Incidence and Microbial Profiles of Periprosthetic Joint Infection After Total Knee Arthroplasty in Obese vs Non-Obese Patients
Conditions: Knee Arthropathy, PJI
Sponsor: Bispebjerg Hospital

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Incidence and Microbial Profiles of Periprosthetic Joint Infection After 
Total Knee Arthroplasty in Obese vs Non-Obese Patients: Protocol and 
Statistical Analysis Plan for a Nationwide Register-Based Study 
 
Authors 
Saber M. Aljuboori, MD, PhD Fellow1,2,4; Espen Solem, MD, PhD, Associate Professor3,4; Henrik 
Calum, MD, PhD6; Robin Christensen, MSc, PhD, Professor2,5; Søren Overgaard, MD, DMSci, 
Professor1,4 
 
1. Department of Orthopaedic Surgery and Traumatology, Copenhagen University Hospital, Bispebjerg and 
Frederiksberg, Copenhagen, Denmark; 2. Section for Biostatistics and Evidence-Based Research, the Parker Institute, 
Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark; 3. Copenhagen Phase IV unit 
(Phase4CPH), Department of Clinical Pharmacology and Center of Clinical Research and Prevention at Copenhagen 
University Hospital, Bispebjerg and Frederiksberg; 4. University of Copenhagen, Department of Clinical Medicine, 
Faculty of Health and Medical Sciences; 5. Research Unit of Rheumatology, Department of Clinical Research, 
University of Southern Denmark, Odense University Hospital, Denmark; 6. Department of Clinical Microbiology, 
Hvidovre Hospital, Copenhagen University Hospital, Copenhagen, Denmark 
 
 

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SUMMARY 
Importance: After a primary total knee arthroplasty (TKA), we anticipate that obese individuals 
are more likely to experience a of periprosthetic joint infection (PJI). Knowing the microbial profile 
in obese patients can potentially help in choosing the proper prophylactic measures for this group 
as well as tailoring the empirical antibiotics in relation to PJI in obese patients. 
Objective: To compare incidence of PJI revisions within 2 years after TKA in obese vs non-obese 
OA patients. Secondarily: To compare microbial profiles of infections in these groups in two time 
windows: early (≤90 days) vs late (91–730 days) and incidence of revisions due to all causes within 
2 years.Design and Setting: We will include patients having primary knee arthroplasty using 
Danish national registers. Patients will be stratified into anthropometric groups, referred to as 
exposed and unexposed to obesity, based on their baseline Body Mass Index (BMI). Participants 
included in the analysis population will be followed up for 2 years, until first revision, death or 
migration whichever comes first. 
Participants: We will include adult patients with available weight and height data with 
primary/idiopathic or secondary (due to meniscus or cruciate ligament lesion) OA who received 
primary TKA in the period from 2011-01-01 and 2021-02-28. Patients will be identified from the 
Danish knee arthroplasty register. 
Exposure and Comparator: The cohort will be divided into obese (exposed), defined as body 
mass index (BMI) ≥ 30 kg/m2; and non-obese (unexposed), defined as BMI < 30 kg/m2. 
Main Outcomes and Measures: The primary outcome will be revision due to prosthetic joint 
infection (PJI) within 730 days following TKA. Secondary endpoints will then be to examine 
revision due to all causes within 730 days following TKA and type of microbial infection between 
obese and non-obese in the first 90 days and the period from 91 days to 730 days following TKA. 
Planned Statistical Analyses: We will use descriptive statistics to summarize the baseline 
characteristics of the two groups. Hazard ratios with corresponding two-sided 95% confidence 
intervals (95%CIs) for experiencing the outcome will be estimated using a Cox proportional 
hazards regression model. We will fit both unadjusted (crude) model and a propensity score 
adjusted model calculated based on age, sex, highest completed education, household income, 
comedications, and Elixhauser Comorbidity Measure (ECM), all collected up to the day of surgery. 
Stratified analyses will categorize PJI cases by bacterial infection and compare crude proportions 
between groups based on the absolute risk difference with 95% confidence intervals. 
Ethical Considerations and Registration: The study and its statistical analysis plan will be 
registered in clinicaltrials.org prior to conducting the study. 
 

