### A PUBLIC HEALTH ACTION PLAN TO COMBAT ANTIMICROBIAL **RESISTANCE 2012 Update** 
**Interagency Task Force on Antimicrobial Resistance**

**Co -**  **Chairs: Centers for Disease Control and Prevention**  **Food and Drug Administration National Institutes of Health**  **Participa ting Agencies:**  **Agency for Healthcare Research and Quality Centers for Medicare and Medicaid Services**  **Department of Agriculture Department of Defense**  **Department of Veterans Affairs Environmental Protection Agency**  **Health Resources and Services Administration Health and Human Services/** **Office of the As sistant Secretary for Health**  **Health and Human Services/ Office of the Assistant Secretary for Preparedness and Response** - 1
- 

### Preface This 2012 update of the 2011 revision of the A Public Health Acti on Plan to Combat Antimicrobial Resistance , provides a listing of projects that the Federal Agencies in the Interagency

Task Force on Antimicrobial Resistance are pursuing or planning to pursue in an effort to respond to the complex and pressing topic of a ntimicrobial resistance. The past decade has seen extraordinary

change in the microbiology an d epidemiology of antimicrobial
- resistant microbes and subsequent changes in treatment and patient outcomes. The Task Force is taking further s trides to ensure that the Action Plan remains current and relevant as the agencies continue to look towards the future b y taking the following steps:

 Actions, the numbered items that follow each goal, will be reviewed biennial ly by the Task Force beginning in 2013. New ac tions will be added as needed and existing actions may be modified or deleted in response to progress or changes that occur in the future with regard to antimicrobial resistance . This will allow the Action Plan to be updated over time and will help all Ta sk Force agencies to continue to collaborate most effectivel y in achieving Action Plan goals.  Implementation steps or p rojects, the lettered items that follow action items, are being revised annually . In this first annual update, n ew projects have been added, and some existing projects have been modified in response to intervening events. Completed projects have been moved to an Appendix , and their outcomes will be cross
- referenced to the yearl y progress report for the ye ar during which the project was completed. For example, projects completed in 2011 are listed in Appendix A: Retired Projects and Implementation Steps . The outcomes of these projects can be found in the 2011 Progress Towards Implementation of: A Public Health Action Plan To Combat Antimi crobial Resistance
. The Task Force and all participating Federal agencies continue to stress the importance of good communication with the many stakeholders who share the Task Force’s goals of preventing and controlling antimicrobial resistant infections . The Task Force remains committed to continuing communication with the public and health professionals, since antimicrobial resistance so profoundly

affects public health and clinical medicine. Among these efforts is the 2012 annual public meeting of th e Task Force, scheduled for November 15 . Given the public health consequences of AR and its ever
- changing nature, the Task Force will continue to address the issue of antimicrobial resistance in this and future versions of the Action Plan.- 2
-



### A **Public Health Action Plan t o Combat Antimicrobial Resistance**  **Table of Contents** Executive Summary
................................ ................................ ................................ ........................ 3 Introduction and Overview
................................ ................................ ................................ ......... 5 The Focus Areas
................................ ................................ ................................ ........................... 13 Focus Area I: Surveillance
................................ ................................ ................................ ........ 13 Focus Area II: Pre vention and Control
................................ ................................ ..................... 22 Focus Area III: Research
................................ ................................ ................................ .......... 29 Focus Area IV: Product Development
................................ ................................ ...................... 32 Acron ym s and Abbreviations
................................ ................................ ................................ ....... 35 Appendix A: Retired Projects and Implementation Steps
................................ ............................ 36- 3
-



### A Public Health **Action Plan to Combat Antimicrobial Resistance**

**Executive Summary** The Interagency

Task Force on Antimicrobial Resistance (hereafter referred to as the Task Force) was created in 1999 to coordinate the activities of federal agencies in addressing antimicro bial a resistance (AR) in recognition of the increasing importance of AR as a public health threat. The Task Force is co
- chaired b y the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and the National Institutes of Health (NIH) and also includes the Agency for Healthcare Research and Quality (AHRQ), the Centers for Medicare and Medicaid Services (CMS), the Department of Agriculture (USDA), the Department of Defense (DoD), the Department of Veterans Affairs (VA), the Environmental Protection Agency

(EPA), the Health Resources and Serv ices Administration (HRSA), the Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response (HHS/ASPR), and the Office of the As sistant Secretary for Health (HH S/OASH). In 2001, the Task Force developed an initial Action Plan, outlining specific issues, goals, and actions important for addressing the problem of AR. This document, entitled A Public Health Action Plan to Combat Antimicrobial Resistance, Part I : Domestic Issues , reflected a broad
based consensus of participating federal agencies, which was reached with individual input from state and local health agencies, universities, professional societies, pharmaceutical companies, healthcare del ivery

organizations, agricultural producers, consumer groups, and other members of the public. Continued collaboration with these partners has been vital to achieving successful implementation of the Action Plan. In 2011, the Action P lan was revised based in part on individual input obtained at a consultants’ meeting held in Atlanta, Georgia in December 2007. Present at the public meeting were consu ltants with wide
- ranging expertise in areas such as human and veterinary medicine, pharmaceutical and diagnos tics manufacturing, animal husbandry , clinical microbiology , epidemiology , and infectious disease s and infection control, and state and local public health officials
. This 2012 update reflects changes since the 2011 Action Plan. The Action Plan include s action items organized into four focus areas: Surveillance, Prevention and Control, Research, and Product Development. Within each of these four areas, specific goals are listed. The focus areas and goals are as follows: I. Surveillance  Goal 1: Improve the detection, monitoring, and characterization of drug
- resistant infections in humans and animals.

a In this document, the term “antimicrobial” is used inclusively to refer to any agent (including an antibiotic) used to kill or inhibit the growth of microorganisms (bacteria, viruses, fungi, or parasites). This term generally a pplies to agents intended for healthcare, veterinary, and agricultural applications.- 4
-

 Goal 2: Better define, characterize, and measure the impact of antimicrobial drug use in humans and animals in the United States. II. Prevention and Control  Goal 3: Develop, implement, and evaluate strategies to prevent the emergence, transmission, and persistence of drug
- resistant microorganisms.  Goal 4 : Develop, implement, and evaluate strategies to improve appropriate antimicrobial use. III. Research  Goal 5: Facilitate basic research on antimicrobial resistance.  Goal 6: Facilitate the translation of basic research findings into practical applications for the prevention, diagnosis , and treatment of resistant infections.  Goal 7: Facilitate clinical research to improve the treatment and prevention of antimicrobial drug resistant infections.  Goal 8: Conduct and support epidemiological studies to identify key drivers of the emergence and spread of AR in various populations. IV . Product Development  Goal 9: P rovide information on the status of antibacterial drug product development and clari f y recommended clinical trial designs for antibacterial products
.  Goal 10: Consider opportunities for international harmonization and means to update susceptibility

testing information for human and animal use.  Goal 11: Encourage development of rapid diagnostic test s and vaccines. The Task Force will continue to facilitate coordination among agencies and monitor implementation of the plan. As has been done since 2001, the Task Force will continue to publish annual reports detailing how the plan is being implemented, solicit comments from the public, and update the plan.- 5 - 

### Introduction and Overview Background In the 1940s, the widespread availability of penicillin and the subsequent discovery of streptomycin led to a dramatic reduction in illness and death from infectious diseases. However, bacteria and other disease
- causing organisms

— viruses, fungi, and parasites

— have a remarkable ability

to mutate and acquire resis tance genes from other organisms and thereby develop resistance to antimicrobial drugs. When an antimicrobial drug is used, the selective pressure exerted b y the drug favors the growth of organisms that are resistant to the drug's action. The extensive use of antimicrobial drugs has resulted in drug resistance that threatens to reverse the m edical advances of the last seventy ye ars . Drug - resistant pathogens are a growing menace to all people, regardless of age, gender, or socioeconomic background. They en danger people in affluent, industrial societies like the United States, as well as in less
- developed nations. Examples of clinicall y important microbes that are rapidly developing resistance to available antimicrobials include bacteria that cause pneumonia , ear infections, and meningitis (e. g., Streptococcus pneumoniae ), skin, bone, lung, and bloodstream infections (e. g., Staphylococcus aureus ), urinary tract infe ctions (e.g., Escherichia coli ), foodborne infections (e.g., Salmonella or E. coli acquired fro m meat, eggs, nuts, fresh produce etc
. ), and infections transmitted in healthcare settings (e.g., enterococci, Acinetobacter baumanii, Pseudomonas aeruginosa , and Klebsiella spp. ). Antimicrobial resistance (AR) is not a new phenomenon; however, the current magnitude of the problem and the speed with which new resistance phenoty pes have emerged elevates the public health significance of this issue. In addition, the declining number of new antimicrobial agents limits treatment options, particularly for patie nts with infections caused b y multidrug
- resistant organisms. For example, surveillance data for S. pneumoniae , a common cause of bacterial respiratory

tract infections, showed that 24 percent of isolates were no t susceptib le to penicillin. In addition, res istance to several other antibacterial drugs is common ; 1.5 percent of isolates we re resistant to cefotaxime (a "third
- generation" cephalosporin antibiotic), and resistance to the newer fluoroquinolone antimicrobials has already been reported. b Nearl y all strains of Staphylococcus aureus in the United States are resistant to penicillin, and many are resistant to new er methicillin
- related drugs
. V ancom ycin for many years has been the only

uniforml y effective treatment against these methicillin
- resistant strains, but over the last decade there have been reported strains of S. aureus with decreased susceptibility and isolates resistant to vancom ycin
. The public health burden of methicillin
- resistant Staphylococcus aureus (MRSA) is staggering , with over 90,000 i nvasive MRSA infections per year estimated in the U.S. population. c

b Active Bacterial Core Surveillance (ABCs) Report Emerging Infections Program Network Streptococcus pneumoniae , 2008 available at: http://www.cdc.gov/abcs/reports
- findings/survreports/spneu08.pdf c Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators. Invasive methicillin
- resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763
- 71.- 6
-

