DMARD or dual DMARD therapy, suggested that increasing prednisone 

dose was a risk factor for SSI.

142 Patients in the biologic agent group were on significantly higher 

daily prednisone doses (5mg/day; range 2-7) than those in the DMARD group (3mg/day; range 

0-5). The larger study, where none of the patients were on combination biologic and DMARD 

therapy, suggested prednisone dose was not a risk factor for SSI. Patient in both groups were 

on an average prednisone dose of 3mg/day (range, 0-5).

143 Results were not stratified by 

immunosuppressive therapy agent.

Q13. What are the most effective strategies in managing systemic 

corticosteroids or other immunosuppressive therapy perioperatively to reduce 

the risk of SSI in prosthetic joint arthroplasty patients?

To answer this question we focused on two subquestions: A) How safe and effective is the 

discontinuation of these agents preoperatively and when should they be resumed? and B) 

Should the agent dose be adjusted, and if so, for how long?

Q13A. How safe and effective is the discontinuation of these agents 

preoperatively and when should they be resumed?

The available data examined the following comparisons:

1. DMARDs: methotrexate stopped vs. continued perioperatively

2. Biologic agents: anti-TNF stopped vs. continued perioperatively

The evidence for this question consists of 4 OBS studies examining DMARDs145-148 and 1 OBS

study examining biologic agents148 in RA patients. All studies were at low risk of bias. For all 

comparisons we considered PJI the critical outcome. RA flares, infected hematomas, necrotic 

eschar, and non-communicating serous drainage outcomes were also evaluated. The findings of 

the evidence review and the grades for all important outcomes are shown in Evidence Review 

Table 13A.

Q13A.1. DMARDs: methotrexate stopped vs. continued perioperatively

Low-quality evidence suggested no increased risk of PJI with methotrexate continued 

throughout the perioperative period. This was based on no difference in PJI in a meta-analysis 

of 3 small145-147 OBS studies and a separate 148 OBS study. In the meta-analysis, both the 

number of patients (N=135) and events (n=6) were small. The studies were performed 

between 1991 and 1996 and the methotrexate doses could be considered subtherapeutic in 

current practice.

255 Procedures followed and length of time during which therapy was stopped
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

60

varied. In a larger study, stopping DMARD therapy at the time of surgery (not defined) reduced 

the incidence of subsequent PJI.148

Q13A.2. Biologic agents: anti-TNF stopped vs. continued perioperatively

Very low-quality evidence suggested no difference in risk of PJI with continuation of biologic 

(anti-TNF) therapy perioperatively. This was based on no difference in risk of PJI in a small 

subanalysis in 1 OBS study in THA and TKA patients.

148 Both the number of patients (N=50) and 

events (n=3), all in the group continuing biologic agent therapy perioperatively, were very 

small. 

Q13B. Should the agent dose be adjusted, and if so, for how long? 

Our search did not identify data that evaluated perioperative immunosuppressive therapy dose 

adjustment and its impact on the risk of SSI in prosthetic joint arthroplasty patients.

Other Guidelines

Clinical practice guidelines provide conflicting recommendations regarding the perioperative 

management of immunosuppressive therapy. In 2008 the American College of Rheumatology 

provided no recommendation for the perioperative management of DMARDs due to the 

“absence of consistent evidence”.

256 The following year, a multinational guideline suggested 

that methotrexate could be safely continued in the perioperative period in RA patients 

undergoing elective orthopaedic surgery.

255 Their recommendation was based on studies with 

low methotrexate dosing (4-13mg/week). For biologic agents, the British Society for 

Rheumatology recommended in 2005 that treatment with anti-TNF agents be withheld for 2-4 

weeks prior to major surgical procedures and restarted postoperatively if there was no 

evidence of infection and wound healing was satisfactory.

257

Recommendations were based 

solely on information provided by pharmaceutical companies. In 2008, the American College 

of Rheumatology (ACR) recommended that biologic agents not be used for at least one week 

prior to and one week following surgery (based on the pharmacokinetic properties of a given 

agent).

256 The 2012 ACR update does not address perioperative management of 

immunosuppressive therapy.

254

Q12 and Q13. Recommendation

12 and 13. No recommendation can be made regarding the perioperative management of 

systemic corticosteroid or other immunosuppressive therapy for the prevention of surgical site 

infection in prosthetic joint arthroplasty. (No recommendation/ unresolved issue) 142-148 (Key 

Questions 12 and 13)
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

61

Q14. What is the optimal duration of postoperative AMP to reduce the risk of 

SSI in prosthetic joint arthroplasty patients who are on systemic corticosteroid 

or other immunosuppressive therapy?

Our search did not identify data that specifically evaluated differences in duration of 

postoperative AMP in prosthetic joint arthroplasty patients who were on systemic 

corticosteroids or other immunosuppressive agents and its impact on the risk of SSI. However, 

multiple procedures examined in the Core section, Q1.E: Postoperative AMP duration that 

included patients on immunosuppressive therapy showed no benefit of continuing AMP after 

closing the surgical incision in the operating room. Therefore, the broader recommendation for 

duration of postoperative AMP should be applied to prosthetic joint arthroplasty procedures 

irrespective of use if systemic corticosteroid or other immunosuppressive therapy.

Q14. Recommendation

14. For prosthetic joint arthroplasty patients on systemic corticosteroid or other 

immunosuppressive therapy, Recommendation 1E applies: In clean and clean-contaminated 

procedures, do not administer additional prophylactic antimicrobial agent doses after the 

surgical incision is closed in the operating room, even in the presence of a drain. (Category 

IA)27-65 (Key question 14)

INTRA-ARTICULAR CORTICOSTEROID INJECTIONS

Q15. How do preoperative intra-articular corticosteroid injections impact the 

risk of SSI in prosthetic joint arthroplasty patients?

The available data examined the following comparisons:

1. History of corticosteroid injection vs. no injection

a. TKA: Injection vs. no injection

b. THA: Injection vs. no injection

For all comparisons we considered any SSI, PJI, and superficial SSI as the critical outcomes. The 

evidence for this question consists of 2 OBS studies in TKA149,150 and 3 OBS studies in THA151-153

patients. All studies were at low risk of bias. The findings of the evidence review and the 

grades for all important outcomes are shown in Evidence Review Table 15. 

Low-quality evidence suggested that preoperative intra-articular corticosteroid injection did not 

increase the risk of SSI following total joint arthroplasty. This was based on no difference in a 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

62

meta-analysis (N=1146) of 5 OBS studies in TKA149,150 and THA.

151-153

 See individual 

comparators below and in the GRADE table for individual TKA and THA findings. 

Q15.1.a. TKA: Injection vs. no injection

Very low-quality evidence suggested that preoperative intra-articular corticosteroid injection 

did not increase the risk of SSI following TKA. This was based on no difference in SSI, PJI, or 

superficial SSI in meta-analyses (N=414) of 2 OBS studies.

149,150

Both the total number of 

patients and events was small. One study in 144 patients149 suggested that a history of 

preoperative intra-articular injection was significantly associated with PJI after TKA (3 

infections, all in the injection group) while another study in 270 TKAs150 reported no PJIs in 

either group. Both studies had 1 year of follow up. The majority of infections were superficial 

SSIs and no difference was reported at 30 days of follow up. In the smaller study, patients

received injections in the orthopaedic clinic, rheumatology clinic, or general practice setting, 

while those in the larger study all received their injections in the operating room using strict 

aseptic technique. Patients had been injected within 11149 and 12150 months of surgery. 

Q15.1.b. THA: Injection vs. no Injection

Very low-quality evidence suggested that a preoperative intra-articular corticosteroid injection 

did not increase the risk of infection following THA. This was based on no difference in SSI, PJI, 

or superficial SSI on separate meta-analyses of 3 OBS studies.

151-153 No difference in PJI or 

superficial SSI was reported in each individual study. In 2 studies, both the number of patients 

and events was small.

151,153 Corticosteroid doses and follow up periods varied. In each study,

corticosteroid injection was administered in a radiology suite using standard protocols for 

aseptic technique and one study also indicated that the radiologists wore sterile masks and 

gowns.153

Q16. What are the most effective strategies for managing the preoperative use 

of intra-articular corticosteroid injections to reduce the risk of SSI in prosthetic 

joint arthroplasty patients?

Our search did not identify data that evaluated different intra-articular corticosteroid injection 

agents and their impact on risk of SSI.

To answer this question we focused on 2 subquestions: A) Does the length of time between 

corticosteroid injection and prosthetic joint arthroplasty impact the risk of SSI? and B) Does the 

corticosteroid injection dose impact the risk of SSI?

Q16A. Does the length of time between intra-articular corticosteroid injection 

and prosthetic joint arthroplasty impact the risk of SSI?
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

63

The available data evaluated different lengths of time between preoperative intra-articular 

corticosteroid injection and prosthetic joint arthroplasty and the impact on the risk of SSI in 

THA only, not TKA. 

For all comparisons we considered SSI as the critical outcome. The evidence for this question 

consists of 2 OBS studies.152,153 The findings of the evidence review and the grades for all 

important outcomes are shown in Evidence Review Table 16. 

Low-quality evidence suggested no association between the length of time between intraarticular corticosteroid injection and THA and the development of SSI. This was based on no 

difference in the length of time between injection and surgery and the development of SSI in 2 

OBS studies.152,153 The smaller, underpowered study, also reported no association between the 

number of injections and SSI.153 In the larger study, while there was no difference in PJI or 

superficial SSI (mean time between injection and THA was 112 days), the mean time from 

injection to surgery for those diagnosed with PJI was less than half as long those diagnosed 

with superficial SSI (44 vs. 112 days).152

Q16B. Does the corticosteroid injection dose impact the risk of SSI? 

Our search did not identify data that evaluated different doses of preoperative intra-articular 

corticosteroid injections and their impact on the risk of SSI. 

Other Guidelines

While clinical practice guidelines include intra-articular corticosteroid injections among their 

pharmacologic recommendations for the initial management of knee and hip osteoarthritis, 

they do not provide recommendations on management strategies with regard to SSI 

prevention.

258 Safe injection practices apply to the administration of intra-articular 

corticosteroid injections.259 

Q15 and Q16. Recommendation

15 and 16. No recommendation can be made regarding the management of preoperative intraarticular corticosteroid injections for the prevention of surgical site infection in prosthetic joint 

arthroplasty. (No recommendation/ unresolved issue)149-153 (Key questions 15 and 16)

ANTICOAGULATION

Q17. What are the most effective strategies for managing perioperative venous 

thromboembolism (VTE) prophylaxis to reduce the risk of SSI in prosthetic joint 

arthroplasty patients?
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

64

To answer this question we focused on two subquestions: A) Does the risk of SSI differ by 

individual VTE prophylaxis agent? B) What is the optimal timing and duration of perioperative 

VTE prophylaxis that also reduces the risk of SSI in prosthetic joint arthroplasty patients? and C) 

How safe and effective is modifying the dose of the perioperative VTE prophylaxis agent to 

reduce the risk of SSI?

Q17A. Does the risk of SSI differ by individual VTE prophylaxis agent? 

The available data examined the following comparisons between different anticoagulation 

agents:

1. Enoxaparin vs. fondaparinux 

2. Enoxaparin vs. rivaroxaban 

3. Enoxaparin vs. aspirin (ASA) and mechanical prophylaxis

4. Enoxaparin vs. bemiparin vs. fraxiparin vs. fondaparinux

5. LMWHs or fondaparinux vs. ASA

6. Warfarin vs. no pharmacologic or mechanical prophylaxis

7. Warfarin vs. ASA ± mechanical prophylaxis

8. Higher vs. lower mean INR

For all comparisons we considered SSI and PJI as the critical outcomes. Hemorrhagic wound 

complications, time until wound was dry or persistent wound drainage, drug related adverse 

events, and wound hematoma outcomes were also evaluated. The evidence for this question 

consists of 1 SR,154 4 RCTs,

159-162 and 5 OBS163-167 studies in primary and revision, unilateral, THA, 

TKA, and hip fracture procedures. Injectable agents included LMWHs (Factor Xa and some 

thrombin inhibition), most commonly enoxaparin or the indirect Factor Xa inhibitor 

fondaparinux. Oral agents included rivaroxaban (direct Factor Xa inhibitor), warfarin (Vitamin K 

antagonist, Factor II, VII, IX, X inhibitor) and ASA (cyclooxygenase inhibitor). No reversing 

agents currently exist for fondaparinux or rivaroxaban. Our search did not identify studies that 

evaluated warfarin as compared to enoxaparin or the impact of unfractionated heparin, or 

clopidogrel on the risk of SSI. The findings of the evidence review and the grades for all 

important outcomes are shown in Evidence Review Table 17A.

