Public Health Action Plan to Combat Antimicrobial Resistance
This 2012 update of the 2011 revision of the A Public Health Action 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 antimicrobial resistance. The past decade has seen extraordinary change in the microbiology and epidemiology of antimicrobial-resistant microbes and subsequent changes in treatment and patient outcomes. The Task Force is taking further strides to ensure that the Action Plan remains current and relevant as the agencies continue to look towards the future by taking the following steps:
- Actions, the numbered items that follow each goal, will be reviewed biennially by the Task Force beginning in 2013. New actions 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 Task Force agencies to continue to collaborate most effectively in achieving Action Plan goals.
- Implementation steps or projects, the lettered items that follow action items, are being revised annually. In this first annual update, new 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 yearly progress report for the year 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 Antimicrobial 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 the 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.
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 antimicrobial a resistance (AR) in recognition of the increasing importance of AR as a public health threat. The Task Force is co-chaired by 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 Services 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 Assistant Secretary for Health (HHS/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 delivery 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 Plan 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 consultants with wide-ranging expertise in areas such as human and veterinary medicine, pharmaceutical and diagnostics manufacturing, animal husbandry, clinical microbiology, epidemiology, and infectious diseases and infection control, and state and local public health officials.This 2012 update reflects changes since the 2011 Action Plan. The Action Plan includes 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:
- Goal 1: Improve the detection, monitoring, and characterization of drug-resistant infections in humans and animals.
- 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.
- 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: Provide information on the status of antibacterial drug product development and clarify 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 tests 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.
Introduction and Overview
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 resistance genes from other organisms and thereby develop resistance to antimicrobial drugs. When an antimicrobial drug is used, the selective pressure exerted by 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 medical advances of the last seventy years.
Drug-resistant pathogens are a growing menace to all people, regardless of age, gender, or socioeconomic background. They endanger people in affluent, industrial societies like the United States, as well as in less-developed nations. Examples of clinically 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 infections (e.g., Escherichia coli), foodborne infections (e.g., Salmonella or E. coli acquired from 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 phenotypes have emerged elevates the public health significance of this issue. In addition, the declining number of new antimicrobial agents limits treatment options, particularly for patients with infections caused by 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 not susceptible to penicillin. In addition, resistance to several other antibacterial drugs is common; 1.5 percent of isolates were resistant to cefotaxime (a "third-generation" cephalosporin antibiotic), and resistance to the newer fluoroquinolone antimicrobials has already been reported.b Nearly all strains of Staphylococcus aureus in the United States are resistant to penicillin, and many are resistant to newer methicillin-related drugs. Vancomycin for many years has been the only uniformly 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 vancomycin. The public health burden of methicillin-resistant Staphylococcus aureus (MRSA) is staggering, with over 90,000 invasive MRSA infections per year estimated in the U.S. population.c
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 cause 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 make 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 personnel 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 increasingly limited and expensive, and, in some cases, nonexistent.
Since their discovery, antimicrobials 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 treatment 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 can be relatively high. The impact of increases in resistant bacteria in food animals on 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 phenotypes.
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 microbes are increasingly appearing in new settings. MRSA, which for 30 years was almost exclusively a problem in hospitals, is now occurring in the community among otherwise healthy persons. g
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 increases. Individuals infected with drug-resistant organisms are more likely to remain in the hospital for a longer time, and to have poorer prognoses.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 stays were extended between 6.4 to 12.7 days, 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 significant health and economic benefits are possible through efforts to reduce antimicrobial resistance and healthcare-associated infections.
AR will always be with us. The challenge before us is to transform this increasingly urgent threat into a manageable problem. In the past, the Institute of Medicine, the American Society for Microbiology, the World Health Organization (WHO), the Congressional Office of Technology Assessment, the Government 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 by AR. In addition, a 2009 U.S.-EU Summit Declaration included a statement to establish a transatlantic task force 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 Federal and state governments and a willingness to address complex and sometimes controversial scientific, medical, and economic issues.
The Action Plan includes action items organized into four focus areas: Surveillance, Prevention and Control, Research, and Product Development. Each focus area contains 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
Unless AR problems are detected as they emerge and actions are taken quickly to contain them, the world may soon be faced with previously treatable diseases that have again become untreatable, as in the pre-antibiotic era. Early detection of new and emerging resistance, ongoing monitoring of resistant infections, 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 surveillance systems for antimicrobial-resistant microorganisms. Additional action items in this area focus on addressing barriers to timely dissemination and updating of surveillance data and gathering information on antimicrobial use practices.
Over the next few years, CDC will address several action items in this focus area by continuing to expand and improve its surveillance systems that collect data on AR. For instance, the National Healthcare Safety Network (NHSN) is a surveillance system that provides healthcare facilities a way to track, analyze, and interpret data on healthcare-associated infections (HAIs), including those caused by antimicrobial-resistant pathogens. NHSN is expanding to improve its capacity for collection and analysis of data on multidrug-resistant organisms (MDROs) and antimicrobial drug use. In addition to monitoring resistance in healthcare settings, CDC is maintaining surveillance activities for pathogens affecting the general population through efforts such as the Emerging Infections Program (EIP), a population-based network of CDC and state health departments, National Antimicrobial Resistance Monitoring System (NARMS), the Gonococcal Isolate Surveillance Project, and the National Tuberculosis Surveillance System. Through the EIP program, CDC closely monitors invasive bacterial pathogens through Active Bacterial Core surveillance. In partnership, FDA, USDA, and CDC track resistance among enteric pathogens through NARMS. On-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 continues to monitor resistance among non-bacterial pathogens such as influenza, malaria, and HIV, both domestically and internationally.