Many other pathogens

– including the bacteria that cause tuberculosis and gonorrhea , human immunodeficiency

virus (HIV) , the fungi that cause yeast infections , and the parasites that caus e malaria

– are also becoming resistant to current therapies. For instance, CDC modified its treatment recommendations for gonorrhea in 2007 due to increasing and widespread fluoroquinolone resistance in Neisseria gonorrhoeae
. d Since 2007, the emergence of N. gonorrhoeae with increasing MICs of cephalosporins has the potential to m ake some cases of disease untreatable. e The unpredictable and fluid nature of AR is also illustrated by the prevalence of resistant Acinetobacter baumannii among military personn el in and returning from conflict areas and in hospital outbreaks in civilian U.S. hospitals. f Drug choices for the treatment of other infections are becoming incr e asingl y limited and expensive, and, in some cases, nonexistent. Since their discovery , ant imicrobials have been used extensively in livestock and poultry

for the treatment, control, and/or prevention of animal diseases, as well as for production purposes (e.g., to enhance growth, improve feed efficiency). In contrast to human medicine where tre atment is customarily

directed at the patient, entire groups of animals may be treated by

the use of medicated feed and/or water. As a result of continued exposure to antimicrobials, the prevalence of resistant bacteria in the fecal flora of food animals c an be relativel y high. T he impact of increases in resistant bacteria in food animals o n the management of human infections is an ongoing concern as many classes of antimicrobials used in food
- producing animals have analogues to human therapeutics and are therefore capable of selecting for similar resistance phenoty pes. Risk Drug - resistant infections may be acquired in healthcare settings (e.g., gram - negative infections in intensive care units), in the community (e.g., pneumococci acquired from a classmate ), and through the food supply

(e.g., salmonella acquired from meat or eggs), both domestically and around the world
. While anyone may acquire a drug
- resistant infection, certain people are at increased risk, e.g., patients in hospitals and children in daycare centers. However, resistant

d Update to CDC’s Sexually Transmitted Disease s Treatment Guidelines, 2006: Fluoroquinolones No Longer Recommended for Treatment of Gonococcal Infections. MMWR 56(14);332
- 336. April 13, 2007. e Bolan GA, Sparling PF, Wasserheit JN. The emerging threat of untreatable gonococcal infection. N Engl J Med
. 2012 Feb 9;366(6):485
- 7. f Scott P, Deye G, Srinivasan A, Murray C, Moran K, Hulten E, Fishbain J, Craft D, Riddell S, Lindler L, Mancuso J, Milstrey E, Bautista CT, Patel J, Ewell A, Hamilton T, Gaddy C, Tenney M, Christopher G, Petersen K, Endy T, Petr uccelli B.An outbreak of multidrug
- resistant Acinetobacter baumannii
- calcoaceticus complex infection in the U.S. military health care system associated with military operations in Iraq. Clin Infect Dis. 2007 Jun 15;44(12):1577
- 84. Epub 2007 May 8. Jones A, Morgan D, Walsh A, Turton J, Livermore D, Pitt T, Green A, Gill M, Mortiboy D. Importation of multidrug
- resistant Acinetobacter spp infections with casualties from Iraq. Lancet Infect Dis. 2006 Jun;6(6):317
- 8. Moran KA, McAllister CK, Gray PJ Multidrug
- resistant Acinetobacter extremity infections in soldiers. Davis KA,. Emerg Infect Dis. 2005 Aug;11(8):1218
- 24. Munoz - Price LS, Weinstein RA. Acinetobacter infection. N Engl J Med. 2008 Mar 20;358(12):1271
- 81.- 7 -

microbes are increasingly appearing in new settings. MRSA , which for 30 years was almost exclusively a problem in hospitals, is now oc curring in the community among otherwise healthy persons . g Costs The costs of treating AR infections place a significant burden on society — a burden that is likely to grow larger as the number of cases of drug
- resistant illness increase s . Individuals infected with drug
- resistant organisms are more li kely to remain in the hospital f or a long er time, and to have poor er prognose s . h In a 2008 study of antimicrobial resistant infections acquired in the hospital, the medical costs attributable to the infection ranged from $18,588 to $29,069 per patient, hospital stay s were extended between 6.4 to 12.7 day s, and the attributable mortality of the resistant infection was 6.5%. Using the most conservative estimates, the total cost of resistant infections in the 188 patients from this study was $13.35 million dollars. These findings suggest that signifi cant health and economic benefits are possible through efforts to reduce antimicrobial resistance and healthcare
- associated infections. Solutions AR will alway s be with us. The challenge before us is to transform this increasingl y urgent threat into a manageable problem. In the past , the Institute of Medicine , the American Society for M icrobiology , the World Health Organization (WHO) , the Congressional Offi ce of Technology Assessment, the G overnment Accountability Office , the Infectious Disease Society of America, and other panels of distinguished experts have provided recommendations and options for government action to address the dangers posed b y AR. Inaddition, a 2009 U.S.
- EU Summit Declaration included a statement to establish a transatlantic task fo rce on AR. i The experts agree that we need to improve surveillance for emerging AR problems, to prolong the useful life of antimicrobial drugs, to develop new drugs , and to utilize other measures ( e.g., improved vaccines, diagnostics, and infection control interventions ) to prevent and control AR. The problem is urgent , the achievement of these goals has not been simple or straightforward, and accomplishments to date , while notable, have been insufficient. Monitoring, preventing, and controlling AR requires sustained effort, commitment, and collaboration among many groups in the public and private sectors, and involvement of the general public. It also requires continuing support and leadership from F ederal and state government s and a willingness to addres s complex and sometimes controversial scientific, medical, and economic issues. Focus Areas

g Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators. Invasive methicillin
- resistant Staphylococcus aureus infec tions in the United States. JAMA. 2007 Oct 17;298(15):1763
- 71. h Roberts, RR, Hota B, Ahmad I, Scott RD II, Foster SD, Abbasi F, Schabowski S, Kampe LM, Ciavarella GG, Supino M, Naples J, Cordell R, Levy SB, Weinstein, RA. Hospital and societal costs of antimicrobial
- resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin. Infect. Dis. 2009; 49:1175
- 84. i http://www. whitehouse.gov/the
- press - office/us
- eu - joint
- declaration
- and
- annexes- 8
-

The Action Plan includes action items organized into four focus areas: Surveillance, Prevention and Control, Research, and Product Development. Each focus area co ntains specific action items, projects and implementation steps. In addition to these, a selection of AR activities, in which the Task Force is actively

engaging, is highlighted below. j I. Surveillance Unless AR problems are detected as they emerge and a ctions are taken quickly to contain them, the world may

soon be faced with previousl y treatable diseases that have again become untreatable, as in the pre
- antibiotic era. Early detection of new and emerging resistance, ongoing monitoring of resistant infec tions, and information on antimicrobial use will allow experts to quickly interpret trends and identify strategies to prevent or mitigate the development and spread of AR
. The Action Plan incorporates several action items aimed at strengthening, expanding , and coordinating existing national and international surveil lance s ys tems for antimicrobial
- resistant microorganisms. Additional action items in this area focus on addressing barriers to timel y dissemination and updating of surveillance data and gatherin g information on antimicrobial use practices
. Over the next few ye ars, CDC wi ll address several action items in this focus area b y continuing to expand and improve its surveillance s ys tems that collect data on AR. For instance, the National Healthcare Sa fety Network (NHSN) is a surveillance s ys tem that provides healthcare facilities a way

to track, anal yz e, and interpret data on healthcare
- associated infections ( HAIs ), including those caused by antimicrobial
- resistant pathogens. NHSN is expanding to impro ve its capacity for collection and anal ys is of data on multidrug
- resistant organisms (MDROs) and antimicrobial drug use. In addition to monitoring resistance in healthcare settings, CDC is maintain ing surveillance activities for pathogens affecting the gen eral population through efforts such as the Emerging Infections Program (EIP), a population
- based network of CDC and state health departments, National Antimicrobial Resistance Monitoring Sy stem (NARMS) , the Gonococcal Isolate Surveillance Project , and the National Tuberculosis Surveillance S ys tem. Through the EIP program, CDC closely monitors invasive bacterial pathogens through Active Bacterial Core surveillance . In partnership, FDA, USDA , and CDC track resistance amo ng enteric pathogens through NARMS
. O n - farm pilot projects were initiated in 2011 to test the feasibility of expanding NARMS to include a preharvest component to the sampling design. In addition to monitoring resistance among bacterial pathogens, CDC continue s to monitor resistance among no n - bacterial pathogens such as influenza, malaria , and HIV , both domestically and internationall y. II. Prevention and Control

j These highlighted activities are provided as illustrative examples and do not represent a comprehensive list.- 9
-