Q17A.1. Enoxaparin vs. fondaparinux 

Low-quality evidence suggested no difference between perioperative injectable VTE 

prophylaxis with enoxaparin or fondaparinux and risk of SSI. This was based on no difference in 

SSI and no drug related adverse events at the end of VTE prophylaxis (11 days) in a large metaanalysis (N=7237) of 4 RCTs (in primary and revision THA, TKA, and hip fracture procedures 

(osteosynthesis and hemi-arthroplasties).154-158 The studies were large, international, multicenter studies evaluating the safety and effectiveness of these agents in reducing the risk of 

postoperative VTE, not SSI. While fondaparinux administration was standardized (2.5mg once a 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

65

day starting postoperatively, except in hip fractures where it was started preoperatively if the 

case was delayed for >24 hours), enoxaparin dose and timing of administration varied between 

studies (30mg twice a day starting postoperatively155,158 or 40 mg once a day starting 

preoperatively156,157). In all four studies, prophylaxis was scheduled to last 5-9 days 

postoperatively. SSI was a secondary outcome and follow up was limited (up to 11 days 

postoperatively). The 4 individual RCTs and the SR meta-analysis were all sponsored by the 

manufacturer of fondaparinux and authored by the same investigators, in which the lead, 

senior, and multiple co-authors reported serving as scientific consultants to the manufacturers 

of both agents evaluated in the studies. Turpie et al., indicated that the sponsor was 

responsible for data collection and final statistical analysis.158

Q17A.2. Enoxaparin vs. rivaroxaban 

High-quality evidence suggested no difference between injectable enoxaparin and oral 

rivaroxaban, and risk of SSI. This was based on no difference in SSI in a large meta-analysis

(N=12,383) of 4 RCTs in elective primary or revision THA or TKA, and no difference in 

hemorrhagic wound complications or drug related adverse events.

159-162 These studies were 

large, international, multi-center studies at low risk of bias, evaluating the safety and 

effectiveness of once daily dosing with enoxaparin or rivaroxaban in reducing the risk of 

postoperative VTE, not SSI. Eriksson et al.,159 and Kakkar et al.,160 compared enoxaparin 40mg 

once a day started preoperatively to rivaroxaban 10mg once a day started postoperatively in 

elective unilateral primary (95%) or revision THA. Rivaroxaban was administered for 35 days in 

both studies; enoxaparin was administered for 35 days in one159 and 10-14 days in the other160. 

Follow up was approximately 2 months. Two other studies evaluated these agents in elective 

unilateral primary (97%) or revision TKA, administered over 10-14 days.

161,162 While rivaroxaban 

administration was standardized (10mg once a day, started preoperatively), enoxaparin dose 

and timing varied between studies (40mg once a day, started preoperatively161 or30mg twice a 

day started postoperatively SSI was a secondary outcome and follow up was approximately 6 

weeks. All studies were sponsored by the manufacturer of rivaroxaban and authored by 

investigators who were employees of the manufacturer or who served as scientific consultants 

to the manufacturers of both agents evaluated in the studies. 

Q17A.3 Enoxaparin vs. ASA and mechanical prophylaxis 

Very low-quality evidence suggested no difference between injectable enoxaparin and

combined oral ASA and mechanical prophylaxis, and risk of SSI. This was based on no increased 

risk of SSI on logistic regression analysis in one large study in primary THA or TKA.

163 Enoxaparin 

was associated with a longer time until wound was dry in THA, but not TKA. Enoxaparin was 

started 12-24 hours postoperatively. ASA 325mg along with pneumatic compression devices 

was started on the morning after surgery. Analysis was limited to patients with a closed suction 

drain and normal coagulation profile. Duration of VTE prophylaxis and follow up period were 

not reported.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

66

Q17A.4. Enoxaparin vs. bemiparin vs. fraxiparin vs. fondaparinux 

Very low-quality evidence suggested no difference between perioperative injectable LMWH, 

ultra LMWH and fondaparinux and risk of SSI. This was based on no difference in PJI at 6 

months of follow up in a small nested, case control study within a larger European multicenter 

prospective study investigating the independent effects of VTE prophylaxis timing on the risk of 

PJI in TKA (low risk of bias).164 Logistic regression analysis suggested that hematoma formation 

increased the risk of PJI four fold. 

Q17A.5. Enoxaparin, dalterparin, tinzaparin or fondaparinux vs. ASA ± mechanical prophylaxis

Very low-quality evidence suggested no difference between perioperative injectable LMWH, 

fondaparinux, and combined oral ASA (with or without mechanical VTE prophylaxis), and risk of 

SSI. This was based on no difference in SSI in a subanalysis (n=41,917) of a very large 

retrospective OBS study (low risk of bias) using administrative data from a national sample of 

primary TKAs.

165 Data were collected from 307 facilities over a 2 year period and compared the 

risk of VTE, bleeding, SSI, and mortality in primary TKA patients 4719 (5.0%) of whom were on 

ASA, 51,923 (55.3%) on oral warfarin, and 37,198 (39.6%) on injectable agents (LMWHs and 

fondaparinux were combined in the analysis). Pneumatic compression devices were used on 

the day of surgery or on the first postoperative day in 1795 (38%), 28,757 (55%), and 17,756 

(48%) of the populations, respectively. Patients on ASA had fewer baseline comorbidities, 

lower baseline risk of venous thromboembolism, and received care in hospitals with shorter 

average length of stay that more commonly discharged to the patient’s home after surgery. 

The study included SSIs detected at the time of admission or upon readmission to the hospital 

within 30 days of the index procedure using International Classification of Diseases, Ninth 

Revision, Clinical Modification (ICD-9-CM) wound infection codes. Authors indicated that 

subtherapeutic dosing and/or inappropriate dose timing of the LMWHs or synthetic Factor Xa 

inhibitor may have impacted the results.

Q17A.6. Warfarin vs. no pharmacologic or mechanical prophylaxis

Very low-quality evidence suggested no difference between oral warfarin VTE prophylaxis and 

no pharmacologic or mechanical prophylaxis, and risk of SSI. This was based on no difference in 

SSI (deep or superficial) in one large retrospective OBS study in primary unilateral TKA at 3 

months of follow up (low risk of bias).166 History of anticoagulation prophylaxis for cardiac 

(arrhythmia or prosthetic valve) or thromboembolic event was not associated with increased 

risk of SSI or gastrointestinal bleed in patients on 6 weeks of postoperative warfarin VTE 

prophylaxis. INR levels (target INR: 1.6-2.2) were monitored and medication adjusted twice 

weekly. Standardized postoperative protocols in both groups included continuous passive 

motion, physical therapy, weight bearing, and similar pain and nausea medications. 

Q17A.7. Warfarin vs. ASA ± mechanical prophylaxis
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

67

Low-quality evidence suggested no difference between perioperative oral warfarin and ASA 

(with or without mechanical VTE prophylaxis), and risk of SSI. This was based on no difference 

in SSI in two large retrospective studies at low risk of bias.

163,165 In one large single institution 

study, logistic regression analysis suggested that in THA and TKA, warfarin (target INR=2) 

started on the day of surgery was not associated with an increased risk of SSI or longer time 

until wound was dry, as compared to ASA 325mg with pneumatic compression devices started 

on the morning after surgery.

163 Duration of VTE prophylaxis and follow up period were not 

reported. Analysis was limited to patients with a closed suction drain and normal coagulation 

profile. A second, large study using administrative data collected from 307 facilities over a 2 

year period suggested no difference in SSI in primary TKAs.

165 Target INR was not reported.

Pneumatic compression devices were used on the day of surgery or on the first postoperative 

day in 55% of patients on warfarin and 38% of patients on ASA. SSIs were detected on

admission or readmission to the hospital within 30 days of the index procedure using 

International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) wound 

infection codes. Authors indicated that subtherapeutic dosing or inappropriate timing may have 

impacted results.

Q17A.8. Higher vs. lower INR

Very low-quality evidence suggested no difference between higher and lower oral warfarin 

INRs, and risk of SSI. This was based on no difference in PJI in a small (N=154) 1:2 case control 

study in primary and revision THA and TKAs (low risk of bias).167 Low dose warfarin (target 

INR=1.5) was administered on the day of surgery and continued for 6 weeks. Thirteen patients 

on anticoagulation therapy preoperatively for a chronic condition, were heparinized 

postoperatively until fully anticoagulated on warfarin with a higher target INR=2-3. All of these 

patients were in the infected cohort. The INR was also significantly higher in patients with 

wound-related problems who later developed infection. In addition, infected patients and 

those with wound complications were more likely to have INR > 1.5 at the time of hospital 

discharge. Infected patients also had a significantly higher incidence of wound hematomas. On 

multivariate logistic regression analysis, wound hematomas and persistent wound drainage 

were significant risk factors for PJI. Nine (69%) of the heparinized patients developed wound 

complications including: hematomas, persistent wound drainage, or delayed wound healing. 

Q17B. What is the optimal timing and duration of perioperative VTE prophylaxis 

that also reduces the risk of SSI?

The available data examined VTE prophylaxis started preoperatively as compared to 

postoperatively in patients receiving injectable LMWHs (enoxaparin, bemiparin, or fraxiparin) 

or fondaparinux.

For this comparison we considered PJI as the critical outcome. The evidence for this question 

consists of 1 OBS study in TKA, at low risk of bias.

164 Our search did not identify data that 

evaluated optimal timing in THA or in patients taking oral agents. Our search did not identify 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

68

data that evaluated optimal duration of perioperative anticoagulation prophylaxis and its 

impact on SSI. The findings of the evidence review and the grades for all important outcomes 

are shown in Evidence Review and GRADE table 17B. 

Very low-quality evidence suggested that close perioperative administration of injectable 

LMWHs or fondaparinux VTE prophylaxis agents did not increase the risk of PJI. This was based 

on no difference in PJI at 6 months of follow up, in a small, nested, multicenter, case control 

study in TKAs.164

Other Guidelines

Clinical practice guidelines, on prevention of VTE in patients undergoing THA, TKA, or hip 

fracture procedures provide recommendations on choice, timing, and duration of VTE 

prophylaxis.

260,261

Q17C.How safe and effective is modifying the dose of perioperative VTE 

prophylaxis agent to reduce the risk of SSI?

Our search did not identify data that evaluated the safety and effectiveness of modifying the 

dose of perioperative VTE prophylaxis agent and its impact on the risk of SSI. 

Q17. Recommendation

17. No recommendation can be made regarding perioperative management of venous 

thromboembolism prophylaxis for the prevention of surgical site infection in prosthetic joint 

arthroplasty. (No recommendation/unresolved issue) 154-167 (Key Question 17)

ORTHOPAEDIC SPACE SUIT

Q18. How safe and effective are orthopaedic space suits in reducing the risk of 

SSI in prosthetic joint arthroplasty patients, and which healthcare personnel 

should wear them?

The available data evaluated the use of a space suit as compared to no space suit.

For this comparison we considered deep SSI requiring reoperation, deep SSI requiring revision,

and deep SSI as the critical outcomes. Superficial SSI outcome was also evaluated. The 

evidence for this question consists of 3 OBS studies at low risk of bias.

168-170 The findings of the 

evidence review and the grades for all important outcomes are shown in Evidence Review Table 

18.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

69

Very-low quality evidence suggested no benefit to using an orthopaedic space suit to reduce 

the risk of SSI. This was based on no difference in deep SSI requiring reoperation,

168 deep SSI 

requiring revision surgery,

169 or deep or superficial SSI170 in 3 OBS studies. The number of 

events for each of these studies was low. The largest national joint registry study with multiple 

subgroup analyses suggested that use of a space suit was associated with an increased number 

of deep SSIs requiring revision surgery within 6 months of THA or TKA, but this evidence was 

limited in size.