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INTRODUCTION 
Knee arthroplasty are effective treatments of end-stage joint disease not responding to other treatment 
measures.1 Periprosthetic Joint infection (PJI) is an unusual but devastating complication of joint 
arthroplasty.2–4 It carries significant burden on patients’ morbidity in terms of severe pain, deceased 
physical activity and quality of life and may lead to death.5–7 The microbial profile of PJI significantly 
influences treatment outcomes, with Gram-negative bacteria (GNB), including multidrug-resistant (MDR) 
pathogens having highest rate of failures,8 coagulase negative staphylococcus was also found to 
experience a high risk of re-revision.9 Studies have linked increasing body mass index (BMI), smoking, male 
gender, diabetes, rheumatoid arthritis, depression, history of steroid use and previous joint surgery with an 
increased risk of PJI after Total Knee Arthroplasty (TKA); from these, increasing BMI is found to be the 
most consistent risk factor for developing PJI.10–13  
Theories to understand and by that prevent PJI in overweight and obese patients have been 
proposed; under-dosed prophylactic antibiotics, increased surface tension, increased blood glucose and 
increased bacterial colonization of the skin in the groin are possible explanations of the association 
between PJI and overweight. A previous study showed that obese patients have higher rates of 
polymicrobial and Gram-negative early periprosthetic joint infections of the hip than non-obese patients.14 
This study looked however only in early infections treated with debridement, antibiotics and implant 
retention (DAIR). A single previous cohort study from England and Wales found that the mean BMI was 
higher in Mixed genus PJI.15 We anticipate that knowing the microbial profile in obese patients can help in 
choosing the proper prophylactic measures for this group as well as tailoring the empirical antibiotics in 
relation to PJI in obese patients. 
 
Objectives 
The primary objective is to compare the incidence of periprosthetic joint infection (PJI) within 2 years of 
surgery between obese and non-obese patients undergoing primary total knee arthroplasty (TKA) for knee 
osteoarthritis. Subsequently examine the microbial profiles associated with PJI in these groups withing the 
first 90 days and in the period from 91 days to 2 years following surgery. Finally we will compare the 
incidence of revision due to all causes within 2 years of surgery between obese and non-obese patients 
undergoing primary total knee arthroplasty. 
 
Study design 
The study is designed as a nationwide, register-based study investigating the influence of obesity on the 
microbial profile of PJI after TKA. The study will follow the REporting of studies Conducted using 
Observational Routinely-collected Data (RECORD) guidelines.16 We will be comparing the microbial profile 
of obese patients with BMI of 30 kg/m2 (exposed) with non-obese (unexposed) patients, defined as BMI < 
30 kg/m2.17 
 
Setting 
All Danish residents have a personal identification number consistent throughout all registers making 
register-linkage possible. We will include patients with PJI diagnosis after their primary hip or knee 

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arthroplasty using Danish national registers. Patients will be followed up for 2 years, until first revision, 
death or migration whichever comes first. 
 