The prevention and control of antimicrobial
- resistant infections requires measures to prevent the transmission of resistant micro organisms and promote the appropriate use k of antimicrobial agents. While development of new antimicrobial agents and effective stewardship of existing agents are cornerstones of activities to protect the health of the nation in the face of expanding AR , successful prevention of resistance occurs by reducing the size of the populations of resistant microorganisms in humans, animals, and the environment
. Preventing infections with resistant strains of a microorganism can also be accomplished b y preventing or eliminating all infections caused b y that microorganism. F or example , drug
resistant malaria is rampant in parts of the world, but malaria was effectively eliminated from the United States through mosquito control efforts . Antibiotic resistance in Haemophilus influenzae was the threat that dictated antibiotic choice for virtually all invasive bacterial infections in yo ung children in the United States as recently as 15 years ago, but following the introduction of Haemophilus infuenzae seroty pe b ( HIB ) vaccines this problem has nearl y been eliminated. A ction items in this area address extending the useful life of antimicrobial drugs b y encouraging appropriate use through educational efforts such as the Get Smart: Know When Antibiotics W ork campaigns , p reventing infection transmission through improved infection control methods and use of vaccines, and preventing and controlling emerging AR problems in agriculture, human , and veterinary

medicine. AR prevention and control activities that will be key over the next few years include several interagency

collaborations focused on controlling and preventing MRSA infections l within healthcare settings. Based upon the successful prevention initiative involving the VA Pittsburgh Healthcare S ys tem and CDC demonstrating a reduction of MRSA infections, that initiative was expanded into an additional 17 sites within the Vetera ns Health Administration (VHA). The VHA ’s MRSA Prevention Initiative is now a nationwide effort to reduce healthcare
- associated MRSA infection in hospital patients . VHA is also evaluating lessons learned from the MRSA Prevention Initiative to explore initiatives directed at other MDROs as well as Clostridium difficile
. Also continuing over the next few years is an interagency initiative to identify

and help suppress the spread of MRSA and other related infections through an ongoing partnership between CDC and AHRQ. The two agencies are working together to identify gaps in the prevention, diagnosis, and treatment of MRSA and related infections a cross the healthcare s ys tem and to fund research, implementation, measurement, and evaluation pra ctices that mitigate healthcare
- related infections.

k In this Action Plan , appropriate antimicrobial drug use is defined as use that maximizes therapeutic impact while minimizing toxicity and the development of resistance. In pr actice, this means prescribing antimicrobial therapy when and only when beneficial to a patient; targeting therapy to the desired pathogens; and using the appropriate agent , dose, and duration. l Jain, R., S.M. Kralovic, et al. (2011). “Veterans Affairs I nitiative to Prevent Methicillin
- Resistant Staphylococcus aureus Infections.” New

England Journal of Medicine **364** (15): 1419
- 1430.- 10
-

Several Task Force member agencies, including AHRQ, CDC, FDA, NIH, CMS , and VA are working to implement the HHS Action Plan to Prevent Health Care
- Associated Infections (HAI) m , which includes reduction targets for both Clostridium difficile and MRSA. By working to implement the HHS HAI Action Plan these agencies and partners will impact several areas and acti on i tems covered in this 2012 AR Action Plan. III. Research Understanding the fundamental processes involved in AR within microbes and the resulting impact on humans, animals, and the environment forms an important basis for influencing and changing thes e processes and outcomes. Basi c and clinical research provide the fundamental knowledge necessary

to develop appropriate responses to the emergence and spread of AR in hospitals, communities, farms, and the food supply . Critical activities in this focus ar ea include support of basic research to uncover new targets and new antimicrobials, investigations into the development of resistance and host
- pathogen interactions, optimiz ation of treatment for resistant pathogens, and translati on of research findings into clinically useful products, such as novel approaches to detect, prevent, and treat antimicrobial
- resistant infections. NIH continues to engage in AR research activities that address multiple action items in this focus area. In addition to an extensive investigator
- initiated grants portfolio, NIH support s the basic research activities of the Genomic Sequencing Centers for Infectious Diseases and the Bioinformatics Resource Centers for Infectious Diseases. The objective of the sequencing centers is to pro vide rapid and cost
- efficient production of high
- quality genome sequences of microorganisms and invertebrate vectors of infectious diseases and to make the resulting genomic data rapidly

and readil y accessible to the broader scientific community through pu

blicly accessible international databases. In addition, the sequencing centers provide comparative genomics and genotyping services to examine genetic variation in populations and communities of human pathogens and also across the human genome to identify genetic associations with observable phenoty

pes in the pathogen and in the human host
. T he bioinformatics resource centers provide the scientific community free access to resources for the query , anal ys is , and display o f such information through user
- frien dl y interfaces. NIH currentl y supports clinical trials aimed at identifying way s to reduce the use of licensed antibacterials in both community and healthcare settings
. These trials focus on areas of greatest antimicrobial drug exposure, such as pneum onia , otitis media , skin and soft tissue infection , and bacteremia, and emplo y s trategies to reduce use, such as shorter courses of antimicrobial treatment ; using antimicrobials only where indicated; different dosages/frequencies to achieve desirable in vi vo efficacy; validation of the key components of multi
- drug therap y; and optimal use of off
- patent antimicrobials to prev ent the emergence of resistance. IV . Product Development

m The HHS Action Plan t o Prevent Healthcare
- Associated Infections is available on the HHS website at: http://www.hhs.gov/ophs/initiatives/hai/infection.html- 11
-

There is a critical need for new drugs, vaccines, and diagnostic tests to treat, prevent, and diagnose infections, including serious and life
- threat ening infections caused by drug
- resistant bacteria. FDA is working on a study to better understand the trends over time in the development of new antibacterial drugs, the number of drugs approved, and reasons why development programs may

not have achieved approval. The Action Plan incorporates action items that will facilitate the development of vaccines and diagnostic tests for pathogens for which AR poses a significant problem for treatment or public health. FDA is working on a number of guidances on approaches to evaluating new antimicrobial products. Providing guidance can help b y identifying recommended scientific approaches and also to identify

areas where additional developmental work would be beneficial for the design and conduct of studies. Over the last few years, FDA has held several public workshops and/or Advisory Committee meetings to discuss clinical trial designs for evaluating antibacterial drugs. FDA has also publis hed several guidance documents that describe recommended approaches regarding clinical trial designs. n One particular example of the efforts to date is the work to refine clinical trial designs for studying antibacterial drugs for the treatment of hospital
- acquired bacterial pneumonia (HA B P) and ventilat or - associated bacterial pneumonia (VABP). As part of these efforts, in 2009, FDA co - sponsored a public workshop with the Infectious Diseases Society of America, the American College of Chest Ph ys icians, the Society of Critical Care Medicine, and the American Thoracic Society regarding scientific issues in clinical trial design for HA B P and VABP. This public workshop provide d information about and gain ed perspective from health care providers, academi cs , and industry

on various aspects of antimicrobial drug development for HA B P and VAB P, including diagnosis, treatment, trial endpoints, and statistical issues in analy sis of res ults of trials in HABP and VABP. In the next few years, FDA will engage in activiti es to address a number of the action items in the Product Development focus area. FDA will be working to provide clarity on recommended approaches for evaluating new medical products for bacterial disease through publishing guidance documents. FDA plans t o publish guidance documents on recommended clinical trial designs for evaluating antibacterial drugs for conditions such as acute bacterial skin and skin structure infections and hospital
- acquired and ventilator
- associated bacterial pneumonia. In additio n, FDA also plans to publish guidance for establishing performance for in vitro diagnostics assay s for MRSA and vancom ycin
- resistant enterococci (VRE). These guidances will describe recommended approaches for developing new antimicrobial products for speci fic uses.

n Examples of recent guidance documents: Antibacterial Drug Products: Use of Noninferiority Studies to Support Approval (draft, October 2007), Acute Bacteri al Sinusitis: Developing Antimicrobial Drugs for Treatment (draft, October 2007), Acute Bacterial Otitis Media: Developing Drugs for Treatment (draft, January 2008), Acute Bacterial Exacerbations of Chronic Bronchitis in Patients with Chronic Obstructive P ulmonary Disease: Developing Antimicrobial Drugs for Treatment (draft, August 2008), Community
- Acquired Bacterial Pneumonia: Developing Drugs for Treatment (draft, March 2009), Non
- Inferiority Clinical Trials (draft, March 2010)- 12
-

The Biomedical Advanced Research Development Authority (BARDA), in the HHS Office of the Assistant Secretary

for Preparedness and Response o is designing and implementing programs that create partnerships between government and industry based on support and incentives that induce commercial enterprises to address public health and biodefense priorities. BARDA is currentl y supporting the development of an intravenous formulation of a next
generation aminogl ycoside antibiotic for the treatment of p lague and tularemia, as well as ventilator
- associated pneumonia. In2012, BARDA established an additional partnership for the development of a next generation tetracycline antibiotic for the treatment of anthrax, plague, and tularemia, as well as community- acquired bacterial pneumonia. BARDA is projecting an expansion of this program in the near
- term by supporting the development of more novel antimicrobial candidates for the treatment and prevention of diseases caused by bacterial threat agents as well a s diseases caused by clinic ally prevalent infectious disea ses, including those that are antimicrobial resistant
.

o See http://www.phe.gov/about/barda/Pages/default.aspx for more information on BARDA- 13
- 

### The Focus Areas Following each of the goals listed for each focus area are several action items that define topi c areas for specific projects or implementation steps (numbered items). Wherever possible, action items are populated with specific projects or implementation steps (lettered items) to provide greater specificity

for planned federal activities. The action items, projects, and implementation steps do not represent an exhaustive list of activities. p The expected completion dates for specific projects and implementation steps are indicated with a date. For example, (2012 ) means that the work is expected to be completed by the end of the 2012 calendar year. Some activities are ongoing an d are indicated as such. P roject lists will be updated annuall y, and actions will be updated every

two years. 