169 Results did not differ based on the presence or absence of laminar flow. A 

large multicenter study using administrative data from patients undergoing TKA suggested no 

difference in deep SSIs requiring reoperation within 90 days.

168 Reoperations included incision 

and drainage and implant removal. The definition of deep SSI in this study may have included 

PJI. Space suit and laminar flow use varied between groups. A third small study in THA and hip 

hemiarthroplasties reported only 1 deep SSI in the space suit group and 1 superficial SSI in each 

group at 24 months of follow up.

170 High-efficiency particulate air (HEPA)/mixed turbulent 

filtration was used in both groups. 

Our search did not identify data that quantified potential complications associated with the use 

of space suits. In one large national joint registry study (N=88,311) comments by surgeons 

completing a questionnaire (n=35) included “limited spatial awareness and ease of 

contamination due to an apparent false sense of security” with the use of a space suit.169 We 

did not evaluate the efficacy of the space suit as personal protective equipment.

Also, our search did not identify data that evaluated the association between specific health 

care personnel wearing a space suit and SSI. One retrospective controlled study included a 

surgeon questionnaire reporting that the surgeon, assistant, and scrub nurse were the team 

members wearing a full space suit.169 One prospective controlled study reported those same 

team members wearing the space suit in the intervention group.170

Q18. Recommendation

18. No recommendation can be made regarding the safety and effectiveness of orthopaedic 

space suits or the health care personnel who should wear them for the prevention of surgical 

site infection in prosthetic joint arthroplasty. (No recommendation/unresolved issue)168-170

(Key question 18)

POSTOPERATIVE AMP DURATION IN PROSTHETIC JOINT ARTHROPLASTY 

WITH THE USE OF A DRAIN

Q19. What is the optimal duration of postoperative AMP to reduce the risk of 

SSI in prosthetic joint arthroplasty in the presence of a drain?
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

70

Our search did not identify data that directly evaluated optimal postoperative AMP duration in 

the presence of a drain and its impact on the risk of SSI in prosthetic joint arthroplasty patients.

However, multiple procedures examined in the Core section, Q1.E: Postoperative AMP duration

that included use of a drain (including prosthetic joint arthroplasty procedures) showed no 

benefit of continuing AMP after closing the incision in the operating room. Therefore, the 

broader recommendation for postoperative AMP duration should be applied to prosthetic joint 

arthroplasty procedures irrespective of drain use.

Q19. Recommendation

19. In prosthetic joint arthroplasty, Recommendation 1E applies: In clean and cleancontaminated procedures, do not administer additional prophylactic antimicrobial agent doses 

after the surgical incision is closed in the operating room, even in the presence of a drain. 

(Category IA)27-65 (Key question 19)

BIOFILM

Q20. What are the most effective strategies to reduce the risk of biofilm 

formation and SSI in prosthetic joint arthroplasty patients?

To answer this question we focused on four subquestions: A) How effective are cement 

modifications (i.e., antimicrobial and nanoparticle loading)? B) How effective are prosthesis 

modifications (i.e., antimicrobial coating, galvanic couples, “printing” technologies, and 

nanotechnology)? C) How effective are vaccines? and D) How effective are other biofilm control 

agents (e.g., biofilm dispersants, quorum-sensing inhibitors, novel antimicrobial agents)? 

Q20A. How effective are cement modifications (i.e., antimicrobial and

nanoparticle loading)?

Our search did not identify data that evaluated the safety and effectiveness of cement 

modifications in THA and the risk of SSI. In vitro studies and studies that evaluated 

antimicrobial loaded cement in the absence of perioperative parenteral antimicrobial 

prophylaxis were excluded from our analysis. The available data examined cefuroxime loaded 

cement vs. plain cement in primary TKA patient receiving perioperative AMP.

For this comparison we considered deep SSI as the critical outcome. In these studies, deep SSI 

likely refers to or includes PJI. The evidence for this question consists of 2 RCTs.

171,172 The 

findings of the evidence review and the grades for all important outcomes are shown in 

Evidence Review Table 20A.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

71

Moderate-quality evidence suggested a benefit of cefuroxime loaded cement. This was based 

on a reduced risk of deep SSI in a meta-analysis (N=428) of 2 RCTs: 1 large study in nondiabetic171 patients and 1 small study (N=78) in diabetic 172 patients. Both studies were at 

moderate risk of bias. There were no deep SSIs in the cefuroxime loaded cement groups at an 

average 49 months of follow up. A single surgeon performed all TKAs in an operating room 

without ultraviolet lights, laminar flow, or use of an orthopaedic space suit. Only the tibial and 

patellar components were cemented. Cefuroxime 2g in 40g polymethylmethacrylate cement 

was used in the study groups. AMP included parenteral cefazolin and gentamycin 

preoperatively then every 6 and 12 hours, respectively, postoperatively for 36 hours followed 

by cefazolin orally for 7 more days. Data on organisms isolated from the SSIs and antimicrobial 

resistance were not reported. 

Q20B. How effective are prosthesis surface modifications (i.e., antimicrobial 

coating, galvanic couples, “printing” technologies, and nanotechnology)?

Our search did not identify in vivo studies that evaluated the safety and effectiveness of 

prosthesis modifications and their impact on biofilm formation and the risk of SSI.

Q20C. How effective are vaccines?

Our search did not identify in vivo studies that evaluated the safety and effectiveness of 

vaccines and their impact on biofilm formation and the risk of SSI.

Q20D. How effective are other biofilm control agents (e.g., biofilm dispersants, 

quorum-sensing inhibitors, novel antimicrobial agents)?

Our search did not identify in vivo studies that evaluated the safety and effectiveness of biofilm 

control agents and their impact on biofilm formation and the risk of SSI.

Q20. Recommendations

20A. No recommendation can be made regarding the safety and effectiveness of cement 

modifications and the prevention of biofilm formation or surgical site infection in prosthetic 

joint arthroplasty. (No recommendation/ unresolved issue)

171,172 (Key Question 20A)

20B. No recommendation can be made regarding the safety and effectiveness of prosthesis 

modifications for the prevention of biofilm formation or surgical site infection in prosthetic joint 

arthroplasty. (No recommendation/unresolved issue) (Key Question 20B)

20C. No recommendation can be made regarding the safety and effectiveness of vaccines for 

the prevention of biofilm formation or surgical site infection in prosthetic joint arthroplasty.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

72

(No recommendation/unresolved issue) (Key Question 20C)

20D. No recommendation can be made regarding the safety and effectiveness of biofilm control 

agents such as biofilm dispersants, quorum-sensing inhibitors, or novel antimicrobial agents for 

the prevention of biofilm formation or surgical site infection in prosthetic joint arthroplasty. 

(No recommendation/unresolved issue) (Key Question 20D)
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

73

REFERENCES

1. Centers for Disease Control and Prevention. National Healthcare Safety Network. Surgical Site 

Infection (SSI) Event. 2013; Available at: 

http://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf. Accessed June 17, 2013.

2. McKibben L, Horan T, Tokars JI, et al. Guidance on public reporting of healthcare-associated 

infections: recommendations of the Healthcare Infection Control Practices Advisory Committee. 

American journal of infection control. May 2005;33(4):217-226.

3. Cullen KA, Hall MJ, Golosinskiy A. Ambulatory Surgery in the United States, 2006. National 

health statistics reports; no 11. Revised. 2009; Available at: 

http://www.cdc.gov/nchs/data/nhsr/nhsr011.pdf. Accessed July 24, 2013.

4. DeFrances CJ, Lucas CA, Buie VC, Golosinskiy A. 2006 National Hospital Discharge Survey. 

National health statistics reports; no 5. 2008; Available at: 

http://www.cdc.gov/nchs/data/nhsr/nhsr005.pdf. Accessed July 24, 2013.

5. Fry DE. Fifty ways to cause surgical site infections. Surgical infections. Dec 2011;12(6):497-500.

6. Anderson DJ, Kirkland KB, Kaye KS, et al. Underresourced hospital infection control and 

prevention programs: penny wise, pound foolish? Infection control and hospital epidemiology : 

the official journal of the Society of Hospital Epidemiologists of America. Jul 2007;28(7):767-773.

7. Centers for Disease Control and Prevention. Healthcare-associated Infections. The burden. Scott 

RD II. The direct medical costs of healthcare-associated infections in U.S. hospitals and the 

benefits of prevention. 2009; Available at: 

http://www.cdc.gov/hai/pdfs/hai/scott_costpaper.pdf Accessed July 24, 2013.

8. Stone PW, Braccia D, Larson E. Systematic review of economic analyses of health careassociated infections. American journal of infection control. Nov 2005;33(9):501-509.

9. U.S. Department of Health and Human Services. HHS Action Plan to prevent healthcare 

associated infections: Appendix G. Available at: 

http://www.hhs.gov/ash/initiatives/hai/actionplan/. Accessed July 01, 2013.

10. U.S. Department of Health and Human Services. Centers for Medicare & Medicaid Services. 42 

CFR Parts 412, 413, 415, et al. Medicare Program; Hospital Inpatient Prospective Payment 

Systems for Acute Care Hospitals and the Long-term Care Hospital Prospective Payment System 

Changes and FY2011 Rates; Provider Agreements and Supplier Approvals; and Hospital 

Conditions of Participation for Rehabilitation and Respiratory Care Services; Medicaid Program: 

Accreditation for Providers of Inpatient Psychiatric Services; Final Rule 2010; Available at: 

http://edocket.access.gpo.gov/2010/pdf/2010-19092.pdf. Accessed June 26, 2013.

11. U.S. Government Printing Office. The Deficit Reduction Act of 2005. Available at: 

http://www.gpo.gov/fdsys/pkg/BILLS-109s1932enr/pdf/BILLS-109s1932enr.pdf Accessed June 

17, 2013.

12. Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site infection, 

1999. American journal of infection control. Apr 1999;27(2):97-132; quiz 133-134; discussion 

196.

13. Centers for Disease Control and Prevention. Healthcare Infection Control Practices Advisory 

Committee. Bolyard EA, Tablan OC, Williams W, et. al., Guideline for infection control in health 

care personnel, 1998. 1998; Available at: http://www.cdc.gov/hicpac/pdf/InfectControl98.pdf. 

Accessed June 27, 2013.

14. Centers for Disease Control and Prevention. Healthcare Infection Control Practices Advisory 

Committee. Guidelines for environmental infection control in health-care facilities: 

Recommendations from CDC and the Healthcare Infection Control Practices Advisory Committee 

(HICPAC) MMWR 2003;52(No. RR-10):1–48.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

74

15. Centers for Disease Control and Prevention. Healthcare Infection Contrlol Practices Advisory 

Committee. Rutala WA, Weber DJ. Guideline for disinfection and sterilization in healthcare 

facilities, 2008. 2008; Available at: 

http://www.cdc.gov/hicpac/pdf/guidelines/Disinfection_Nov_2008.pdf. Accessed June 27, 2013.

16. Guyatt GH, Oxman AD, Kunz R, et al. Going from evidence to recommendations. Bmj. May 10 

2008;336(7652):1049-1051.

17. Guyatt GH, Oxman AD, Kunz R, et al. What is "quality of evidence" and why is it important to 

clinicians? Bmj. May 3 2008;336(7651):995-998.

18. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of 

evidence and strength of recommendations. Bmj. Apr 26 2008;336(7650):924-926.

19. Schunemann HJ, Oxman AD, Brozek J, et al. Grading quality of evidence and strength of 

recommendations for diagnostic tests and strategies. Bmj. May 17 2008;336(7653):1106-1110.

20. Centers for Disease Control and Prevention. Healthcare Infection Control Practices Advisory 

Committee. Umscheid CA, Agarwal RK, Brennan PJ. Updating the guideline methodology of the 

Healthcare Infection Control Practices Advisory Committee (HICPAC). 2010; Available at: 

http://www.cdc.gov/hicpac/pdf/guidelines/2009-10-29HICPAC_GuidelineMethodsFINAL.pdf. 