Data sources 
The Danish Civil Registration System (DCRS) contains information on the CPR number, vital and migrant 
status, cohabiting status, and municipality of residence.18 The Danish Knee Arthroplasty Register (DKR) is 
nation-wide register that contains information on all primary knee arthroplasty procedures and revisions 
performed in Denmark, e.g., baseline characteristics as age, sex, BMI, at the time of TKA operation. The 
registry started in 1997 and the reporting to the registry became mandatory since 2006. DKR is known for 
high degree of coverage and completeness.19,20 The Danish Microbiology Database (MiBa) is a national 
database containing data from all samples received by the Danish clinical microbiology departments from 
both hospitals and general practices with complete coverage since 2010.21 
The Danish National Patient Register (DNPR) is a valuable tool for epidemiological research, 
providing longitudinal registration of diagnoses, treatments, and examinations derived from every 
hospital contact in Denmark with complete nationwide coverage since 1978.22 The Danish National 
Prescription Registry has kept information on all prescriptions for drugs dispensed by community 
pharmacies in Denmark since 1994 according to Anatomical Therapeutic Chemical (ATC) classification 
system (ATC codes). Data from the Danish National Prescription Registry does not include hospital 
dispensaries.23 
The Danish Registers on Personal Income and Transfer Payments contains more than 160 
variables including salaries, entrepreneurial income, taxes, public transfer payments, capital income, 
private pension contributions, and pay-outs. In addition, Statistics Denmark provide more detailed 
registers on specific income transfers, including sickness benefit, old age pension, disability pension, and 
cash and unemployment benefits.24 The Danish Population Education Register provides information on 
education status on Danish population, and it carries high degree of validity and coverage.25  
 
Study population 
In order to be eligible, we will include adult patients with primary or secondary osteoarthritis (due to 
meniscus or cruciate ligament lesion) who underwent primary TKA between January 1, 2011, and February 
28, 2021, and for whom weight and height data are available. Patients will be identified from the DKR. 
Patients are followed for 2 years, until first revision, death or migration, whichever comes first. 
 
Variables 
Outcomes and endpoints 
1. The primary outcome is revision due to prosthetic joint infection (PJI) within 2 years following TKA 
2. The first secondary outcome is types of microbial profiles detected in the PJIs, short term (≤90 
days) and long-term (91 days to 2 years) 
3. Another secondary outcome is revision due to all causes within 2 years following TKA. 
 

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For the revision due to PJI, we will stratify the outcome looking into the proportions of the following 
groups of bacteria within the first 90 days and between 91 and 730 days following TKA: 
A. PJI due to Staphylococcus aureus. 
B. PJI due to Coagulase-negative staphylococci. 
C. PJI due to other gram-positive bacteria. 
D. PJI due to gram-negative bacteria. 
E. PJI due to anaerobic bacteria. 
F. PJI due to mycoplasmic infection. 
G. PJI due to polymicrobial infection. 
H. PJI with negative culture.  
 
Definitions 
PJI: our definition of PJI is adapted from The European Bone and Joint Infection Society (EBJIS) criteria26 as 
at least one of the following: 
A. DKR-registered revision surgery due to infection. 
B. At least 2 deep-tissue samples of phenotypically indistinguishable bacteria 
isolated from at least 3 deep-tissue samples  
C. One or more positive intraoperative samples from a closed fluid aspirate AND a 
biopsy (fluid AND tissue) of phenotypically indistinguishable bacteria isolated.  
 
Covariates 
The cohort will be divided into two groups at baseline: obese, defined as BMI ≥30 kg/m², and non-obese, 
defined as BMI <30 kg/m².For descriptive purposes and adjusting, we will be using the following pre-TKA 
exposure covariates: age (years) at the time of TKA, sex (coded as female=1; male = 0), household income 
(at the year before KA, categorized into quartiles), highest completed education (at the year of KA, 
categorized into 3 categories: <11, 11 to 15, and >15 years). Comedication (at least one redeemed 
prescription 365 days earlier to index KA - 60 days for antibiotics): 1) Glucose-lowering due to the 
association between DM and surgical complications.27,28 2) Antithrombotic medications and 3) NSAIDs 
because of the possible postoperative bleeding-related complications29 and 4) Antiresorptives due to the 
possible increased risk of revision.30 The last covariate to be included in matching and adjustment is 
Elixhauser Comorbidity Measure (ECM) (at the year of KA, categorized into 3: 0, 1-2 and ≥ 3), ECM is 
validated comorbidity scoring measure that has shown highest discriminative ability for the occurrence of 
all categories of postoperative adverse outcomes following orthopedic surgeries.31–33 
 