### Focus Area I: Surveillance **Overarching goals** In order to develo p and implement effective control strategies there must be 1) continuous or periodic monitoring of infections caused b y AR microorganisms and 2) comprehensive knowledge of the use of antimicrobial agents across all sectors. Goal 1: Improve the detection, monitoring, and characterization of drug
- resistant infections in humans and animals. 1.1 Develop strategies to more accuratel y assess the burden of antimicrobial drug resistance in the community through the enhancement of existing sy stems including the Emergi ng In fections Program ( EIP ) and the Epidemiology and L aboratory

Capacity (ELC) sites
. a) Completed: See Appendix A. b) Facilitate surveillance for resistant enteric bacteria by construction of a web interface for data entry and reporting results between state and federal participants in the National Antimicrobial Resistance Monitoring Sy stem (NARMS) (2012). c) Implement electronic tools to query resistance prevalence among enteric pathogens collected in NARMS (2015). d) Report regular summaries of antimicrobial re sistance trends and mechanisms among foodborne bacterial pathogens on the NARMS website and in the literature (ongoing). e) Expand the Gonococcal Isolate Surveillance Project (GISP) to include a s tate public health laboratory

for sentinel site reference susc eptibility testing (2011) and initiate CDC
- p Because of the rapidly evolving nature of AR, there will likely be new or emerging challenges in antimicrobial resistance subseque nt to the publication of this Action Plan. The Task Force is committed to identifying and responding to these issues as they arise.- 14
-

administered external quality assessment testing to ensure accurate testing at all 5 sentinel sites (2012). f) Expand GI SP to include surveillance to identify the emergence of cephalosporin
- resistant Neisseria gonorrheae by

monitoring for gonorrhea cephalosporin treatment failures (2011). Data anal ys is and report will be completed in 2014. g) NEW: The U
. S
. Army's Multidrug
- resistant organism Repository and Surveillance Network (MRSN) at the Walter Reed Arm y Institute o f Research in Silver Spring, MD will enhance efforts to extend its surveillance network to monitor the DoD beneficiary community

worldwide (ongoing). h) NEW: Conduct and report results of susceptibility testing of representative bacterial isolates from enteric disease outbreaks (ongoing). i) NEW: L ink data in NARMS to data in other enteric disease surveillance s ystems to better understand and characterize the burden of resistant enteric infections and to identify risk factors for acquiring these infections (ong oing). j) NEW: Determine food, water, and other sources for resistant versus susceptible enteric infections (ongoing). k) NEW: I dentify

sources of resistant enteric infections among travelers returning to the United States (ongoing). l) NEW: Determine the preval ence of antimicrobial resistance among enteric organisms of livestock on farms (ongoing)
. Coordinator: CDC; Collaborators: FDA, USDA, VA , DoD 1.2 Develop strategies to more accuratel y assess the burden of antimic robial resistance in healthcare settings throu gh the enhancement of existing sy stems including NHSN, the EIP, and EL C sites
. a) Expand NHSN to use electronicall y- captured antimicrobial susceptibility data from participating facilities for reporting of resistance rates and trends; pilot expansion plan in 2011
- 2012 , provide results of pilot in 2012, develop a web
- based query for users in 2014 , and provide ongoing periodic reports o f the collected resistance data. b) Report regular summaries to provide national estimates of the resistance burden using data reported on HAI s to NHSN (ongoing). c) Evaluate the utility

of electronic rules for identifying and reporting central line
- associated bloodstream infections, surgical site infections (2011), catheter
- related urinary tract infections (2012), and ventilator
- asso ciated pneumonia (201 2 ), including associated- 15
-

pathogens; and compare electronic algorithms with traditional manual surveillance by infection control professionals (CLABSIs 2011). d) Develop a s ys tem to collect representative sets of bacterial isolates to ass ess changes in resistance mechanisms or strains nationally and work with the Clinical and Laboratory Standards Institute (CL SI) to determine the impact of changes on antimicrobial susceptibility

testing and reporting practices in the United States. e) Colle ct convenience samples of bacterial and fungal isolates through the EIP to assess changes in antimicrobial
- resistant pathogens such as MRSA ( ongoing ), Clostridium difficile ( ongoing ), and selected gram
- negative bacteria ( ongoing ), as well as community
asso ciated pathogens such as S. pneumoniae , N. meningitidis , and Salmonella spp.; determine the feasibility

of routine isolate submission for validation of antimicrobial susceptibility

data submitted to NHSN ( ongoing ). f) Implement (2011) and analyze ( ongoing ) a periodic national prevalence s urvey for healthcare
- associated infections, including those caused by antimicrobial
- resistant pathogens
. g) NEW: The U
. S
. Army's Multidrug
- resistant organism Repository and Surveillance Network (MRSN) at the Walter Reed Arm y Institute of Research in Silver Spring, MD will assess existing and new PCR and other technologies to more accuratel y monitor the burden of antimicrobial resistance in the global Military Health Sy stem and support infection control programs (2012). h) NEW: De velop anal yt ic tools in NHSN for State D epartment of Health (and any group user) to evaluate summary resistance of reported HAIs b y group (i.e., state) allowing regional and state - level comparisons of HAI
- related summary data (2013); report on geographic v ariability

in resistance rates among HAI s in U.S. by 2013
. Coordinator: CDC; Collaborator: VA , DoD 1.3 Assess the presence of antimicrobial
- resistant microorganisms, such as MRSA, C. difficile , and vancomycin
- resistant enterococci (VRE), among food animals, retail meats, and household environment in the United States. Assessment should include comparison of isolates from humans , environment, retail meats, and food animals. a) Completed: See Appendix A. b) Completed: See Appendix A. c) Completed: See Appendix A. d) Co mpleted: See Appendix A.- 16
-

e) NEW: Asses s the prevalence of C. difficile in livestock on farms throughout the United States (2012). Coordinator: CDC; Collaborators: FDA, USDA 1.4 Id entify

patient populations colonized or infected with antimicrobial
- resistant pathogens which may

be important both for transmission of pathogens themselves and the transfer of resistance genes (e.g. vancom ycin
- resistant Staphylococcus aureus ). Use this information to develop prevention strategies. a) Id entify

populations at risk fo r C
. difficile and MRSA infections based on data from population
- based surveillance s ys tems (2013). b) Conduct (2012) and analyze (2013) studies of colonization with antimicrobial
- resistant S. pneumonia e to determine the effects of antimicrobial use and pneumococcal vaccination on colonization
. c) NEW: The U
. S
. Army's Multidrug
- resistant organism Repository and Surveillance Network (MRSN) at the Walter Reed Arm y Institute of Research in Silver Spring, MD will track the occurrence of multidrug resistant organism s in Military Health Sy stem (MHS) facilities and assess movement of these organisms in the MHS and interactions between these organisms (ongoing). d) NEW: The U
. S
. Army's Multidrug
- resistant organism Repository and Surveillance Network (MRSN) at the Walter Reed Arm y Institute of Research in Silver Spring, MD will conduct surveillance for and assess multidrug resistant organism in military working dogs (ongoing). Coordinator: CDC; Collaborator: NIH, VA , DoD 1.5 Strengthen and expand multi
- state, national , an d international surveillance sy stems for antimicrobial
- resistant microorganisms and ensure adequate sentinel surveillance for the emergence and spread of critical resistance phenoty pes (e.g., penicillin
- resistance in Group A Streptococcus , multidrug
- resist ant and extensively drug
- resistant tuberculosis [ XDR TB ] , oseltamivir
- resistant influenza viruses), and strive for more timely dissemination of surveillance data. a) Increas e the number and capacity of public health laboratories that routinely monitor for in fluenza antiviral resistance by d evelop ing new assay s for rapid testing for antiviral resistance (2011) and de velop ing web
- based reporting s ys tems (2012). b) In crease the capacity

of state public health laboratories to identify antimicrobial
- resistant organ isms among cases of culture
- negative clinical sy ndromes (e.g., meninigitis, empyema) using real
- time poly merase chain reaction (PCR) for species
- specific genes and markers of antimicrobial resistance (2013).- 17
-

c) Routinely

evaluate and monitor isolates captured through ABCs with unusual resistance profiles (e.g., penicillin
- resistant Group A or Group B Streptococcus , or vancomycin resistance among any of the Streptococcus pathogens) to identify resistance and characterize the molecular and genetic mechanisms ( ongoing). d) Completed: See Appendix A. e) Completed: See Appendix A. f) Completed: See Appendix A. g) NEW: Evaluate s tate - based laboratory surveillance and associated public health response for MDROs using established meaningful use criteria for electronic laboratory reporting (ELR) in states that have made CREs notifiable ; assess considerations for integration with NHSN (2015). Coordinator: CDC; Collaborators: DoD, FDA, USDA, VA 1.6 Work with public health associations, including Association of Public Health Laboratories (APHL) and Council of State and Territorial Epidemiologists (CSTE), to define minimal surveillance activities for AR for local, state, and regional health departments. Enhance the accurate detection and identification of AR b y cl inical and public he alth laboratories. a) Develop consensus definitions for outbreaks of antimicrobial
- resistant pathogens that are reportable to health departments to optimize the detection, investigation , and resolution of outbreaks (ongoing). b) Completed: See Appendix A. c) Implement standard protocols for antimicrobial susceptibility testing through CDC’s ELC Program (ongoing). d) Completed: See Appendix A. e) Establish a web
- based training program, updated annually , on laboratory detection of AR (pilot in 2013 and implement in 2 014). f) NEW: Inanticipation of the shift to culture
- independent testing, catalog and prioritize resis tance genes and other relevant genetic elements that can help predict clinical resistance in particular enteric pathogens and develop sentinel approaches f or monitoring this resistance in the population (2014). Coordinator: CDC- 18
-