Accessed July 03, 2013.

21. Umscheid CA, Agarwal RK, Brennan PJ, Healthcare Infection Control Practices Advisory C. 

Updating the guideline development methodology of the Healthcare Infection Control Practices 

Advisory Committee (HICPAC). American journal of infection control. May 2010;38(4):264-273.

22. Costantine MM, Rahman M, Ghulmiyah L, et al. Timing of perioperative antibiotics for cesarean 

delivery: a metaanalysis. Am J Obstet Gynecol. Sep 2008;199(3).

23. Sullivan SA, Smith T, Chang E, Hulsey T, Vandorsten JP, Soper D. Administration of cefazolin prior 

to skin incision is superior to cefazolin at cord clamping in preventing postcesarean infectious 

morbidity: a randomized, controlled trial. Am J Obstet Gynecol. May 2007;196(5):455 e451-455.

24. Thigpen BD, Hood WA, Chauhan S, et al. Timing of prophylactic antibiotic administration in the 

uninfected laboring gravida: a randomized clinical trial. Am J Obstet Gynecol. Jun 

2005;192(6):1864-1868; discussion 1868-1871.

25. Wax JR, Hersey K, Philput C, et al. Single dose cefazolin prophylaxis for postcesarean infections: 

before vs. after cord clamping. The Journal of maternal-fetal medicine. Jan-Feb 1997;6(1):61-65.

26. Cuthbertson AM, McLeish AR, Penfold JC, Ross H. A comparison between single and double dose 

intravenous Timentin for the prophylaxis of wound infection in elective colorectal surgery. 

Diseases of the colon and rectum. Feb 1991;34(2):151-155.

27. Tamayo E, Gualis J, Florez S, Castrodeza J, Eiros Bouza JM, Alvarez FJ. Comparative study of 

single-dose and 24-hour multiple-dose antibiotic prophylaxis for cardiac surgery. The Journal of 

thoracic and cardiovascular surgery. Dec 2008;136(6):1522-1527.

28. Conte JE, Jr., Cohen SN, Roe BB, Elashoff RM. Antibiotic prophylaxis and cardiac surgery. A 

prospective double-blind comparison of single-dose versus multiple-dose regimens. Annals of 

internal medicine. Jun 1972;76(6):943-949.

29. Austin TW, Coles JC, Burnett R, Goldbach M. Aortocoronary bypass procedures and sternotomy 

infections: a study of antistaphylococcal prophylaxis. Canadian journal of surgery. Journal 

canadien de chirurgie. Sep 1980;23(5):483-485.

30. Nooyen SM, Overbeek BP, Brutel de la Riviere A, Storm AJ, Langemeyer JJ. Prospective 

randomised comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in 

coronary artery bypass grafting. Eur J Clin Microbiol Infect Dis. Dec 1994;13(12):1033-1037.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

75

31. Bernard A, Pillet M, Goudet P, Viard H. Antibiotic-prophylaxis in pulmonary surgery - a 

prospective randomized double-blind trial of flash cefuroxime versus 48-hour cefuroxime. J 

Thorac Cardiov Sur. Mar 1994;107(3):896-900.

32. Oostvogel HJ, van Vroonhoven TJ, van der Werken C, Lenderink AW. Single-dose v. short-term 

antibiotic therapy for prevention of wound infection in general surgery. A prospective, 

randomized double-blind trial. Acta chirurgica Scandinavica. Oct 1987;153(10):571-575.

33. Hall JC, Christiansen KJ, Goodman M, et al. Duration of antimicrobial prophylaxis in vascular 

surgery. American journal of surgery. Feb 1998;175(2):87-90.

34. Hasselgren PO, Ivarsson L, Risberg B, Seeman T. Effects of prophylactic antibiotics in vascular 

surgery. A prospective, randomized, double-blind study. Annals of surgery. Jul 1984;200(1):86-

92.

35. Carroll WR, Rosenstiel D, Fix JR, et al. Three-dose vs extended-course clindamycin prophylaxis 

for free-flap reconstruction of the head and neck. Arch Otolaryngol Head Neck Surg. Jul 

2003;129(7):771-774.

36. Liu SA, Tung KC, Shiao JY, Chiu YT. Preliminary report of associated factors in wound infection 

after major head and neck neoplasm operations--does the duration of prophylactic antibiotic 

matter? J Laryngol Otol. Apr 2008;122(4):403-408.

37. Hemsell DL, Heard ML, Nobles BJ, Hemsell PG. Single-dose cefoxitin prophylaxis for 

premenopausal women undergoing vaginal hysterectomy. Obstetrics and gynecology. Mar 

1984;63(3):285-290.

38. Turano A. New clinical data on the prophylaxis of infections in abdominal, gynecologic, and 

urologic surgery. Multicenter Study Group. American journal of surgery. Oct 1992;164(4A 

Suppl):16S-20S.

39. Mayer HO, Petru E, Haas J, Heydarfadai M. Perioperative antibiotic prophylaxis in patients 

undergoing radical surgery for gynecologic cancer: single dose versus multiple dose 

administration. European journal of gynaecological oncology. 1993;14(3):177-181.

40. Su HY, Ding DC, Chen DC, Lu MF, Liu JY, Chang FY. Prospective randomized comparison of singledose versus 1-day cefazolin for prophylaxis in gynecologic surgery. Acta Obstet Gynecol Scand. 

Apr 2005;84(4):384-389.

41. Chang WC, Hung YC, Li TC, Yang TC, Chen HY, Lin CC. Short course of prophylactic antibiotics in 

laparoscopically assisted vaginal hysterectomy. J Reprod Med. Jul 2005;50(7):524-528.

42. Gatell JM, Garcia S, Lozano L, Soriano E, Ramon R, SanMiguel JG. Perioperative cefamandole 

prophylaxis against infections. The Journal of bone and joint surgery. American volume. Oct 

1987;69(8):1189-1193.

43. Buckley R, Hughes GNF, Snodgrass T, Huchcroft SA. Perioperative cefazolin prophylaxis in hip 

fracture surgery. Can J Surg. Apr 1990;33(2):122-127.

44. Garotta F, Pamparana F. Antimicrobial prophylaxis with ceftizoxime versus cefuroxime in 

orthopedic surgery. Ceftizoxime Orthopedic Surgery Italian Study Group. Journal of 

chemotherapy. Feb 1991;3 Suppl 2:34-35.

45. Ali M, Raza A. Role of single dose antibiotic prophylaxis in clean orthopedic surgery. Journal of 

the College of Physicians and Surgeons--Pakistan : JCPSP. Jan 2006;16(1):45-48.

46. Ritter MA, Campbell E, Keating EM, Faris PM. Comparison of intraoperative versus 24 hour 

antibiotic prophylaxis in total joint replacement. A controlled prospective study. Orthopaedic 

review. Jun 1989;18(6):694-696.

47. Wymenga AB, Hekster YA, Theeuwes A, Muytjens HL, van Horn JR, Slooff TJ. Antibiotic use after 

cefuroxime prophylaxis in hip and knee joint replacement. Clinical pharmacology and 

therapeutics. Aug 1991;50(2):215-220.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

76

48. Suzuki T, Sadahiro S, Maeda Y, Tanaka A, Okada K, Kamijo A. Optimal duration of prophylactic 

antibiotic administration for elective colon cancer surgery: A randomized, clinical trial. Surgery. 

Feb 2011;149(2):171-178.

49. Becker JM, Alexander DP. Colectomy, mucosal proctectomy, and ileal pouch-anal anastomosis. A 

prospective trial of optimal antibiotic management. Annals of surgery. Mar 1991;213(3):242-

247.

50. Carr ND, Hobbiss J, Cade D, Schofield PF. Metronidazole in the prevention of wound sepsis after 

elective colorectal surgery. Journal of the Royal College of Surgeons of Edinburgh. May 

1984;29(3):139-142.

51. Grundmann R, Burkardt F, Scholl H, Koelschbach D. One versus three doses of 

metronidazole/mezlocillin for antibiotic prophylaxis in colon surgery. Chemioterapia : 

international journal of the Mediterranean Society of Chemotherapy. Jun 1987;6(2 Suppl):604-

605.

52. Kow L, Toouli J, Brookman J, McDonald PJ. Comparison of cefotaxime plus metronidazole versus 

cefoxitin for prevention of wound infection after abdominal surgery. World journal of surgery. 

Sep-Oct 1995;19(5):680-686; discussion 686.

53. Fujita S, Saito N, Yamada T, et al. Randomized, multicenter trial of antibiotic prophylaxis in 

elective colorectal surgery: single dose vs 3 doses of a second-generation cephalosporin without 

metronidazole and oral antibiotics. Archives of surgery. Jul 2007;142(7):657-661.

54. Juul P, Klaaborg KE, Kronborg O. Single or multiple doses of metronidazole and ampicillin in 

elective colorectal surgery. A randomized trial. Diseases of the colon and rectum. Jul 

1987;30(7):526-528.

55. Mendel V, Jung D, Heymann H. Single-shot antibiotic prophylaxis in colon surgery. 

Chemioterapia : international journal of the Mediterranean Society of Chemotherapy. Jun 

1987;6(2 Suppl):597-600.

56. Hall JC, Watts JM, Press L, O'Brien P, Turnidge J, McDonald P. Single-dose antibiotic prophylaxis 

in contaminated abdominal surgery. Archives of surgery. Feb 1989;124(2):244-247.

57. Bates T, Roberts JV, Smith K, German KA. A randomized trial of one versus three doses of 

Augmentin as wound prophylaxis in at-risk abdominal surgery. Postgraduate medical journal. 

Oct 1992;68(804):811-816.

58. Wenzel M, Heinrich M, Schmidt C. Peri-operative infection prophylaxis with ornidazole and 

gentamicin in elective colonic surgery. Pharmatherapeutica. 1985;4(6):351-355.

59. Moesgaard F, Lykkegaard-Nielsen M. Preoperative cell-mediated immunity and duration of 

antibiotic prophylaxis in relation to postopertive infectious complications. A controlled trial in 

biliary, gastroduodenal and colorectal surgery. Acta chirurgica Scandinavica. Apr-May 

1989;155(4-5):281-286.

60. Karran SJ, Sutton G, Gartell P, Karran SE, Finnis D, Blenkinsop J. Imipenem prophylaxis in elective 

colorectal surgery. The British journal of surgery. Sep 1993;80(9):1196-1198.

61. McArdle CS, Morran CG, Pettit L, Gemmell CG, Sleigh JD, Tillotson GS. Value of oral antibiotic 

prophylaxis in colorectal surgery. The British journal of surgery. Aug 1995;82(8):1046-1048.

62. Mui LM, Ng CS, Wong SK, et al. Optimum duration of prophylactic antibiotics in acute nonperforated appendicitis. ANZ J Surg. Jun 2005;75(6):425-428.

63. Aberg C, Thore M. Single versus triple dose antimicrobial prophylaxis in elective abdominal 

surgery and the impact on bacterial ecology. The Journal of hospital infection. Jun 

1991;18(2):149-154.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

77

64. Mohri Y, Tonouchi H, Kobayashi M, Nakai K, Kusunoki M, Mie Surgical Infection Research G. 

Randomized clinical trial of single- versus multiple-dose antimicrobial prophylaxis in gastric 

cancer surgery. The British journal of surgery. Jun 2007;94(6):683-688.

65. Togo S, Tanaka K, Matsuo K, et al. Duration of antimicrobial prophylaxis in patients undergoing 

hepatectomy: a prospective randomized controlled trial using flomoxef. J Antimicrob 

Chemother. May 2007;59(5):964-970.

66. Charalambous C. When should old therapies be abandoned? A modern look at old studies on 

topical ampicillin. J Infection. Oct 2003;47(3):203-209.

67. Kamath S, Sinha S, Shaari E, Young D, Campbell AC. Role of topical antibiotics in hip surgeries - A 

prospective randomised study. Injury. Jun 2005;36(6):783-787.