Statistical Methods 

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We will use descriptive statistics to summarize baseline characteristics of the two groups and will compare 
them using standardized differences. . The 2-year (730 days) cumulative incidence of PJI will be reported 
for both groups. Hazard ratios with corresponding two-sided 95% confidence intervals (CIs) will be 
estimated using a Cox proportional hazards regression model. We will fit both unadjusted (crude) models 
and propensity adjusted models using inverse probability of treatment weighting (IPTW).34 For the 
adjusted model, propensity scores will be calculated based on age in years, female sex, completed 
education, household income, comedications, and ECM (all collected prior to surgery). Subsequent 
stratified analyses will categorize the observed PJI cases by bacterial infection type (within the first 90 days 
postoperatively or between 91 days and 2 years) and compare crude proportions between groups based on 
the absolute risk difference with 95% confidence intervals. 
We present several analyses corresponding to the main results with 95% confidence intervals rather than P 
values, and comply with 2 Acta Orthopaedica principles for concluding whether scientifically important 
differences exist 35: 
• 
A statistically non-significant test is not sufficient to claim “no difference.” To show “no difference,” 
a smallest clinically relevant size of the difference (it might be 0) must be defined. If all clinically 
relevant differences are excluded from the difference’s confidence interval, a “no difference” or 
similarity/comparability conclusion is reasonable.  
• 
A statistically significant test does not necessarily imply a clinically important difference. The 
importance of the tested null hypothesis depends on the smallest clinically relevant difference that 
should be defined a priori. If the difference’s confidence interval excludes all clinically irrelevant 
differences, a conclusion concerning the existence of a clinically important difference is 
reasonable. 
To evaluate imprecision in the estimated treatment effect, a clinically important difference must first be 
defined. Based on an expected 2-year incidence of PJI of about 1%,36 a 50% increase in risk would be 
considered clinically relevant. In a time-to-event analysis, this corresponds to a hazard ratio of 1.5. 
Accordingly, non-inferiority—or absence of a clinically meaningful increase in risk—will be established if 
the upper bound of the 95% confidence interval for the hazard ratio remains below 1.5. We will visualize 
the 2-year cumulative incidence of all outcomes for both groups using the cumulative incidence functions 
(CIFs). 
Handling of missing data and sensitivity analyses: Missing data is unavoidable in epidemiological and 
clinical research and must be explained otherwise it could undermine the credibility and validity of the 
research results. Missing values, for either predictors or outcomes, occur in all types of medical research. 
Unless prompted to do otherwise, most statistical packages explicitly exclude individuals with any missing 
value on any of the data analyzed. The resulting so-called “available case” or “complete case” analysis is 
the most common “default approach” to handle missing data, although it is rarely justified. 35 Subjects with 
missing weight or height will be excluded from the analysis. Missingness of data on some of the covariates 
used for adjusting will be ignored but the subjects will not be excluded. Patients who will be lost during the 
follow up period (e.g., due to death or migration) are expected to be extremely few and no systematic 
difference is expected to be seen.  
Therefore, this missingness of outcome data will be assumed “Missing completely at 
random” (MCAR), as there is no evidence to suggest systematic differences between the missing values 
and the observed values and will be ignored. For the purpose of sensitivity, we will potentially re-do the 
main analysis where missing outcome data is replaced twice, using best-case imputation (y=0; no PJI) and 
worst-case imputation (y=1, PJI yes). 