1.7 Promote participation of microbiologists and local, state, and national public health workers in the design of sy stems to collect and disseminate AR data to appropriate end
users. Identify

methods to assist laboratories in summarizing and disseminating AR data to appropriate end
- users and provide methods for individual laboratories to compare their data with data in surrounding regions. a) Establish state
- based surveillance networks utilizing NHSN to aggregate local
- level data on healthcare
- associated infections, multidrug
- resistant organisms, and/or C. difficile infections for targeted prevention interventions (ongoing)
. b) Coordinate the collection of AR data for select veterinary bac terial pathogens by partnering with s tate veterinary diagnostic laboratories (2011). c) NEW: Assess the feasibility of coll ec ting data on selected animal pathogens through state veterinary

diagnostic laborato ries and other private entities (2012)
. Coordinator: CDC; Collaborators: FDA, USDA, VA 1.8 Collaborate with surveillance s ys tems in other parts of the world to build global surveillance of AR microorganisms. a) Establish liaisons with reference laboratories in countries without well
- developed surveillance s y stems, both to improve the accuracy of global surveillance for resistance and to improve local use of the data (ongoing). b) S upport and assist WHO on matters related to integrated surveillance of AR and containment of food
- related AR through participation i n the newly establish WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (WHO
AGI SAR) ( ongoing ).
 NARMS scientists from FDA, CDC , and USDA will provide expert advice to the WHO
- AGISAR steering committee through participation and info rmation sharing (2012)
.  Support laboratory

capacity building activities in WHO member countries for AR monitoring by

developing AR modules for Global Foodborne Infections Network training courses (2011
- 2012 )
. c) Develop collaborations with International Emer ging Infections Program (IEIP) sites to improve surveillance s ys tems for AR, facilitate prevention programs, and ensure appropriate responses to outbreaks of resistant organisms (ongoing). d) Collaborate with IEIP sites to expand surveillance sy stems (2011) to measure the burden of AR and the impact of infection control interventions in healthcare settings and conduct carriage studies (2014) in the community setting.- 19
-

Coordinator: CDC; Collaborators: DoD, FDA, USDA 1.9 Develop national and international surveil lance s ystems to monitor understudied areas, such as resistance in protozoan parasites (e.g. Plasmodium spp.) , helminthes or understudied sexually

transmitted diseases (e.g., T. pallidum, T. vaginalis , Herpes simplex), neglected tropical diseases, and resi stance to disinfectants, sanitizers, and insecticides. a) Id entify

resistance mechanisms in Trichomonas and use this information to develop laboratory

tests for detection of resistance ( 2012)
. b) Id entify

and characterize markers of artemisinin
- based combinati on therapies (ACT) resistance in malaria for the purpose of developing new laboratory tests for surveillance (2012)
. c) W ork with international partners to conduct in vivo / in vitro studies to monitor the efficacy of anti
- parasitic drugs (2013)
. d) Collect a repository

of specimens with characterized antimalarial drug sensitivity p atterns for the development of laboratory test development and quality control (2012)
. Laboratory

tests will be used to expand surveillance. e) Work with international partners to improve laboratory capacity in endemic countries for the detection and surveillance of malaria drug
- resistant parasites (2012)
. f) E valuate current strategies for deploying insecticides for public health that reduce or minimize resistance , and , as necessary , develop new strategies (2012). g) NEW: Conduct studies to assess the efficacy of transmission blocking interventions to reduce spread of resistant P. falciparum strains (2012
- 2014). h) NEW: Work with host national s to identify as ymptomatic carriers of drug re sistant P. falciparum via active case detection (ongoing). Coordinator: CDC; Collaborator: DoD 1.10 Assess the risk of AR emergence and spread in food borne pathogens due to environmental contamination by antimicrobial drug residues and pesticides in collaboration with the existing Pharmaceuticals in the Environment Subcommittee of the Office of Science and Technology Policy
. Coordinator: FDA; Collaborator: EP A Goal 2: Better define, characterize, and measure the impact of antimicrobial use in humans and anim als in the United States.- 20
-

2.1 Id entify

sources of antimicrobial use information in the United States for humans, animals, agriculture, aquaculture, and other sectors to establish baseline data on antimicrobial use. Develop a standard for collecting and repo rting sche mes for antimicrobial use data that allow aggregation, reporting, and comparisons of trends across sectors. a) Gain access to and summarize de
- identified data on antimicrobial use from market research companies, health maintenance organizations, f ederal healthcare systems, and other medical care s ys tems in the United States to aid in quantifying antimicrobial use in humans and understanding geographical heterogeneity in antimicrobial use (ongoing)
. b) Perform a national antibiotic use point
- prevalenc e survey . P ilot survey to be completed by 2010 and full survey

by 2012. c) Revise the Antibiotic Use and Resistance module of NHSN to accept electronic data on antibiotic use from healthcare facilities by 2011 and begin receiving data by 2012. d) Completed: S ee Appendix A. e) Completed: See Appendix A. f) NEW: Pilot (2012) and implement (2013
- 2014) national prevalence survey of appropriate antimicrobial use utilizing tools developed in 4.1a, and utilize infrastructure in 2.1b. g) NEW: Conduct national studies to det ermine antimicrobial use practices in livestock and poultry populations throughout the United States through the USDA:APHIS National Animal Health Monitoring S ys tem (ongoing)
. Coordinator: FDA, CDC; Collaborators: USDA , VA 2.2 Develop mathematical models to guide studies of use and resistance in both humans and animals by

collating existing data on correlations between antimicrobial use and antimicrobial resistance from studies in veterinary and human healthcare settings (e.g., cephalosporin use and prevalen ce of vancom ycin
- resistant enterococci in intensive care units) and community

settings (e.g., fluoroquinolone use for respiratory tract infections and macrolide resistance in pneumococci). a) Completed: See Appendix A. b) NEW: Explore metagenomic approaches t o understand ecology of resistance determinants in enteric organisms (2015). c) NEW: Compare the relationship between antibiotic prescribing and C. difficile disease rates (2013).- 21
-

d) NEW: Compare the relationship between antibiotic use and invasive S
. pneumo nia in the era of expanded
- valent pneumococcal conjugate vaccines (2013)
. Coordinator: CDC

; Collaborators: USDA , VA 2.3 Implement s ys tems to detect the development and spread of resistance in microorganisms during implementation of new programs that significa ntly impact antimicrobial drug use (e .g., pay- for
- performance mandates on antibiotic timing for community
- acquired pneumonia , gu idelines for intrapartum prophylaxis to prevent neonatal group B streptococcocal disease, mass population
- based treatment campai gns for trachoma or helminthic infections, or large studies of treating partners or contacts). a) Monitor the use of intrapartum antimicrobial prophylaxis for the prevention of neonatal group B streptococcal infections and the potential impact of prophylaxi s on resistant cases of neonatal sepsis (2013). Coordinator: CDC- 22
- 

### Focus Area II: Prevention and Control **Overarching goals** Federal agencies are strong advocates of prevention and control measures that will both decrease the development of new resistant microorganisms and stop the transmission of existing resistant microorganisms in healthcare institutions, communities, and agriculture. Goal 3
. Develop, implement, and evaluate strategies to prevent the emergence, transmission, and persistence of drug
- re sistant microorganisms. 3.1 Implement and evaluate the impact of community
- based interventions, such as vaccination campaigns and the promotion of appropriate antibiotic use to reduce the spread of AR microorganisms, rates of disease, and antimicrobial use, and to improve patient outcomes. a) Estimate the effectiveness of pneumococcal and influenza vaccines on drug
- resistant infections caused b y those pathogens (2013 ). b) Completed: See Appendix A. c) NEW: E valuate the impact of electronic clinical decision suppo rt on prescribing practices in ambulatory

care settings (2014). d) NEW: Provide support to state health departments to implement appropriate antibiotic use campaigns and interventions and evaluate their impact ( ongoing ). e) NEW: Coordinate the annual health ob servance Get Smart About Antibiotics Week in collaboration with state and local health departments, international health agencies, professional organizations , and private corporations to increase awareness about antibiotic resistance and improve antibiotic use (ongoing). Coordinator: CDC

; Collaborators, DoD, VA 3.2 Promote use of appropriate interventions, including checklists, to reduce the risk of infection associated with catheters and other devices and procedures in healthcare settings. a) Facilitate mul ticenter prevention collaborative focused on device and procedure
- related infections in at least 20 states by 2012. b) Completed: See Appendix A. c) Completed: See Appendix A.- 23
-

d) Completed: See Appendix A. e) Completed: See Appendix A. Coordinator: CDC

; Collabora tors: AHRQ, VA 3.3 Id entify

and promote successful AR prevention and control programs in healthcare settings that utilize existing recommendations for preventing transmission of AR organisms. a) Establish state
- based MDRO and C. difficile prevention collaborativ e in at least 10 states by 2011 and evaluate impact by 2013. b) Completed: See Appendix A. c) Completed: See Appendix A. d) Completed: See Appendix A. Coordinator: CDC