68. Neri V, Fersini A, Ambrosi A, Tartaglia N, Valentino TP. Umbilical port-site complications in 

laparoscopic cholecystectomy: role of topical antibiotic therapy. Jsls-J Soc Laparoend. Apr-Jun 

2008;12(2):126-132.

69. Al-Shehri MY, Saif S, Ibrahim A, et al. Topical ampicillin for prophylaxis against wound infection 

in acute appendicitis. Annals of Saudi medicine. May 1994;14(3):233-236.

70. Juul P, Merrild U, Kronborg O. Topical ampicillin in addition to a systemic antibiotic prophylaxis 

in elective colorectal surgery. A prospective randomized study. Diseases of the colon and 

rectum. Nov 1985;28(11):804-806.

71. Raahave D, Hesselfeldt P, Pedersen T, Zachariassen A, Kann D, Hansen OH. No effect of topical 

ampicillin prophylaxis in elective operations of the colon or rectum. Surgery, gynecology & 

obstetrics. Feb 1989;168(2):112-114.

72. Seco JL, Ojeda E, Reguilon C, et al. Combined topical and systemic antibiotic prophylaxis in acute 

appendicitis. American journal of surgery. Feb 1990;159(2):226-230.

73. Almdahl SM, Veel T, Halvorsen P, Vold MB, Molstad P. Randomized prospective trial of 

saphenous vein harvest site infection after wound closure with and without topical application 

of autologous platelet-rich plasma. Eur J Cardiothorac Surg. Jan 2011;39(1):44-48.

74. Litmathe J, Philipp C, Kurt M, Boeken U, Gams E, Feindt P. The use of autologous platelet gel 

(APG) for high-risk patients in cardiac surgery - is it beneficial? Perfusion-Uk. Nov 

2009;24(6):381-387.

75. Peerbooms JC, de Wolf GS, Colaris JW, Bruijn DJ, Verhaar JAN. No positive effect of autologous 

platelet gel after total knee arthroplasty A double-blind randomized controlled trial: 102 

patients with a 3-month follow-up. Acta Orthop. 2009;80(5):557-562.

76. Zhang ZT, Zhang HW, Fang XD, et al. Cosmetic outcome and surgical site infection rates of 

antibacterial absorbable (Polyglactin 910) suture compared to Chinese silk suture in breast 

cancer surgery: a randomized pilot research. Chin Med J (Engl). Mar 2011;124(5):719-724.

77. Mingmalairak C, Ungbhakorn P, Paocharoen V. Efficacy of antimicrobial coating suture coated 

polyglactin 910 with tricosan (Vicryl plus) compared with polyglactin 910 (Vicryl) in reduced 

surgical site infection of appendicitis, double blind randomized control trial, preliminary safety 

report. J Med Assoc Thai. Jun 2009;92(6):770-775.

78. Rozzelle CJ, Leonardo J, Li V. Antimicrobial suture wound closure for cerebrospinal fluid shunt 

surgery: a prospective, double-blinded, randomized controlled trial. J Neurosurg Pediatr. Aug 

2008;2(2):111-117.

79. Ford HR, Jones P, Gaines B, Reblock K, Simpkins DL. Intraoperative handling and wound healing: 

controlled clinical trial comparing coated VICRYL plus antibacterial suture (coated polyglactin 

910 suture with triclosan) with coated VICRYL suture (coated polyglactin 910 suture). Surgical 

infections. Fall 2005;6(3):313-321.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

78

80. Gandhi GY, Nuttall GA, Abel MD, et al. Intensive intraoperative insulin therapy versus 

conventional glucose management during cardiac surgery: a randomized trial. Annals of internal 

medicine. Feb 20 2007;146(4):233-243.

81. Chan RP, Galas FR, Hajjar LA, Bello CN, Piccioni MA, Auler JO, Jr. Intensive perioperative glucose 

control does not improve outcomes of patients submitted to open-heart surgery: a randomized 

controlled trial. Clinics. 2009;64(1):51-60.

82. Melling AC, Ali B, Scott EM, Leaper DJ. Effects of preoperative warming on the incidence of 

wound infection after clean surgery: a randomised controlled trial. Lancet. Sep 15 

2001;358(9285):876-880.

83. Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgicalwound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. 

The New England journal of medicine. May 9 1996;334(19):1209-1215.

84. Wong PF, Kumar S, Bohra A, Whetter D, Leaper DJ. Randomized clinical trial of perioperative 

systemic warming in major elective abdominal surgery. The British journal of surgery. Apr 

2007;94(4):421-426.

85. Belda FJ, Aguilera L, Garcia de la Asuncion J, et al. Supplemental perioperative oxygen and the 

risk of surgical wound infection: a randomized controlled trial. JAMA. Oct 26 2005;294(16):2035-

2042.

86. Bickel A, Gurevits M, Vamos R, Ivry S, Eitan A. Perioperative hyperoxygenation and wound site 

infection following surgery for acute appendicitis: a randomized, prospective, controlled trial. 

Archives of surgery. Apr 2011;146(4):464-470.

87. Greif R, Akca O, Horn EP, Kurz A, Sessler DI, Outcomes Research G. Supplemental perioperative 

oxygen to reduce the incidence of surgical-wound infection. The New England journal of 

medicine. Jan 20 2000;342(3):161-167.

88. Meyhoff CS, Wetterslev J, Jorgensen LN, et al. Effect of High Perioperative Oxygen Fraction on 

Surgical Site Infection and Pulmonary Complications After Abdominal Surgery The PROXI 

Randomized Clinical Trial. Jama-Journal of the American Medical Association. Oct 14 

2009;302(14):1543-1550.

89. Staehr AK, Meyhoff CS, Rasmussen LS, Group PT. Inspiratory oxygen fraction and postoperative 

complications in obese patients: a subgroup analysis of the PROXI trial. Anesthesiology. Jun 

2011;114(6):1313-1319.

90. Pryor KO, Fahey TJ, 3rd, Lien CA, Goldstein PA. Surgical site infection and the routine use of 

perioperative hyperoxia in a general surgical population: a randomized controlled trial. JAMA. 

Jan 7 2004;291(1):79-87.

91. Gardella C, Goltra LB, Laschansky E, et al. High-concentration supplemental perioperative 

oxygen to reduce the incidence of postcesarean surgical site infection: a randomized controlled 

trial. Obstetrics and gynecology. Sep 2008;112(3):545-552.

92. Turtiainen J, Saimanen EI, Partio TJ, et al. Supplemental postoperative oxygen in the prevention 

of surgical wound infection after lower limb vascular surgery: a randomized controlled trial. 

World journal of surgery. Jun 2011;35(6):1387-1395.

93. Whitney JD, Heiner S, Mygrant BI, Wood C. Tissue and wound healing effects of short duration 

postoperative oxygen therapy. Biol Res Nurs. Jan 2001;2(3):206-215.

94. Webster J, Osborne S. Preoperative bathing or showering with skin antiseptics to prevent 

surgical site infection. Cochrane Database of Systematic Reviews. 2007(2):CD004985.

95. Byrne DJ NA, Cuschieri A. The value of whole body disinfection in the prevention of 

postoperative wound infection in clean and potentially contaminated surgery. A prospective, 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

79

randomised, double-blind placebo-controlled clinical trial. Surgical Research Communications. 

1992;12(1):43-52.

96. Earnshaw JJ, Berridge DC, Slack RC, Makin GS, Hopkinson BR. Do preoperative chlorhexidine 

baths reduce the risk of infection after vascular reconstruction? European journal of vascular 

surgery. Aug 1989;3(4):323-326.

97. Hayek LJ, Emerson JM, Gardner AM. A placebo-controlled trial of the effect of two preoperative 

baths or showers with chlorhexidine detergent on postoperative wound infection rates. The 

Journal of hospital infection. Sep 1987;10(2):165-172.

98. Randall PE, Ganguli L, Marcuson RW. Wound infection following vasectomy. British journal of 

urology. Oct 1983;55(5):564-567.

99. Rotter ML, Larsen SO, Cooke EM, et al. A comparison of the effects of preoperative whole-body 

bathing with detergent alone and with detergent containing chlorhexidine gluconate on the 

frequency of wound infections after clean surgery. Journal of Hospital Infection. May 

1988;11(4):310-320.

100. Veiga DF, Damasceno CA, Veiga-Filho J, et al. Randomized controlled trial of the effectiveness of 

chlorhexidine showers before elective plastic surgical procedures. Infection Control and Hospital 

Epidemiology: the Official Journal of the Society of Hospital Epidemiologists of America. Jan 

2009;30(1):77-79.

101. Wihlborg O. The effect of washing with chlorhexidine soap on wound infection rate in general 

surgery. A controlled clinical study. Annales chirurgiae et gynaecologiae. 1987;76(5):263-265.

102. Veiga DF, Damasceno CA, Veiga Filho J, et al. Influence of povidone-iodine preoperative showers 

on skin colonization in elective plastic surgery procedures. Plast Reconstr Surg. Jan 

2008;121(1):115-118; discussion 119-120.

103. Ellenhorn JD, Smith DD, Schwarz RE, et al. Paint-only is equivalent to scrub-and-paint in 

preoperative preparation of abdominal surgery sites. Journal of the American College of 

Surgeons. Nov 2005;201(5):737-741.

104. Segal CG, Anderson JJ. Preoperative skin preparation of cardiac patients. AORN Journal: 

Association of periOperative Registered Nurses Journal. Nov 2002;76(5):821-828.

105. Hort KR, DeOrio JK. Residual bacterial contamination after surgical preparation of the foot or 

ankle with or without alcohol. Foot & ankle international / American Orthopaedic Foot and Ankle 

Society [and] Swiss Foot and Ankle Society. Oct 2002;23(10):946-948.

106. Gilliam DL, Nelson CL. Comparison of a one-step iodophor skin preparation versus traditional 

preparation in total joint surgery. Clinical orthopaedics and related research. Jan 1990(250):258-

260.

107. Saltzman MD, Nuber GW, Gryzlo SM, Marecek GS, Koh JL. Efficacy of surgical preparation 

solutions in shoulder surgery. The Journal of bone and joint surgery. American volume. Aug 

2009;91(8):1949-1953.

108. Roberts A, Wilcox K, Devineni R, Harris R, Osevala M. Skin preparation in CABG surgery: a 

prospective randomized trial. Complications in Surgery. 1995;14(6):724, 741-724, 747.

109. Sistla SC, Prabhu G, Sistla S, Sadasivan J. Minimizing wound contamination in a 'clean' surgery: 

comparison of chlorhexidine-ethanol and povidone-iodine. Chemotherapy. 2010;56(4):261-267.

110. Darouiche RO, Wall MJ, Jr., Itani KM, et al. Chlorhexidine-alcohol versus povidone-iodine for 

surgical-site antisepsis. The New England journal of medicine. Jan 7 2010;362(1):18-26.

111. Bibbo C, Patel DV, Gehrmann RM, Lin SS. Chlorhexidine provides superior skin decontamination 

in foot and ankle surgery: a prospective randomized study. Clinical Orthopaedics & Related 

Research. Sep 2005;438:204-208.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

80

112. Paocharoen V, Mingmalairak C, Apisarnthanarak A. Comparison of surgical wound infection after 

preoperative skin preparation with 4% chlorhexidine [correction of chlohexidine] and povidone 

iodine: a prospective randomized trial. Journal of the Medical Association of Thailand = 

Chotmaihet thangphaet. Jul 2009;92(7):898-902.

113. Cheng K, Robertson H, St Mart JP, Leanord A, McLeod I. Quantitative analysis of bacteria in 

forefoot surgery: a comparison of skin preparation techniques. Foot & ankle international / 

American Orthopaedic Foot and Ankle Society [and] Swiss Foot and Ankle Society. Oct 

2009;30(10):992-997.

114. Veiga DF, Damasceno CAV, Veiga J, et al. Povidone iodine versus chlorhexidine in skin antisepsis 

before elective plastic surgery procedures: a randomized controlled trial. Plast Reconstr Surg. 

Nov 2008;122(5):170e-171e.