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Figure 1 (Mockup): study flow chart 
 
 
 

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Table 1 (Mockup). Baseline characteristics at time of total knee arthroplasty 
  
Obese 
Non-Obese 
Std. Diff 
Age, years 
Female Sex, no. (%) 
BMI, kg/m2 
Highest completed Education: 
      <11 years, no. (%) 
      11 to 15 years, no. (%) 
       >15 years, no. (%) 
Household income: 
      Lowest (1st quantile), no. (%) 
      Low (2nd qunatile), no. (%) 
      Medium (3rd quantile), no. (%) 
      High (4th quantile), no. (%) 
Comedications: 
      Antithrombotics, no. (%) 
      Antibiotics, no. (%) 
      Glucose-Lowering, no. (%) 
      NSAIDs, no. (%) 
      Antiresorptives, no. (%) 
ECM 
 
 
 
      0, no. (%) 
      1 to 2, no. (%) 
      ≥ 3, no. (%) 
Abbreviations: BMI: body mass index; NSAIDs: Non-Steroidal anti-inflammatory drugs; ECM: 
Elixhauser Comorbidity measure; Std. Diff: Standardized Difference. 
 
 

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Figure 2 (Mockup): Simulated data illustrating the cumulative incidence of A) Prosthetic joint infection 
(PJI); B) all-cause revision. 
A
  B
 
 
Table 2 (Mockup): Incidence for Periprosthetic joint infection (PJI) and all cause revision at 2 years 
in obese and non-obese patients with an unadjusted and adjusted analyses of the Hazard Ratios 
(HR) between the 2 groups over the full 2-year period 
  
Obese 
Non-Obese 
HR [95% CI*] 
Crude analyses: 
 
 
 
N 
xx 
xx 
 
PJI, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
All cause revision, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
Adjusted analyses: 
 
 
 
N 
xx 
xx 
 
PJI, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
All cause revision, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
*CI: Confidence Interval 
 
 
 
 
 
 
 

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Table 3 (Mockup): Microbial profiles in revisions for prosthetic joint infection (PJI) within the first 90 
days and between 90 days and 2 years postoperatively. 
  
Obese Non-Obese 
Absolute Risk 
Difference [95% CI*] 
N 
xx 
xx 
PJI, 90 days, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Staphylococcus aureus, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Coagulase-negative staphylococci, no. 
(%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Other gram-positive, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Gram-negative, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Anaerobes, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Fungal, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Mycoplasma, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  polymicrobial, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Culture-negative, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
 
 
 
 
PJ, 91 days - 2 years, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Staphylococcus aureus, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Coagulase-negative staphylococci, no. 
(%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Other gram-positive, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Gram-negative, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Anaerobes, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Fungal, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Mycoplasma, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  polymicrobial, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Culture-negative, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
*The 95% confidence intervals (CI) will not be adjusted for multiplicity and should not be used in place of hypothesis 
testing. 
 
 
 
 

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Sensitivity analyses  
A sensitivity analysis will also be done to report PJI-likely revisions and the microbial profiles in these 
patients. PJI-likely revisions will be defined as revisions surgeries with at least one of the following: A) One 
single intraoperatively obtained positive culture obtained from the revision surgery (aspiration fluid OR 
tissue biopsy) regardless of the microorganism. B) One single positive culture obtained from aspiration of 
synovial fluid regardless of microorganism. If we do not find a difference between obese and non-obese, 
we will run a sensitivity analysis where we compare morbidly obese patients (BMI ≥ 40 kg/m2) with other 
patients (BMI<40 kg/m2). If the primary analysis showed a difference between obese and non-obese, a 
sensitivity analysis comparing morbidly obese (BMI≥40 kg/m2) with non-morbidly obese (BMI 30-40 kg/m2) 
will be done. 
 