; Collaborators: AHRQ, VA, CMS 3.4 Evaluate the effectiveness of infection
- control practices, products, and devices in healthcare facilities, including long
- term healthcare and outpatient settings. a) Completed: See Appendix A. b) Initiate studies (2011), collect and process samples (2012), and anal yz e data (2013) to establish standardized methods and ba seline levels of contamination of healthcare environmental surfaces. These standardized methods and baselines will be used by industry and other partners to evaluate the dy namics of contamination and in demonstrating the ability of cleaning and disinfectio n methods to reduce transmission of AR pathogens. c) Evaluate the impact of state
- based CDC
- funded HAI prevention collaborative s by 2013. d) Quantify

the national impact of HAI prevention efforts by publishing annual national summary statistics (standardized i nfection ratio) of HAI data reported to CDC’s NHSN (ongoing). Coordinator: CDC

; Collaborators: AHRQ, DoD, VA 3.5 Id entify

factors that reduce transmission of drug
- resistant pathogens, including infection control, in veterinary , agriculture and aquaculture settings (ongoing). a) Id entify

critical control points on
- farm for dairy production that will decrease antimicrobial resistant s almonella e (2011). Evaluate interventions in dairy production that will de crease antimicrobial resistant s almonella e (2012).- 24
-

b) Make available grant funds of up to $4 million through USDA’s National Integrated Food Safety Initiative to support sy stematic studies that identify intervention strategies for effective mitigation of AR throughout the food chain. These 4
- year grants began in 20 10 and will be completed no later than 2015. c) Completed: See Appendix A. d) NEW: A sy stems approach will be employed to understand and characterize the host
pathogen interactions that are manipulated in food animals using novel therapeutic approaches with B T peptides (immunomodulators) and CpG oligonucleotides without engendering antimicro bial resistance ( 2013
- 2015)
. e) NEW: ARS researchers at College Station, TX, showed that day
- old birds of an immunologically

efficient genetic line of chickens were much more resistant to colonization by Salmonella enteritidis than were birds of a less immunologically efficient line. These researchers demonstrated that certain enzy mes in the birds (protein kinases) and the relevant signaling pathway s did in fact contribute to the pathogen resistance patterns exhibited in the different bird lines. The work is important because it has identified key

regulatory

points that can be targeted in genetic selection for pathogen
resistant and possibly

even pathogen
- immune commercial po ultry (2015). f) NEW: ARS researchers in Ames, IA, have identifi ed a gene (poxA) in Salmonella t yphimurium that, when mutated, dramaticall y reduces the ability of the bacterium to survive numerous stress conditions as well as antibiotic and chemical exposure s. Furthermore, the gene mutation decre ased the ability of S
. t yphimurium to colonize the pig. As this genetic s ys tem is c ritical for the ability of the s almonella e to cause disease and resist antibiotics, it offers a novel target mechanism for interventio n development against s almonella e (possible vaccine) (2013). g) NEW: Conduct workshop to solicit input from stakeholders on insights into the issues and information gaps that exist in the areas of antimicrobial use and resistance monitoring, practices to sup port judicious antimicrobial use, alternatives to antibiotics, and the discovery

of new antimicrobials (2012). Coordinators: FDA, USDA 3.6 Promote research and development of processing technologies to minimize microbial contamination of food. a) Develop alter

natives to current antimicrobial treatments and sanitizers for processing poultry carcasses (e.g. natural Generall y Recognized as Safe [GRAS] products) (2011). Evaluate alternative sanitizers for poultry processing and their reduction of food pathogens (20 12).- 25
-

b) Develop alternatives to current processing treatments for the reduction of E
. coli in beef (2011). Evaluate effectiveness of processing treatments (2012). c) Id entify

processing interventions to decrease antimicrobial
- resistant microorganisms in eggs (2011). Evaluate alternative interventions in egg processing for reduction of antimicrobial
- resistant microorganism (2012). Coordinator: USDA 3.7 Expand public health education campaigns targeting food producers, food handlers, and the general public about foo d safety practices that reduce microbial contamination of food. a) Completed: See Appendix A. b) Completed: See Appendix A. c) Completed: See Appendix A. d) NEW: L aunched the Food Safety Families Campaign (developed by USDA, FDA, CDC, and the Ad Council) in Engli sh and Spanish, to target parents and caregivers of young children (2011). The launch news release reached over 26 million people while broadcast co verage reached 13 million. In FY 2012, a Thanksgiving media tour with the Under Secretary for Food Safety

ge nerated more than 190 TV and radio segments nationwide, reaching 20.3 million people. Continue to expand campaign outreach (2012). e) NEW: Develop three consumer applications for smartphones to reach consumers with the latest, most up
- to - date food safety inf ormation (2012). f) NEW: Through the internet and other mechanisms, educate food producers, food handlers, and the general public about the major sources and ecology of resistant and susceptible bacterial enteric infections in humans (2014). g) NEW: Educate co nsumers about food safety through the USDA Food Safety Discovery Zone, launched in 2010, which travels throughout the United States visiting community events (ongoing). h) NEW: Conduct food safety education events in Washington D.C. for National Nutrition Mo nth (ongoing). Coordinator: USDA , FDA, CDC 3.8 Promote infection control education at all stages of training and practice for healthcare workers in human and veterinary medicine. a) Completed: See Appendix A. b) Completed: See Appendix A.- 26
-

Coordinator: CDC; Co llaborator: USDA , VA 3.9 Develop interagency programs in collaboration with regulators, payers, professional societies and other stakeholders to promote effective hand hygi ene strategies in communities and healthcare settings and to foster the use of biomedical devices and behaviors that prevent the transmission of infectious organisms in community settings. a) Completed: See Appendix A. b) Completed: See Appendix A. Coordinator: CDC

; Collaborator: AHRQ, VA Goal 4 : Develop, implement, and evaluate strategies to improve appropriate antimicrobial use. 4.1 Id entify

factors and strategies that promote appropriate antimicrobial use (i.e., best practices) or discourage inappropriate use in all types of healthcare settings, including inpatient and outpatient facilities, clinics and offices. Facilitate the implementation of these strategies. a) Develop algorithms and reporting tools to facilitate local monitoring of antimicrobial use (pilot 2011 and implement 2012) an d resistance rates (pilot 2011)
. b) Completed: See Appendix A. c) Completed: See Appendix A. d) Completed: See Appendix A. e) Examine the impact of improved antimicrobial use on adverse events associated with antimicrobials, especiall y C. difficile infections by 2011. Two manuscripts will be developed in 2012. f) Evaluate the benefits and potential unintended consequences of clinical guidelines and policies that bear on antimicrobial use and affect patient care, reimbursement, and other areas of medical practice (e.g., increased use of antimicrobial agents in emerg ency rooms for unconfirmed community
- acquired pneumo nia) (2014 ). g) NEW: Explore feasibility of correlating outpatient antimicrobial use with incidence of community
- based C. difficile infection to inform efforts at reducing infection through community
- based stewardship (2013). h) NEW: Examine knowledge, attitudes and behaviors of healthcare providers regarding antibiotic choice (2013).- 27
-

Coordinator: CDC

; Collaborators: AHRQ, FDA, VA 4.2 Promote, implement, and evaluate guidelines for appropriate antimicrobial use in agricultural and veterinary settings. Specifically , a) Seek appropriate expert input to update specific aspects of guidance 152 (particularl y the antimicrobial drug ranking in Appendix A of guidance) and publish revised draft guidance for public comment (2011
- 2012 ). b) Completed: See Appendix A. c) Completed: See Appendix A. d) Survey

orchards periodically

for emerging resistance among agricultural bacterial plant pathogens (e.g., Erwinia amylovera , Pseudomonas syringae , and Xanthomonas campestris ) to tetracycline, streptomycin, gentamicin, or other antimicrobial agents that may be used, such as kasugam ycin. Monitoring is conducted to compl y with pesticide use authorization. e) NEW: Develop or update educational materials on the judicious use of antimicrobial ag ents in food animals and make those materials available to veterinarians, veterinary students, and food animal producers (2014). f) NEW: Implement and maintain an education module on judicious antimicrobial use for veterinarians through the USDA: APHI S Natio nal Veterinary Accreditation Program ( ongoing ). Coordinators: FDA; Collaborators: CDC, USDA , EPA 4.3 Promote the development of improved field
- based methods to measure the quality of antimalarial drugs , given that poor quality drugs contribute to antimicrob ial drug resistance
. Coordinator: CDC 4.4 Develop, implement, and evaluate treatment algorithms for management of common clinical sy

ndromes frequently

treated with antibiotics (e.g., ventilator
- associated and community
- acquired pneumonia, acute bronchitis and sinusitis, and asy mptomatic bacteriuria and sexually

transmitted diseases )
. a) Update the Principles of Judicious Use of Antimicrobial Agents for Pediatric Upper Respiratory Infections and develop and disseminate academic detaining sheet with diagnosi s and treatment algorithms (2013 ).- 28
-

b) Update the Guidelines for Appropriate Antibiotic Use for Treatment of Acute Respiratory Tract Infections in Adults and develop and disseminate academic detailing sheet with diagnosis and treatment algorithms (2014). Coordinator: CDC