115. Berry AR, Watt B, Goldacre MJ, Thomson JW, McNair TJ. A comparison of the use of povidoneiodine and chlorhexidine in the prophylaxis of postoperative wound infection. The Journal of 

hospital infection. Mar 1982;3(1):55-63.

116. Ostrander RV, Botte MJ, Brage ME. Efficacy of surgical preparation solutions in foot and ankle 

surgery. The Journal of bone and joint surgery. American volume. May 2005;87(5):980-985.

117. Iyer A, Gilfillan I, Thakur S, Sharma S. Reduction of surgical site infection using a microbial 

sealant: a randomized trial. The Journal of thoracic and cardiovascular surgery. Aug 

2011;142(2):438-442.

118. von Eckardstein AS, Lim CH, Dohmen PM, et al. A randomized trial of a skin sealant to reduce the 

risk of incision contamination in cardiac surgery. The Annals of thoracic surgery. Aug 

2011;92(2):632-637.

119. Towfigh S, Cheadle WG, Lowry SF, Malangoni MA, Wilson SE. Significant reduction in incidence 

of wound contamination by skin flora through use of microbial sealant. Archives of surgery. Sep 

2008;143(9):885-891; discussion 891.

120. Ward HRG, Jennings OGN, Potgieter P, Lombard CJ. Do plastic adhesive drapes prevent post 

caesarean wound infection? Journal of Hospital Infection. Mar 2001;47(3):230-234.

121. Chiu KY, Lau SK, Fung B, Ng KH, Chow SP. Plastic adhesive drapes and wound infection after hip 

fracture surgery. The Australian & New Zealand Journal of Surgery. Oct 1993;63(10):798-801.

122. Jackson DW, Pollock AV, Tindal DS. The value of a plastic adhesive drape in the prevention of 

wound infection. A controlled trial. Br J Surg. May 1971;58(5):340-342.

123. Psaila JV, Wheeler MH, Crosby DL. The role of plastic wound drapes in the prevention of wound 

infection following abdominal surgery. Br J Surg. Oct 1977;64(10):729-732.

124. Dewan PA, Van Rij AM, Robinson RG, Skeggs GB, Fergus M. The use of an iodophor-impregnated 

plastic incise drape in abdominal surgery--a controlled clinical trial. Aust N Z J Surg. Nov 

1987;57(11):859-863.

125. 14756 Chang FY, Chang MC, Wang ST, Yu WK, Liu CL, Chen TH. Can povidone-iodine solution be 

used safely in a spinal surgery? European spine journal : official publication of the European 

Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical 

Spine Research Society. Jun 2006;15(6):1005-1014.

126. Cheng MT, Chang MC, Wang ST, Yu WK, Liu CL, Chen TH. Efficacy of dilute betadine solution 

irrigation in the prevention of postoperative infection of spinal surgery. Spine. Aug 1 

2005;30(15):1689-1693.

127. Sindelar WF, Mason GR. Irrigation of subcutaneous tissue with povidone-iodine solution for 

prevention of surgical wound infections. Surgery, gynecology & obstetrics. Feb 1979;148(2):227-

231.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

81

128. Rogers DM, Blouin GS, O'Leary JP. Povidone-iodine wound irrigation and wound sepsis. Surgery, 

gynecology & obstetrics. Nov 1983;157(5):426-430.

129. Sindelar WF, Mason GR. Intraperitoneal irrigation with povidone-iodine solution for the 

prevention of intra-abdominal abscesses in the bacterially contaminated abdomen. Surgery, 

gynecology & obstetrics. Mar 1979;148(3):409-411.

130. Vallance S, Waldron R. Antiseptic vs. saline lavage in purulent and faecal peritonitis. The Journal 

of hospital infection. Mar 1985;6 Suppl A:87-91.

131. Sindelar WF, Brower ST, Merkel AB, Takesue EI. Randomised trial of intraperitoneal irrigation 

with low molecular weight povidone-iodine solution to reduce intra-abdominal infectious 

complications. The Journal of hospital infection. Mar 1985;6 Suppl A:103-114.

132. Harihara Y, Konishi T, Kobayashi H, et al. Effects of applying povidone-iodine just before skin 

closure. Dermatology. 2006;212:53-57.

133. Frietsch T, Karger R, Scholer M, et al. Leukodepletion of autologous whole blood has no impact 

on perioperative infection rate and length of hospital stay. Transfusion. Oct 2008;48(10):2133-

2142.

134. Frietsch T, Krombholz K, Tolksdorf B, Nebe T, Segiet W, Lorentz A. Cellular immune response to 

autologous blood transfusion in hip arthroplasty: whole blood versus buffy coat-poor packed red 

cells and fresh-frozen plasma. Vox Sang. Oct 2001;81(3):187-193.

135. Innerhofer P, Klingler A, Klimmer C, Fries D, Nussbaumer W. Risk for postoperative infection 

after transfusion of white blood cell-filtered allogeneic or autologous blood components in 

orthopedic patients undergoing primary arthroplasty. Transfusion. Jan 2005;45(1):103-110.

136. Rosencher N, Kerkkamp HEM, Macheras G, et al. Orthopedic Surgery Transfusion Hemoglobin 

European Overview (OSTHEO) study: blood management in elective knee and hip arthroplasty in 

Europe. Transfusion. Apr 2003;43(4):459-469.

137. Weber EW, Slappendel R, Prins MH, van der Schaaf DB, Durieux ME, Strumper D. Perioperative 

blood transfusions and delayed wound healing after hip replacement surgery: effects on 

duration of hospitalization. Anesthia and Analgesia. May 2005;100(5):1416-1421, table of 

contents.

138. Llewelyn CA, Taylor RS, Todd AAM, et al. The effect of universal leukoreduction on postoperative 

infections and length of hospital stay in elective orthopedic and cardiac surgery. Transfusion. 

Apr 2004;44(4):489-500.

139. Pedersen AB, Mehnert F, Overgaard S, Johnsen SP. Allogeneic blood transfusion and prognosis 

following total hip replacement: a population-based follow up study. BMC Musculoskeletal 

Disorders. Dec 29 2009;10.

140. del Trujillo MM, Carrero A, Munoz M. The utility of the perioperative autologous transfusion 

system OrthoPAT (R) in total hip replacement surgery: a prospective study. Arch Orthop Traum 

Su. Oct 2008;128(10):1031-1038.

141. Borghi B, Casati A, Anaesthesia RSGoO. Incidence and risk factors for allogenic blood transfusion 

during major joint replacement using an integrated autotransfusion regimen. European Journal 

of Anaesthesiology. Jul 2000;17(7):411-417.

142. Kawakami K, Ikari K, Kawamura K, et al. Complications and features after joint surgery in 

rheumatoid arthritis patients treated with tumour necrosis factor-alpha blockers: perioperative 

interruption of tumour necrosis factor-alpha blockers decreases complications? Rheumatology. 

Feb 2010;49(2):341-347.

143. Momohara S, Kawakami K, Iwamoto T, et al. Prosthetic joint infection after total hip or knee 

arthroplasty in rheumatoid arthritis patients treated with nonbiologic and biologic diseasemodifying antirheumatic drugs. Mod Rheumatol. Oct 2011;21(5):469-475.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

82

144. Hirano Y, Kojima T, Kanayama Y, et al. Influences of anti-tumour necrosis factor agents on 

postoperative recovery in patients with rheumatoid arthritis. Clin Rheumatol. May 

2010;29(5):495-500.

145. Perhala RS, Wilke WS, Clough JD, Segal AM. Local infectious complications following large joint 

replacement in rheumatoid arthritis patients treated with methotrexate versus those not 

treated with methotrexate. Arthritis Rheum. Feb 1991;34(2):146-152.

146. Carpenter MT, West SG, Vogelgesang SA, Casey Jones DE. Postoperative joint infections in 

rheumatoid arthritis patients on methotrexate therapy. Orthopedics. Mar 1996;19(3):207-210.

147. Bridges SL, Jr., Lopez-Mendez A, Han KH, Tracy IC, Alarcon GS. Should methotrexate be 

discontinued before elective orthopedic surgery in patients with rheumatoid arthritis? J 

Rheumatol. Jul 1991;18(7):984-988.

148. Bongartz T, Halligan CS, Osmon DR, et al. Incidence and risk factors of prosthetic joint infection 

after total hip or knee replacement in patients with rheumatoid arthritis. Arthrit Rheum-Arthr. 

Dec 15 2008;59(12):1713-1720.

149. Papavasiliou AV, Isaac DL, Marimuthu R, Skyrme A, Armitage A. Infection in knee replacements 

after previous injection of intra-articular steroid. Journal of Bone and Joint Surgery. British 

Volume. Mar 2006;88B(3):321-323.

150. Desai A, Ramankutty S, Board T, Raut V. Does intraarticular steroid infiltration increase the rate 

of infection in subsequent total knee replacements? Knee. Aug 2009;16(4):262-264.

151. Sreekumar R, Venkiteswaran R, Raut V. Infection in primary hip arthroplasty after previous 

steroid infiltration. Int Orthop. Feb 2007;31(1):125-128.

152. McIntosh AL, Hanssen AD, Wenger DE, Osmon DR. Recent intraarticular steroid injection may 

increase infection rates in primary THA. Clinical orthopaedics and related research. Oct 

2006;451:50-54.

153. Kaspar S, de Beer JD. Infection in hip arthroplasty after previous injection of steroid. Journal of 

Bone and Joint Surgery-British Volume. Apr 2005;87B(4):454-457.

154. Turpie AGG, Bauer KA, Eriksson BL, Lassen MR, Studies SCotPOP. Fondaparinux vs enoxaparin for 

the prevention of venous thromboembolism in major orthopedic surgery - A meta-analysis of 4 

randomized double-blind studies. Arch Intern Med. Sep 9 2002;162(16):1833-1840.

155. Bauer KA, Eriksson BI, Lassen MR, Turpie AG, Study SCotPiMKS. Fondaparinux compared with 

enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. 

The New England journal of medicine. Nov 1 2001;345(18):1305-1310.

156. Eriksson BI, Bauer KA, Lassen MR, Turpie AG, Steering Committee of the Pentasaccharide in HipFracture Surgery S. Fondaparinux compared with enoxaparin for the prevention of venous 

thromboembolism after hip-fracture surgery. New England Journal of Medicine. Nov 1 

2001;345(18):1298-1304.

157. Lassen MR, Bauer KA, Eriksson BI, Turpie AG, European Pentasaccharide Elective Surgery Study 

Steering C. Postoperative fondaparinux versus preoperative enoxaparin for prevention of 

venous thromboembolism in elective hip-replacement surgery: a randomised double-blind 

comparison. Lancet. May 18 2002;359(9319):1715-1720.

158. Turpie AG, Bauer KA, Eriksson BI, Lassen MR, Pentathalon Study Steering Committee. 

Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous 

thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. 

Lancet. May 18 2002;359(9319):1721-1726.

159. Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis 

after hip arthroplasty. The New England journal of medicine. Jun 26 2008;358(26):2765-2775.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

83

160. Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term 

enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a 

double-blind, randomised controlled trial. Lancet. Jul 5 2008;372(9632):31-39.

161. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis 

after total knee arthroplasty. The New England journal of medicine. Jun 26 2008;358(26):2776-

2786.

162. Turpie AG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for 

thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. May 16 

2009;373(9676):1673-1680.

163. Patel VP, Walsh M, Sehgal B, Preston C, Dewal H, Di Cesare PE. Factors associated with 

prolonged wound drainage after primary total hip and knee arthroplasty. Journal of Bone and 

Joint Surgery-American Volume. Jan 2007;89A(1):33-38.

164. Asensio A, Antolin FJ, Sanchez-Garcia JM, et al. Timing of DVT prophylaxis and risk of 

postoperative knee prosthesis infection. Orthopedics. Nov 2010;33(11):800.

165. 3973 Bozic KJ, Vail TP, Pekow PS, Maselli JH, Lindenauer PK, Auerbach AD. Does aspirin have a 

role in venous thromboembolism prophylaxis in total knee arthroplasty patients? Journal of 

Arthroplasty. Oct 2010;25(7):1053-1060.