II. Prevention and Control
The prevention and control of antimicrobial-resistant infections requires measures to prevent the transmission of resistant microorganisms 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 by preventing or eliminating all infections caused by that microorganism. For 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 young children in the United States as recently as 15 years ago, but following the introduction of Haemophilus infuenzae serotype b (HIB) vaccines this problem has nearly been eliminated.
Action items in this area address extending the useful life of antimicrobial drugs by encouraging appropriate use through educational efforts such as the Get Smart: Know When Antibiotics Work campaigns, preventing 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 System and CDC demonstrating a reduction of MRSA infections, that initiative was expanded into an additional 17 sites within the Veterans 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 across the healthcare system and to fund research, implementation, measurement, and evaluation practices that mitigate healthcare-related infections.
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 action items covered in this 2012 AR Action Plan.
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 these processes and outcomes. Basic 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 area include support of basic research to uncover new targets and new antimicrobials, investigations into the development of resistance and host-pathogen interactions, optimization of treatment for resistant pathogens, and translation 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 supports 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 provide 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 readily accessible to the broader scientific community through publicly 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 phenotypes in the pathogen and in the human host. The bioinformatics resource centers provide the scientific community free access to resources for the query, analysis, and display of such information through user-friendly interfaces.
NIH currently supports clinical trials aimed at identifying ways 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 pneumonia, otitis media, skin and soft tissue infection, and bacteremia, and employ strategies to reduce use, such as shorter courses of antimicrobial treatment; using antimicrobials only where indicated; different dosages/frequencies to achieve desirable in vivo efficacy; validation of the key components of multi-drug therapy; and optimal use of off-patent antimicrobials to prevent the emergence of resistance.
IV. Product Development
There is a critical need for new drugs, vaccines, and diagnostic tests to treat, prevent, and diagnose infections, including serious and life-threatening 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 by 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 published 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 (HABP) and ventilator-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 Physicians, the Society of Critical Care Medicine, and the American Thoracic Society regarding scientific issues in clinical trial design for HABP and VABP. This public workshop provided information about and gained perspective from health care providers, academics, and industry on various aspects of antimicrobial drug development for HABP and VABP, including diagnosis, treatment, trial endpoints, and statistical issues in analysis of results of trials in HABP and VABP.
In the next few years, FDA will engage in activities 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 to 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 addition, FDA also plans to publish guidance for establishing performance for in vitro diagnostics assays for MRSA and vancomycin-resistant enterococci (VRE). These guidances will describe recommended approaches for developing new antimicrobial products for specific uses.
The Biomedical Advanced Research Development Authority (BARDA), in the HHS Office of the Assistant Secretary for Preparedness and Responseo 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 currently supporting the development of an intravenous formulation of a next-generation aminoglycoside antibiotic for the treatment of plague and tularemia, as well as ventilator-associated pneumonia. In 2012, 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 as diseases caused by clinically prevalent infectious diseases, including those that are antimicrobial resistant.
The Focus Areas
Following each of the goals listed for each focus area are several action items that define topic 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 and are indicated as such. Project lists will be updated annually, and actions will be updated every two years.
Focus Area I: Surveillance
In order to develop and implement effective control strategies there must be 1) continuous or periodic monitoring of infections caused by AR microorganisms and 2) comprehensive knowledge of the use of antimicrobial agents across all sectors.
Focus Area II: Prevention and Control
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.
Focus Area III: Research
Encourage, conduct, and support basic and translational research to enhance our understanding of factors leading to the development of AR microorganisms, their transmission in various settings, and optimal modes of prevention, diagnosis, and therapy.
Focus Area IV: Product Development
Encourage the development of new antimicrobial products to improve our capacity to diagnose, prevent and treat infections, including infections caused by resistant microorganisms.
Acronyms and Abbreviations
AHRQ Agency for Healthcare Research and Quality APHL Association of Public Health Laboratories AR Antimicrobial resistance 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 CLSI Clinical and Laboratory Standards Institute CMS Centers for Medicare and Medicaid Services CSTE Council of State and Territorial Epidemiologists 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 Services 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
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 applies to agents intended for healthcare, veterinary, and agricultural applications.
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.
d Update to CDC’s Sexually Transmitted Diseases 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, Petruccelli 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.
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 infections 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.
j These highlighted activities are provided as illustrative examples and do not represent a comprehensive list.
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 practice, 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 Initiative to Prevent Methicillin-Resistant Staphylococcus aureus Infections.” New England Journal of Medicine 364(15): 1419-1430.
m The HHS Action Plan to Prevent Healthcare-Associated Infections is available on the HHS website at: http://www.hhs.gov/ophs/initiatives/hai/infection.html
n Examples of recent guidance documents: Antibacterial Drug Products: Use of Noninferiority Studies to Support Approval (draft, October 2007), Acute Bacterial 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 Pulmonary 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).
o See http://www.phe.gov/about/barda/Pages/default.aspx for more information on BARDA.
p Because of the rapidly evolving nature of AR, there will likely be new or emerging challenges in antimicrobial resistance subsequent to the publication of this Action Plan. The Task Force is committed to identifying and responding to these issues as they arise.