Sensitivity analysis table 1: Incidence for Periprosthetic joint infection-likely (PJI) revision at 2 years 
in obese and non-obese patients with the relative risk (RR) and an unadjusted and adjusted analyses 
of the Hazard Ratios (HR) between the 2 groups 
  
Obese 
Non-Obese 
HR [95% CI*] 
Crude analyses: 
 
 
 
N 
xx 
xx 
 
PJI-likely, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
Adjusted analyses: 
 
 
 
N 
xx 
xx 
 
PJI-likely, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
*CI: Confidence Interval 
 
 
 
 
 
 
 

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Sensitivity analysis table 2: Prosthetic joint infection-likely (PJI-likely) within the first 90 days 
and in 91 days-2 years postoperatively stratified by the type of infection 
  
Obese 
Non-Obese 
Absolute Risk 
difference [95% CI*] 
N 
xx 
xx 
PJI-likely, 90 days, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Staphylococcus aureus, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Coagulase-negative staphylococci, no. (%) xx (xx) 
xx (xx) 
xx [xx to xx] 
  Other gram-positive, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Gram-negative, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Anaerobes, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Fungal, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Mycoplasma, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Multibacterial, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
 
 
 
 
PJI-likely, 91 days - 2 years, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Staphylococcus aureus, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Coagulase-negative staphylococci, no. (%) xx (xx) 
xx (xx) 
xx [xx to xx] 
  Other gram-positive, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Gram-negative, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Anaerobes, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Fungal, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Mycoplasma, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Multibacterial, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
*The 95% confidence intervals (CI) will not be adjusted for multiplicity and should not be used in place of hypothesis 
testing. 
  
 

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Sensitivity analysis table 3: Incidence for Periprosthetic joint infection (PJI) and all cause revision 
at 2 years in morbidly obese and non-morbid patients with an unadjusted and adjusted analyses 
of the Hazard Ratios (HR) between the 2 groups 
  
Morbidly-Obese 
Non-morbid 
HR [95% CI*] 
Crude analyses: 
 
 
 
N 
xx 
xx 
 
PJI, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
Revision due to all causes, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
Adjusted analyses: 
 
 
 
N 
xx 
xx 
 
PJI, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
Revision due to all causes, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
*CI: Confidence Interval 
 
 
 
 
 
 
Sensitivity analysis table 4: Prosthetic joint infection in morbidly-obese within the first 90 days and  
in 91 days-2 years postoperatively stratified by the type of infection 
  
Morbidly-obese Non-morbid 
Absolute Risk 
difference [95% CI*] 
N 
xx 
xx 
PJI, 90 days, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Staphylococcus aureus, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Coagulase-negative staphylococci, no. (%) xx (xx) 
xx (xx) 
xx [xx to xx] 
  Other gram-positive, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Gram-negative, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Anaerobes, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Fungal, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Mycoplasma, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Multibacterial, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
 
 
 
 
PJI, 91 days - 2 years, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Staphylococcus aureus, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Coagulase-negative staphylococci, no. (%) xx (xx) 
xx (xx) 
xx [xx to xx] 
  Other gram-positive, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Gram-negative, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Anaerobes, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Fungal, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Mycoplasma, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
  Multibacterial, no. (%) 
xx (xx) 
xx (xx) 
xx [xx to xx] 
*The 95% confidence intervals (CI) will not be adjusted for multiplicity and should not be used in place of hypothesis testing. 
 
 
 

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HEALTH RESEARCH ETHICS AND GENERAL CONSIDERATIONS  
Funding 
Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg 
Hospital is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL). Saber M. Saber is 
supported by a grant from Karen Elise Jensens Fond. The supporting institutions had no role in study 
design or writing of this protocol. 
 
Conflict of interest 
All will be disclosed. 
 
Disclaimers 
The views expressed in the submitted protocol are the authors’ own and not an official position of the 
institution or funder. 
 
Ethics 
In Denmark, the Act on Processing of Personal Data does not require ethical permission or obtained 
consent for anonymised retrospective register studies. The Danish Data Protection Agency has approved 
the study with nr p-2023-14433. 
 
 

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References: 
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2. 
Kurtz SM, Ong KL, Lau E, Bozic KJ, Berry D, Parvizi J. Prosthetic Joint Infection Risk after TKA in the Medicare 
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