166. Sachs RA, Smith JH, Kuney M, Paxton L. Does anticoagulation do more harm than good? A 

comparison of patients treated without prophylaxis and patients treated with low-dose warfarin 

after total knee arthroplasty. Journal of Arthroplasty. Jun 2003;18(4):389-395.

167. Parvizi J, Ghanem E, Joshi A, Sharkey PF, Hozack WJ, Rothman RH. Does "excessive" 

anticoagulation predispose to periprosthetic infection? Journal of Arthroplasty. Sep 

2007;22(6):24-28.

168. Miner AL, Losina E, Katz JN, Fossel AH, Platt R. Deep infection after total knee replacement: 

impact of laminar airflow systems and body exhaust suits in the modern operating room. Infect 

Cont Hosp Ep. Feb 2007;28(2):222-226.

169. Hooper GJ, Rothwell AG, Frampton C, Wyatt MC. Does the use of laminar flow and space suits 

reduce early deep infection after total hip and knee replacement? The ten-year results of the 

New Zealand Joint Registry. Journal of Bone and Joint Surgery-British Volume. Jan 

2011;93B(1):85-90.

170. Pasquarella C, Pitzurra O, Herren T, Poletti L, Savino A. Lack of influence of body exhaust gowns 

on aerobic bacterial surface counts in a mixed-ventilation operating theatre. A study of 62 hip 

arthroplasties. The Journal of hospital infection. May 2003;54(1):2-9.

171. Chiu FY, Chen CM, Lin CF, Lo WH. Cefuroxime-impregnated cement in primary total knee 

arthroplasty: a prospective, randomized study of three hundred and forty knees. The Journal of 

bone and joint surgery. American volume. May 2002;84-A(5):759-762.

172. Chiu FY, Lin CF, Chen CM, Lo WH, Chaung TY. Cefuroxime-impregnated cement at primary total 

knee arthroplasty in diabetes mellitus. A prospective, randomised study. The Journal of bone 

and joint surgery. British volume. Jul 2001;83(5):691-695.

173. Mu Y, Edwards JR, Horan TC, Berrios-Torres SI, Fridkin SK. Improving risk-adjusted measures of 

surgical site infection for the national healthcare safety network. Infection control and hospital 

epidemiology : the official journal of the Society of Hospital Epidemiologists of America. Oct 

2011;32(10):970-986.

174. Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant pathogens associated with 

healthcare-associated infections: summary of data reported to the National Healthcare Safety 

Network at the Centers for Disease Control and Prevention, 2009-2010. Infection control and 
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

84

hospital epidemiology : the official journal of the Society of Hospital Epidemiologists of America. 

Jan 2013;34(1):1-14.

175. Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG. CDC definitions of nosocomial surgical 

site infections, 1992: a modification of CDC definitions of surgical wound infections. Infection 

control and hospital epidemiology : the official journal of the Society of Hospital Epidemiologists 

of America. Oct 1992;13(10):606-608.

176. Urban JA. Cost analysis of surgical site infections. Surgical infections. 2006;7 Suppl 1:S19-22.

177. Fry DE. The economic costs of surgical site infection. Surgical infections. 2002;3 Suppl 1:S37-43.

178. Yasunaga H, Ide H, Imamura T, Ohe K. Accuracy of economic studies on surgical site infection. 

The Journal of hospital infection. Feb 2007;65(2):102-107.

179. Umscheid CA, Mitchell MD, Doshi JA, Agarwal R, Williams K, Brennan PJ. Estimating the 

proportion of healthcare-associated infections that are reasonably preventable and the related 

mortality and costs. Infection control and hospital epidemiology : the official journal of the 

Society of Hospital Epidemiologists of America. Feb 2011;32(2):101-114.

180. Bozic KJ, Ries MD. The impact of infection after total hip arthroplasty on hospital and surgeon 

resource utilization. The Journal of bone and joint surgery. American volume. Aug 

2005;87(8):1746-1751.

181. Kurtz SM, Lau E, Watson H, Schmier JK, Parvizi J. Economic burden of periprosthetic joint 

infection in the United States. The Journal of arthroplasty. Sep 2012;27(8 Suppl):61-65 e61.

182. Engemann JJ, Carmeli Y, Cosgrove SE, et al. Adverse clinical and economic outcomes attributable 

to methicillin resistance among patients with Staphylococcus aureus surgical site infection. 

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 

Mar 1 2003;36(5):592-598.

183. Bratzler DW, Houck PM, Surgical Infection Prevention Guidelines Writers W, et al. Antimicrobial 

prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention 

Project. Clinical infectious diseases : an official publication of the Infectious Diseases Society of 

America. Jun 15 2004;38(12):1706-1715.

184. Bratzler DW, Hunt DR. The surgical infection prevention and surgical care improvement projects: 

national initiatives to improve outcomes for patients having surgery. Clinical infectious diseases : 

an official publication of the Infectious Diseases Society of America. Aug 1 2006;43(3):322-330.

185. Malpiedi PJ, Peterson KD, Soe MM, et al. 2011 National and state healthcare-associated 

infection standardized infection ratio report. Published February 11, 2013. Available at: 

http://www.cdc.gov/hai/national-annual-sir/index.html. Accessed June 26, 2013.

186. Agency for Healthcare Research and Quality. Healthcare Cost and Utilization Project net 

(H•CUPnet). 2011 Nationwide Inpatient Sample (NIS). 2011; Available at: 

http://hcupnet.ahrq.gov/HCUPnet.jsp?Id=C3BCA3A3EAC235A4&Form=SelALLLISTED&JS=Y&Acti

on=%3E%3ENext%3E%3E&_ALLLISTED=Yes. Accessed June 26, 2013.

187. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee 

arthroplasty in the United States from 2005 to 2030. The Journal of bone and joint surgery. 

American volume. Apr 2007;89(4):780-785.

188. Kurtz SM, Lau E, Schmier J, Ong KL, Zhao K, Parvizi J. Infection burden for hip and knee 

arthroplasty in the United States. The Journal of arthroplasty. Oct 2008;23(7):984-991.

189. Kurtz SM, Ong KL, Schmier J, Zhao K, Mowat F, Lau E. Primary and revision arthroplasty surgery 

caseloads in the United States from 1990 to 2004. The Journal of arthroplasty. Feb 

2009;24(2):195-203.

190. Bozic KJ, Kurtz SM, Lau E, et al. The epidemiology of revision total knee arthroplasty in the 

United States. Clinical orthopaedics and related research. Jan 2010;468(1):45-51.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

85

191. Kurtz SM, Ong KL, Schmier J, et al. Future clinical and economic impact of revision total hip and 

knee arthroplasty. The Journal of bone and joint surgery. American volume. Oct 2007;89 Suppl 

3:144-151.

192. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. The New England journal of 

medicine. Oct 14 2004;351(16):1645-1654.

193. Donlan RM. New approaches for the characterization of prosthetic joint biofilms. Clinical 

orthopaedics and related research. Aug 2005(437):12-19.

194. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. 

Clinical microbiology reviews. Apr 2002;15(2):167-193.

195. Wolcott RD, Rhoads DD, Bennett ME, et al. Chronic wounds and the medical biofilm paradigm. 

Journal of wound care. Feb 2010;19(2):45-46, 48-50, 52-43.

196. Berbari EF, Marculescu C, Sia I, et al. Culture-negative prosthetic joint infection. Clinical 

infectious diseases : an official publication of the Infectious Diseases Society of America. Nov 1 

2007;45(9):1113-1119.

197. Trampuz A, Piper KE, Jacobson MJ, et al. Sonication of removed hip and knee prostheses for 

diagnosis of infection. The New England journal of medicine. Aug 16 2007;357(7):654-663.

198. Malekzadeh D, Osmon DR, Lahr BD, Hanssen AD, Berbari EF. Prior use of antimicrobial therapy is 

a risk factor for culture-negative prosthetic joint infection. Clinical orthopaedics and related 

research. Aug 2010;468(8):2039-2045.

199. American Academy of Orthopaedic Surgeons. Guidelines. Diagnosis of periprosthetic infection of 

the hip and knee. 2010; Available at: http://www.aaos.org/research/guidelines/PJIguideline.asp. 

Accessed June 28, 2013.

200. Bedair H, Ting N, Jacovides C, et al. The Mark Coventry Award. Diagnosis of early postoperative 

TKA infection using synovial fluid analysis. Clinical orthopaedics and related research. Jan 

2011;469(1):34-40.

201. Bori G, Munoz-Mahamud E, Garcia S, et al. Interface membrane is the best sample for 

histological study to diagnose prosthetic joint infection. Modern Pathol. Apr 2011;24(4):579-

584.

202. Morgan PM, Sharkey P, Ghanem E, et al. The value of intraoperative gram stain in revision total 

knee arthroplasty. Journal of Bone and Joint Surgery-American Volume. Sep 2009;91A(9):2124-

2129.

203. Bottner F, Wegner A, Winkelmann W, Becker K, Erren M, Gotze C. Interleukin-6, procalcitonin 

and TNF-alpha: markers of peri-prosthetic infection following total joint replacement. The 

Journal of bone and joint surgery. British volume. Jan 2007;89(1):94-99.

204. Buttaro MA, Tanoira I, Comba F, Piccaluga F. Combining C-reactive protein and interleukin-6 

may be useful to detect periprosthetic hip infection. Clinical orthopaedics and related research. 

Dec 2010;468(12):3263-3267.

205. Di Cesare PE, Chang E, Preston CF, Liu CJ. Serum interleukin-6 as a marker of periprosthetic 

infection following total hip and knee arthroplasty. The Journal of bone and joint surgery. 

American volume. Sep 2005;87(9):1921-1927.

206. Drago L, Vassena C, Dozio E, et al. Procalcitonin, C-reactive protein, interleukin-6, and soluble 

intercellular adhesion molecule-1 as markers of postoperative orthopaedic joint prosthesis 

infections. Int J Immunopath Ph. Apr-Jun 2011;24(2):433-440.

207. Worthington T, Dunlop D, Casey A, Lambert P, Luscombe J, Elliott T. Serum procalcitonin, 

interleukin-6, soluble intercellular adhesin molecule-1 and IgG to short-chain exocellular 

lipoteichoic acid as predictors of infection in total joint prosthesis revision. Brit J Biomed Sci. 

2010;67(2):71-76.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

86

208. Nilsdotter-Augustinsson A, Briheim G, Herder A, Ljunghusen O, Wahlstrom O, Ohman L. 

Inflammatory response in 85 patients with loosened hip prostheses - A prospective study 

comparing inflammatory markers in patients with aseptic and septic prosthetic loosening. Acta 

Orthopaedica. 2007;78(5):629-639.

209. Holinka J, Bauer L, Hirschl AM, Graninger W, Windhager R, Presterl E. Sonication cultures of 

explanted components as an add-on test to routinely conducted microbiological diagnostics 

improve pathogen detection. J Orthop Res. Apr 2011;29(4):617-622.

210. Nguyen LL, Nelson CL, Saccente M, Smeltzer MS, Wassell DL, McLaren SG. Detecting bacterial 

colonization of implanted orthopaedic devices by ultrasonication. Clinical orthopaedics and 

related research. Oct 2002(403):29-37.

211. Sorli L, Puig L, Torres-Claramunt R, et al. The relationship between microbiology results in the 

second of a two-stage exchange procedure using cement spacers and the outcome after revision 

total joint replacement for infection. The use of sonication to aid bacteriological analysis. Journal 

of Bone and Joint Surgery-British Volume. Feb 2012;94B(2):249-253.

212. Vergidis P, Greenwood-Quaintance KE, Sanchez-Sotelo J, et al. Implant sonication for the 

diagnosis of prosthetic elbow infection. J Shoulder Elb Surg. Dec 2011;20(8):1275-1281.

213. Koskela A, Nilsdotter-Augustinsson A, Persson L, Soderquist B. Prevalence of the ica operon and 

insertion sequence IS256 among Staphylococcus epidermidis prosthetic joint infection isolates. 

Eur J Clin Microbiol. Jun 2009;28(6):655-660.