; Collaborator: NIH, VA- 29
- 

### Focus Area III: Research **Overarching goals** Encourage, conduct , and support basic and translational research to enhance our understanding of factors leading to the development of AR microorganisms, their transmis sion in various settings, and optimal modes of prevention, diagnosis , and therap y. Goal 5: Facilitate basic research on AR. 5.1 Conduct and support genetic, biochemical , and structural s tudies of AR factors to enabl e the identification of novel drug , diagnos tic , and vaccine targets. Coordinator: NIH 5.2 Investigate naturally occurring mechanisms of resistance, gene transfer, and host
pathogen interactions. Coordinators: CDC, NIH; Collaborators: FDA, USDA 5.3 Investigate the role of biofilms in the development o f resistant microorganisms and transfer of resistance genes among diverse genera of microorganisms. Coordinators: CDC

, NIH; Collaborator

s : FDA, USDA 5.4 Develop and make available genomics, metagenomic, bioinformatics, proteomics, structural biology , molecul ar imaging, and other emerging research technologies. Ensure that genomic, proteomic, and other related data sets are made publicl y available rapidl y through searchable public online databases and provide data analy sis tools to assist researchers in using these resources. Coordinator: NIH

; Collaborators: CDC, DoD, FDA, USDA 5.5 Bring new researchers into the field by utilizing appropriate strategies such as training and research opportunities. Coordinators: CDC, NIH ; Collaborator: FDA Goal 6 : Facilitate the translation of basic research findings into practical applications for the prevention, diagnosis and treatment of resistant infections. 6.1 Facilitate preclinical studies, including toxicology , pharmacokinetics, pharmacodyn amics, and in vitro and in vivo act ivity of antimicrobial agents to inform the treatment of resistant pathogens. Coordinator: NIH

; Collaborators: CDC, FDA- 30
-

6.2 Encourage, support , and conduct basic and clinical research on the development and use of vaccines and novel or alternative approaches f or prevention and treatment of infections in human and veterinary

medicine. Coordinators: NIH, USDA; Collaborators: CDC, DoD, FDA 6.3 Encourage, support , and cond uct research on the development of novel diagnostic technologies to rapidl y distinguish among pathogens and their resistant subty pes at the point of care. Coordinator: NIH 6.4 Support development of novel broad spectrum antimicro bials with dual indications for communi ty

and hospital acquired infections and biodefense threat agents. Coordinator: AS

PR/BARDA; Collaborator: NIH , CDC Goal 7: Facilitate clinical research to improve the treatment and prevention of AR infections. 7.1 Conduct and support c linical research to evaluate the safety and efficacy of novel drugs and vaccines for pathogens where resi stance threatens effective treatment. Coordinator: NIH 7.2 Design and implement studies focused on optimizing the dose and duration of antibacterial agents prescribed for treatment of community
- acquired pneumonia, urinary tract infections, skin and soft
- tis sue infections, and other infectious illnesses. Coordinator: NIH Goal 8: Conduct and support epidemiological studies to identify key drivers of the emergence and spread of AR in various populations. 8.1 Investigate the interplay among AR, colonization, and disease in acute, long
- term care, and outpatient facilities. Coordinator: CDC

; Collaborator: NIH, VA 8.2 Support research on how prevalence data on antimicrobial resistance can be used to help guide treatment choices. For example, define geographic heterogene ity of resistance rates and determine impact of treatment decisions. a) Define appropriate methods for collection and distribution of information on prevalence of resistance to community phy sicians and veterinarians. b) NEW: Develop capacity in developing co untries to conduct genomic and bioinformatics
based molecular epidemiological studies to inform public health drug resistance containment and elimination efforts (ongoing)
.- 31
-

Coordinator: CDC

; Collaborators: FDA, USDA, VA 8.3 Evaluate the utility of monitoring s entinel human populations (e.g., farm, abattoir, fruit and vegetable, and food processing plant workers) and persons in the general community for infection or colonization with resistant enteric bacteria to identify reservoirs of resistant organisms. a) Inve stigate risk factors for AR development in Salmonella and Campylobacter in food animals (2014). Coordinator: CDC

; Collaborator: FDA, USDA 8.4 Develop options to capture and record AR research for all federal agencies. Coordinators: CDC

, NIH ; Collaborators: A HRQ, EPA, FDA , USDA- 32
- 

### Focus Area IV: Product Development **Overarching goals** Encourage the development of new antimicrobial products to improve our capacity to diagnose, prevent and treat infections, including infections caused b y resistant microorganisms. Goal 9: Provide information on the status of antibacterial drug product development and clarify recommended clinical trial designs for antibacterial products. 9.1 Examine trends over time for new drug applications for sy stemic antibacterial drugs. a) Perfo rm pilot phase of study to evaluate trends over time for new drug applications for sy stemic antibacterial drugs; complete assessment of trends over time for new drug applications for s ys temic antibacterial drugs (2011) and publish findings (2012). Coordin ator: FDA 9.2 Publish guidance documents for the following conditions describing recommended approaches on clinical trial designs for evaluating antibacterial drugs. a) Publish guidance on recommended approaches to clinical trial designs for evaluating antibacterial drugs for acute bacterial ski n and skin structure infections (2012). b) Publish guidance on recommended approaches to clinical trial designs for evaluating antibacterial drugs for h ospital
- acquired and ventilator
- associated bacterial pneumonia (2012 ). c) Publish updated guidance on recommended approaches to clinical trial designs for evaluating antibacterial drugs for community
- acquired bacterial pneumonia. Publ ish updated draft guidance (2011 ) and final guidance (2012)
. Coordinator: FDA 9.3 Pub lish guidance documents for the following typ es of devices to provide recommendations regarding product development. a) Publish final guidance document on premarket notification [510(k)] submissions for medical devices that include antimicrobial agents (2012 ). b) Publish draft guidance for establishing performance for in vitro diagnostics assay s for MRSA and VRE (2011). Publish final guidance (2012)
. c) Publish draft guidance document for establishing performance for in vitro diagnostic assay s for C. difficile
. P ublish final guidance (2011)
. Coordinator: FDA 9.4 Provide regulatory advice on recommended regulatory pathway s for evaluating products that target unmet medical or veterinary needs including approaches to evaluating non
traditional products, e.g., cy tokine, probiotics, and antimicrobial peptides (ongoing).- 33
-

Coordinator: FDA; Collaborator: USDA 9.5 Evaluate use of the Orphan Drug Act, or similar incentives, to encourage development and marketing of new antimicrobial agents for human medicine. a) Comp leted: See Appendix A. Coordinator: FDA 9.6 Sponsor a study

to evaluate incentives to promote the development of antibacterial drugs for human use and rapid diagnostic tests (including antimicrobial susceptibility tests), including the impact of such strategies upon appropriate use of such products. Prepare a report for publication describing the study results (2012). Coordinator: HHS/ASPE Goal 10: Consider opportunities for international harmonization and means to update susceptibility

testing inform ation for human and animal use. 10.1 Pursue interagency collaborations to discuss international harmonization of standards and regulatory

requirements for antimicrobial products (e.g., International Conference on Harmonization, International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medical Products) (ongoing). Coordinator: FDA 10.2 Collaborate with relevant international organizations and use international expert consultations (e.g., the WHO, the World Organization on Animal Health, CLSI standards Institute, the European Committee on Antimicrobial Susceptibility Testing) to enhance product development (ongoing). Coordinator: FDA 10.3 Develop a strategy for periodic updating of susceptibility testing inform ation for antimicrobial agents approved for use in humans and animals in the United States (ongoing). a) Participate in multi
- laboratory method trial studies t o develop standardized in vitro antimicrobial susceptibility testing methods for veterinary pathog ens where such tests are lacking (2011)
. Coordinators: CDC, FDA ; Collaborator: USDA Goal 11: Encourage development of rapid diagnostic tests and vaccines. 11.1 Encourage development, testing, and evaluation of new rapid diagnostic methods for human and veterinary

use to help guide antimicrobial therapy . Specifically, promote the development of tests for infections cause b y fastidious (e.g. TB ) or difficult to culture organisms (e.g. Treponema pallidum , the agent of sy philis) and rapid point
- of
- care- 34
-

diagnostics to identify

patients with viral respiratory infections who do not need antimicrobial agents. a) Encourage improved diagnostic tests for resistant TB b y conducting a FDA/CDC/NIH co - sponsored meeting to identify gaps in TB diagnostics and to explore mo dels and strategies that may

expedite the development of new diagnostics (2010). Work to develop, evaluate, and implement molecular tests for the detection of MDR
- TB directly from pulmonary

specimens (2012). b) Encourage development of rapid point
- of
- care t ests to confirm diagnoses of possible bacterial respiratory

infections including otitis media, sinusitis, and pneumonia and to identify pathogens associated with these infections (ongoing). c) Completed: See Appendix A. Coordinators: CDC, FDA ; Collaborators : NIH, USDA , VA 11.2 Encourage development, testing, and evaluation of new vaccines for human pathogens for which AR poses a significant problem for treatment or public health. a) Working with stakeholders, examine strategies to maximize the quality and the quantity of candidate vaccines for prevention of antimicrobial
- resistant infections of public health significance (ongoing). b) Conduct research to facilitate development of vaccines for resistant pathogens such as Staphylococcus aureus, Mycobacterium tu berculosis, C. difficile, enteric pathogens , and Neisseria gonorrhoeae (ongoing). c) Conduct research to facilitate development of vaccines for viral respiratory infections that may contribute to increased antibiotic use due to subsequent or co
- bacterial in fections or inappropriate antibiotic use (ongoing). Coordinator: FDA ; Collaborators: CDC, NIH, VA 11.3 Completed: See Appendix A.- 35
- 

### Acronyms and Abbreviations AHRQ Agency for Healthcare Research and Quality APHL Association of Public Heal th L aboratories AR Antimicrobial re s istance ASH Office of the Assistant Secretary for Health (HHS) ASPE Office of the Assistant Secretary for Planning and Evaluation ASPR Office of the Assistant Secretary for Preparedness and Response (HHS) BARDA Biomedical Advanced Research Development Authority CDC Centers for Disease Control and Prevention CL SI Clinical and Laboratory Standards Institute CMS Centers for Medicare and Medicaid Services CSTE Council of State and Territorial Epidemiologi sts DoD Department of Defense EPA Environmental Protection Agency FDA Food and Drug Administration HAI Healthcare
- associated infection HAP Hospital
- acquired pneumonia HHS Department of Health and Human Services HRSA Health Resources and Serv ices Administration IPEC Inpatient Evaluation Center MDRO Multidrug
- resistant organism MRSA Methicillin
- resistant Staphylococcus aureus NHSN National Healthcare Safety Network NIH National Institutes of Health USDA United States Department of Agriculture VA Department of Veterans Affairs VAP Ventilator
- associated pneumonia VHA Veterans Health Administration XDR TB Extensively drug
- resistant tuberculosis- 36
-



### Appendix A: Retired Projects and Implementation Steps This Appendix lis ts all projects and implementation steps that the Task Force retired from the 2012 Action Plan. **Project Number**  **and Letter Project Description**  **Reason for Retirement**  1.1a Implement a multi
- site community
- onset pneumonia etiology

study among persons admitted with pneumonia and evaluate the specific role of antibacterial and antiviral resistance in determining outcomes associated with pneumonia (2011). Completed See 2011 Annual Progress Report 1.3a Design and implement a 1 year prevalence study of MRSA, VRE, and C. difficile from retail meat (2011). Completed See 2011 Annual Progress Report 1.3b Evaluate the quant ity of C. difficile recovered from retai l meats in FoodNet sites. Completed See 2011 Annual Progress Report 1.3c Evaluate the quant ity of C. dif ficile recovered from retai l meats in FoodNet sites. Completed See 2009

– 2010 Annual Progress Report 1.3d Conduct a pilot study to evaluate C. difficile environmental contamination in households of infected and non
- infected patients. Completed See 2011 Annual Progress Report 1.5d Assess the impact of including data on susceptibility to multiple fluoroquinolones and injectable agents (aminogl ycosides and capreomycin) to the national TB reporting s ys tem for enhanced detection of XDR TB. Completed See 2009

– 2010 Annual Progress Report 1.5e Complete a pilot exercise to expand routine nationwide

surveillance for MDR TB to include additional drugs and determine whether this additional surveillance provides useful information that warrants broader implementati on. Completed See 2009

– 2010 Annual Progress Report 1.5f Organize, plan and conduct a NARMS public scientific

meeting to highlight results and related AR research and solicit input from stakeholders and international partners on future enhancements and i mprovements . Completed See 2011 Annual Progress Report 1.6b Disseminate expert recommendations for effective state
- based

surveillance for multidrug
- resistant organisms related to healthcare
- associated infections. Completed See 2011 Annual Progress Report 1.6d Develop and implement an antimicrobial susceptibility testing training program for public health laboratories (2012). Completed See 2009

– 2010 Annual Progress Report- 37
-

2.1d Collect and publish annual reports on animal antimicrobial

drug distribution data through implementation of Section 105 of the Animal Drug User Fee Amendments of 2008 (2010 and ongoing). Completed See 2011 Annual Progress Report 2.1e Collect data through the National Animal Health Monitoring

Sy stem to produce 3 reports on antimicrobial use practices on livestock and poultry

operations in the United States. These reports (shown below) will be produced b y July 2011:

 Food Safety Pathogens Is olated from U.S. Dairy Operations, 1996
- 2007

 Antimicrobial Use and Resistance on Beef Cow
- calf Operations in the U.S. 2007
- 08

 Antimicrobial Use and Resistance Across Livestock and Poultry

Operations
- A compilation of data from the National Animal Health Monitoring Sy stem studies Completed See 2011 Annual Progress Report

2.2a Compare retail pharmac y sales of outpatient oral

antimicrobials to geographic differences in bacterial resistance (2011). Completed See 2011 Annual Progress Report 3.1b Evaluate factors that influence the prescribing practices of

primary care ph ys icians, including academic det ailing and benchmark anal ys is (2011). Completed See 2011 Annual Progress Report 3.2b Design and implement systems to measure healthcare

processes that are linked to outcome data in order to measure the adherence of healthcare personnel to prevention measures. Completed See 2011 Annual Progress Report 3.2c Correlation between adherence to best catheter insertion

practices and CLABSI rates (2011). Completed See 2011 Annual Progress Report 3.2d Revise and publish HI CPAC guidance for prevention of

catheter
- a ssociated bloodstream infections. Completed See 2011 Annual Progress Report 3.2e Revise and publish HI CPAC guidance for prevention of

surgical site infections (2011). Completed See 2011 Annual Progress Report 3.3b Evaluate impact of the CMS
- Quality Impro vement Organization MRSA prevention initiative by 2012. Completed

See 2011 Annual Progress Report 3.3c Evaluate impact of the Department of Veterans Affairs

National MRSA prevention initiative (2012). Explore the expansion of prevention initiatives to in clude other MDRO including C. difficile and multidrug
- resistant gram
- negative pathogens
. Completed See 2011 Annual Progress Report 3.3d Facilitate initiation of at least one regional, multi
- center

prevention collaborative in which acute and long
- term care Completed See 2011 Annual- 38
- facilities address prevention of multi
- drug resistant infections in a coordinated manner (2011). Progress Report 3.4a Expand CDC’s Prevention Epicenter Program to include

academic centers, integrated health sy stems, and healthcare departments to support early translation of technical advances and epidemiologic knowledge into evidence
- based recommendations (2011). Completed See 2011 Annual Progress Report 3.5c Id entify

factors important for assuring that antimicrobial drugs are u sed judiciously in veterinary , agriculture and aquaculture environments. Completed See 2011 Annual Progress Report 3.7a Co
- host the 2010 Food Safety Education Conference: USDA

and NSF International will co
- host a 3
- day conference sponsored b y HHS, FDA, CD C, and WHO. The conference is designed for attendees to share the most current research, learn best practices, and explore cutting
- edge strategies for reducing foodborne illness
. Completed See 2009

– 2010 Annual Progress Report 3.7b Launch new USDA Food S afety Mobile Program in spring 2010 as part of the Food Safety and Inspection Service’s ongoing consumer education campaign to reach consumers where they

live. The USDA Food Safety Mobile will travel throughout the United States visiting local community ev ents to educate consumers about food safety. The revamped program will offer consumers in
- depth, interactive, hands
- on Completed demonstrations on the science of food safety based on the four Be Food Safe Campaign messages: Clean, Separate, Cook and Chill. The Mobile’s interactive learning stations are designed to improve consumer’s food safety awareness, knowledge, and behavior
. Completed See 2011 Annual Progress Report

3.7c Host USDA Nutrition Month to inclu de Food Safety Day on March 10, 2010 to increas e consumer awareness about food safety . Completed See 2011 Annual Progress Report 3.8a Complete basic infection control curriculum for posting on

the CDC website by

2011. Completed See 2009

– 2010 Annual Progress Report 3.8b Develop a plan for infection control education of veterinary

medicine workers b y 2011. Completed See 2009

– 2010 Annual Progress Report 3.9a Develop a plan to collaborate with WHO on their hand

hygiene promotion campaign. Completed See 2011 Annual Progress Report 3.9b In collaborati on with academic partners, complete research

studies that evaluate the impact of novel technologies for measuring hand h ygiene adherence in the healthcare setting (2011). Completed See 2011 Annual Progress Report- 39
-

4.1b Develop a “change package” for improv ing antimicrobial use

in in
- patient healthcare settings
. Completed See 2011 Annual Progress Report 4.1c Collaborate with a network of hospitals to identify patient
level indications for and factors associated with antibiotic use to help guide efforts on i mproving use b y 2011. Completed See 2011 Annual Progress Report 4.1d Examine knowledge, attitudes, and behaviors of healthcare

providers regarding adverse events and antimicrobial use
. Completed See 2011 Annual Progress Report 4.2 b Publish and seek publ ic comment on draft guidance outlining

FDA’s current thinking on the judicious use of medically important antimicrobial drugs in food
- producing animals. Completed See 2009

– 2010 Annual Progress Report 4.2c Publish a revised order to prohibit certain extralabel uses of

cephalosporin antimicrobial drugs in food producing animals due to AR concerns (2011). Completed See 2011 Annual Progress Report 9.5a Part 15 public hearing held April 28, 2008, on issues in AR

and the Orphan Drug Act. Completed See 2009

– 2010 Annual Progress Report 11.1c Encourage development of rapid point
- of
- care tests to confirm diagnoses of possible bacterial respiratory infections including otitis media, sinusitis, and pneumonia and rapid point
- of
- care tests to identify

pathogens ass ociated with these infections (ongoing). Completed See 2009
- 2010 Annual Progress Report 11.3 Support advanced development of vaccines for resistant

pathogens such as Staphylococcus aureus. Work was not initiated and determined to be beyond the current sc ope of work at BARDA