214. Arciola CR, Campoccia D, Baldassarri L, et al. Detection of biofilm formation in Staphylococcus 

epidermidis from implant infections. Comparison of a PCR-method that recognizes the presence 

of ica genes with two classic phenotypic methods. Journal of biomedical materials research. Part 

A. Feb 2006;76(2):425-430.

215. Holmberg A, Lood R, Morgelin M, et al. Biofilm formation by Propionibacterium acnes is a 

characteristic of invasive isolates. Clinical Microbiology and Infection: the Official Publication of 

the European Society of Clinical Microbiology and Inf. Aug 2009;15(8):787-795.

216. Neut D, van Horn JR, van Kooten TG, van der Mei HC, Busscher HJ. Detection of biomaterialassociated infections in orthopaedic joint implants. Clinical orthopaedics and related research. 

Aug 2003(413):261-268.

217. Stoodley P, Kathju S, Hu FZ, et al. Molecular and imaging techniques for bacterial biofilms in 

joint arthroplasty infections. Clinical orthopaedics and related research. Aug 2005(437):31-40.

218. Dubouix-Bourandy A, de Ladoucette A, Pietri V, et al. Direct detection of Staphylococcus 

osteoarticular infections by use of Xpert MRSA/SA SSTI real-time PCR. J Clin Microbiol. Dec 

2011;49(12):4225-4230.

219. Kobayashi N, Inaba Y, Choe H, et al. Simultaneous intraoperative detection of methicillinresistant Staphylococcus and pan-bacterial infection during revision surgery. Use of simple DNA 

release by ultrasonication and real-time polymerase chain reaction. Journal of Bone and Joint 

Surgery-American Volume. Dec 2009;91A(12):2896-2902.

220. Krimmer V, Merkert H, von Eiff C, et al. Detection of Staphylococcus aureus and Staphylococcus 

epidermidis in clinical samples by 16S rRNA-directed in situ hybridization. J Clin Microbiol. Aug 

1999;37(8):2667-2673.

221. Montanaro L, Arciola CR, Baldassarri L, Borsetti E. Presence and expression of collagen adhesin 

gene (cna) and slime production in Staphylococcus aureus strains from orthopaedic prosthesis 

infections. Biomaterials. Oct 1999;20(20):1945-1949.

222. Riggio MP, Dempsey KE, Lennon A, Allan D, Ramage G, Bagg J. Molecular detection of 

transcriptionally active bacteria from failed prosthetic hip joints removed during revision 

arthroplasty. Eur J Clin Microbiol. Jul 2010;29(7):823-834.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

87

223. Rohde H, Burandt EC, Siemssen N, et al. Polysaccharide intercellular adhesin or protein factors in 

biofilm accumulation of Staphylococcus epidermidis and Staphylococcus aureus isolated from 

prosthetic hip and knee joint infections. Biomaterials. Mar 2007;28(9):1711-1720.

224. Larsen LH, Lange J, Xu Y, Schonheyder HC. Optimizing culture methods for diagnosis of 

prosthetic joint infections: a summary of modifications and improvements reported since 1995. 

Journal of medical microbiology. Mar 2012;61(Pt 3):309-316.

225. Workgroup Convened by the Musculoskeletal Infection S. New definition for periprosthetic joint 

infection. The Journal of arthroplasty. Dec 2011;26(8):1136-1138.

226. McGinn T, Wyer PC, Newman TB, et al. Tips for learners of evidence-based medicine: 3. 

Measures of observer variability (kappa statistic). CMAJ : Canadian Medical Association journal = 

journal de l'Association medicale canadienne. Nov 23 2004;171(11):1369-1373.

227. Whitlock EP, Lin JS, Chou R, Shekelle P, Robinson KA. Using existing systematic reviews in 

complex systematic reviews. Annals of internal medicine. May 20 2008;148(10):776-782.

228. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of 

prophylactic antibiotics in labor and delivery. Obstetrics and gynecology. Jun 2011;117(6):1472-

1483.

229. Anonymous. Antimicrobial prophylaxis for surgery. Treatment guidelines from the Medical 

Letter. Oct 2012;10(122):73-78; quiz 79-80.

230. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial 

prophylaxis in surgery. American Journal of Health-System Pharmacy: AJHP: the Official Journal 

of the American Society of Health-System Pharmacists. Feb 1 2013;70(3):195-283.

231. Engelman R, Shahian D, Shemin R, et al. The Society of Thoracic Surgeons practice guideline 

series: Antibiotic prophylaxis in cardiac surgery, part II: Antibiotic choice. The Annals of thoracic 

surgery. Apr 2007;83(4):1569-1576.

232. van Schalkwyk J, Van Eyk N, Society of Obstetricians Gynaecologists of Canada Infectious 

Diseases Committee. Antibiotic prophylaxis in obstetric procedures. Journal of Obstetrics and 

Gynaecology Canada: JOGC = Journal d'Obstetrique et Gynecologie du Canada: JOGC. Sep 

2010;32(9):878-892.

233. Bauer LA, Edwards WA, Dellinger EP, Simonowitz DA. Influence of weight on aminoglycoside 

pharmacokinetics in normal weight and morbidly obese patients. European journal of clinical 

pharmacology. 1983;24(5):643-647.

234. National Institute for Health and Clinical Excellence (NICE). Surgical Site Infection: Prevention 

and Treatment of Surgical Site Infection (NICE Clinical Guideline 74). 2008; 

http://www.nice.org.uk/cg74fullguideline. Accessed July 29, 2013.

235. Arnoczky SP, Shebani-Rad S. The Basic Science of Platelet-rich Plasma (PRP): What Clinicians 

Need to Know. Sports medicine and arthroscopy review. Dec 2013;21(4):180-185.

236. Marlovits S, Mousavi M, Gabler C, Erdos J, Vecsei V. A new simplified technique for producing 

platelet-rich plasma: a short technical note. European spine journal : official publication of the 

European Spine Society, the European Spinal Deformity Society, and the European Section of the 

Cervical Spine Research Society. Oct 2004;13 Suppl 1:S102-106.

237. Hsu WK, Mishra A, Rodeo SR, et al. Platelet-rich plasma in orthopaedic applications: evidencebased recommendations for treatment. The Journal of the American Academy of Orthopaedic 

Surgeons. Dec 2013;21(12):739-748.

238. Martinez-Zapata MJ, Marti-Carvajal AJ, Sola I, et al. Autologous platelet-rich plasma for treating 

chronic wounds. Cochrane Database Syst Rev. 2012;10:CD006899.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

88

239. Bielecki TM, Gazdzik TS, Arendt J, Szczepanski T, Krol W, Wielkoszynski T. Antibacterial effect of 

autologous platelet gel enriched with growth factors and other active substances: an in vitro 

study. The Journal of bone and joint surgery. British volume. Mar 2007;89(3):417-420.

240. Moojen DJ, Everts PA, Schure RM, et al. Antimicrobial activity of platelet-leukocyte gel against 

Staphylococcus aureus. J Orthop Res. Mar 2008;26(3):404-410.

241. O'Grady NP, Alexander M, Burns LA, et al. Guidelines for the prevention of intravascular 

catheter-related infections. American journal of infection control. May 2011;39(4 Suppl 1):S1-34.

242. Wilson AP, Treasure T, Sturridge MF, Gruneberg RN. A scoring method (ASEPSIS) for 

postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet. Feb 8 

1986;1(8476):311-313.

243. Dumville JC, Walter CJ, Sharp CA, Page T. Dressings for the prevention of surgical site infection. 

The Cochrane database of systematic reviews. 2011(7):CD003091.

244. Lazar HL, McDonnell M, Chipkin SR, et al. The Society of Thoracic Surgeons practice guideline 

series: Blood glucose management during adult cardiac surgery. The Annals of thoracic surgery. 

Feb 2009;87(2):663-669.

245. Umpierrez GE, Hellman R, Korytkowski MT, et al. Management of hyperglycemia in hospitalized 

patients in non-critical care setting: an endocrine society clinical practice guideline. The Journal 

of clinical endocrinology and metabolism. Jan 2012;97(1):16-38.

246. Jacobi J, Bircher N, Krinsley J, et al. Guidelines for the use of an insulin infusion for the 

management of hyperglycemia in critically ill patients. Critical care medicine. Dec 

2012;40(12):3251-3276.

247. Qaseem A, Humphrey LL, Chou R, Snow V, Shekelle P, Physicians CGCotACo. Use of intensive 

insulin therapy for the management of glycemic control in hospitalized patients: a clinical 

practice guideline from the American College of Physicians. Annals of internal medicine. Feb 15 

2011;154(4):260-267.

248. National Institute for Clincial Excellence (NICE). Management of inadvertent perioperative 

hypothermia in adults (NICE Clinical Guideline 65). 2008; 

http://www.nice.org.uk/Guidance/CG65. Accessed June 29, 2013.

249. Forbes SS, Eskicioglu C, Nathens AB, et al. Evidence-based guidelines for prevention of 

perioperative hypothermia. Journal of the American College of Surgeons. Oct 2009;209(4):492-

503 e491.

250. Hooper VD, Chard R, Clifford T, et al. ASPAN's evidence-based clinical practice guideline for the 

promotion of perioperative normothermia: second edition. Journal of Perianesthesia Nursing: 

Official Journal of the American Society of PeriAnesthesia Nurses / Ameri. Dec 2010;25(6):346-

365.

251. Meyhoff CS, Jorgensen LN, Wetterslev J, Christensen KB, Rasmussen LS, Group PT. Increased 

long-term mortality after a high perioperative inspiratory oxygen fraction during abdominal 

surgery: follow-up of a randomized clinical trial. Anesthesia and analgesia. Oct 2012;115(4):849-

854.

252. Bailey IS, Karran SE, Toyn K, Brough P, Ranaboldo C, Karran SJ. Community surveillance of 

complications after hernia surgery. Bmj. Feb 22 1992;304(6825):469-471.

253. Carson JL, Grossman BJ, Kleinman S, et al. Red blood cell transfusion: a clinical practice guideline 

from the AABB*. Annals of internal medicine. Jul 3 2012;157(1):49-58.

254. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology 

recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in 

the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). May 2012;64(5):625-639.
DISCLAIMER: This document is a DRAFT. The findings and conclusions in this draft guideline have not been formally disseminated by the 

Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. 

89

255. Visser K, Katchamart W, Loza E, et al. Multinational evidence-based recommendations for the 

use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating 

systematic literature research and expert opinion of a broad international panel of 

rheumatologists in the 3E Initiative. Ann Rheum Dis. Jul 2009;68(7):1086-1093.

256. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations 

for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid 

arthritis. Arthritis Rheum. Jun 15 2008;59(6):762-784.

257. Ledingham J, Deighton C, British Society for Rheumatology Standards, Guidelines and Audit 

Working Group. Update on the British Society for Rheumatology guidelines for prescribing 

TNFalpha blockers in adults with rheumatoid arthritis (update of previous guidelines of April 

2001). Rheumatology. Feb 2005;44(2):157-163.

258. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 

recommendations for the use of nonpharmacologic and pharmacologic therapies in

osteoarthritis of the hand, hip, and knee. Arthritis Care & Research (Hoboken). Apr 

2012;64(4):465-474.

259. Centers for Disease Control and Prevention. Healthcare Infection Control Practices Advisory 

Committee. Siegel JD, Rhinehart E, Jackson M, Chiarello L, and the Healthcare Infection Control 

Practices Advisory Committee. 2007 Guideline for isolation precautions: preventing transmission 

of infectious agents in healthcare settings 2007; Available at: 

http://www.cdc.gov/ncidod/dhqp/pdf/isolation2007.pdf. Accessed August 5, 2013.

260. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: 

Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest 

Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e278S325S.

261. Jacobs JJ, Mont MA, Bozic KJ, et al. American Academy of Orthopaedic Surgeons clinical practice 

guideline on: preventing venous thromboembolic disease in patients undergoing elective hip 

and knee arthroplasty. Journal of Bone & Joint Surgery. American Volume. Apr 18 

2012;94(8):746-747.