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Issues Related to Antimicrobial Resistance


Statement of

Jane E. Henney, M.D.
Commissioner
Food and Drug Administration
Department of Health and Human Services

before

the Subcommittee on Labor, Health, and Human Services, and Education
Senate Committee on Appropriation

September 20, 2000

INTRODUCTION

Mr. Chairman and members of the Committee, I am Dr. Jane E. Henney, Commissioner of Food and Drugs, Food and Drug Administration (FDA or Agency). I am pleased to be here this morning to talk about issues related to antimicrobial resistance and FDA's important role in addressing this growing public health problem. While I understand the focus of this hearing is human drugs, my testimony also will include issues related to animal drugs and animal health.

Antibiotic resistance is well recognized as a major threat to the health of U.S. citizens and people around the world. Although we have been using antibiotics for more than 50 years, the extent of resistance is much greater than ever before. Antimicrobial resistance is a natural biological phenomenon that is the result of the rapid replication and evolution of microbes. When a microbial population is exposed to an antibiotic, the more susceptible organisms will succumb, leaving behind only the resistant organisms. Through this selective process, resistant organisms become more predominant throughout the microbial population. Microbes also commonly acquire genes, including those encoding for resistance, by direct transfer from members of their own species or, sometimes, from unrelated microbes. However, the likelihood of microbes developing resistance becomes magnified by widespread and often inappropriate antimicrobial use.

In addressing the antimicrobial resistance problem, FDA's goal is to be sure that practitioners have a continuous supply of safe and effective antimicrobials available to protect the health of both humans and animals, as well as reliable laboratory test products to rapidly direct appropriate antibiotic use.

Antibiotics are different from most of the other drugs approved by FDA, because their effectiveness is so fragile. Another unique characteristic is that these drugs affect not only the patient who receives them but also their personal contacts, the environment and the health of the community. We need to protect the effectiveness of this special class of drug products by using them in a thoughtful way that is based on the best available science. If these drugs are overused, or misused, their effectiveness will not be there when patients need them. We already have some infectious diseases where there are either no or few satisfactory therapeutic options because of antibiotic resistance.

We should look at our array of antibiotics as a valuable resource that deserves careful protection. And, as with most issues that involve fragile resources, this one has global ramifications. With frequent and wide-ranging air travel and extensive immigration, we are able to pass our pathogens to one another with frightening speed. That means that in order for us to succeed in our effort to use antibiotics wisely, similar steps must be taken by nations around the world. In some countries, antibiotics are available without prescription and may be impure or subpotent, and many patients cannot afford adequate courses of treatment. Not surprisingly, rates of resistance, particularly to common community acquired and food borne pathogens, are often even higher than in the United States (U.S.). This causes suffering and further demands on already overstretched resources abroad and poses risks to the U.S. through transport of resistant pathogens to our citizens. An example of this type of trans-national threat has been the spread of multi-drug resistant tuberculosis.

FDA TASK FORCE ON ANTIMICROBIAL RESISTANCE

As you know, FDA has key roles in helping facilitate the development of drugs, vaccines, devices and diagnostics as well as ensuring their safe and effective use. In addition, FDA has an important role in informing the public and health professionals of antibiotic resistance and principals of appropriate use through educational outreach, by assuring useful and accurate product labeling, and appropriate marketing. Traditionally, FDA has been active in addressing the resistance problem. However, to further stimulate and coordinate FDA's actions to combat antimicrobial resistance, in late 1998, an internal "FDA Task Force on Antimicrobial Resistance" (Task Force) was established to develop a clear consensus regarding what, given limited resources, should be the key priorities of the Agency.

While FDA saw the need to better coordinate and focus antimicrobial resistance activities within the Agency, it also recognizes that managing antimicrobial resistance requires coordinated actions and partnerships with many other entities, both within and outside the Federal government. FDA is privileged to co-chair with the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH) an Interagency Task Force on Antimicrobial Resistance that was formed in 1999 to develop a Public Health Action Plan to Combat Antimicrobial Resistance. The Public Health Action Plan will be briefly discussed later in my testimony.

The internal FDA Task Force Report, completed in draft in October 1999, focuses on issues and areas where FDA should and is able to play an important role in achieving specific and practical outcomes. Recommendations are in four key areas:

  1. Promptly and effectively responding to current threats from drug resistance;
  2. Facilitating and encouraging development and appropriate use of products which help address the issue;
  3. Facilitating the safe and effective use and thus prolonging the life of products by helping improve the quantity and quality of information available to consumers and health professionals regarding antibiotics resistance and principles of appropriate usage; and,
  4. Maximizing and coordinating FDA's scientific research to address needs in antimicrobial resistance.

Let me discuss each of these four key areas for addressing the problem of antimicrobial resistance.

EFFECTIVELY RESPONDING TO CURRENT PUBLIC HEALTH THREATS

Therapeutic options for resistant infections have become increasingly limited and, therefore, important to protect and preserve for these critical uses. In particular, there are agents, including among them both those recently or previously approved and those as yet unlicensed, which are either the only or among the very few available treatments for life threatening resistant infections. This concept of critical "Category I Drugs" is also embodied in the proposed Center for Veterinary Medicine (CVM) Framework. The proposed Framework document, which I will discuss later, outlines the categorization of drugs by their importance to human medicine as well as a risk-based Framework for their use in food animals.

How antibiotics are used could, as it has in the past, be regarded as primarily an issue of "medical practice." However, it is widely acknowledged that the rapidity of development of resistance to an agent is increased with the magnitude of antibiotic use. Thus, use of these precious drugs of last resort for infections easily treated by other medicines is highly likely to ultimately compromise their efficacy, and hence, their safety in treatment of serious infections. FDA plans to partner with and obtain input from others, including other Federal agencies, professional groups and the pharmaceutical industry, in order to assure that important antibiotics are used as wisely as possible.

The development of appropriate public health strategies for managing antimicrobial resistance will require more than sporadic and ad hoc data on the occurrence of resistance. A comprehensive system of antimicrobial resistance surveillance is needed to provide a measure of the resistance patterns, an early warning system for emerging problems, and a baseline to target and evaluate prevention control measures. In addition to establishing baselines and showing trends, early warning of an emerging problem may alert clinicians to a possible problem and have an immediate impact on prescribing decisions and outcome for the patient. There is also a need to improve the understanding of the relationship between drug use and resistance in order to use drugs wisely. This need is pressing with regard to both human and food animal antibiotic use. Again, FDA has important partnerships with CDC and U.S. Department of Agriculture (USDA) addressing surveillance and we are committed to continuing these efforts and broadening our efforts as we consider use issues.

FACILITATING PRODUCT DEVELOPMENT

There is and will be a critical need for innovative product development to meet the threat posed by antimicrobial organisms. Desired products include not only new antibiotics, but also vaccines to prevent infections and reduce antibiotic use. We also need improved, more rapid, diagnostics to identify pathogens and drug resistance. At each step of the product development process, there is room for improvement and innovation.

As we address this matter we also need to acknowledge that each new antimicrobial agent represents a major investment by a pharmaceutical company, which must shepherd the product through pre-clinical studies and clinical testing. As is stated in a recent World Health Organization (WHO) report, few breakthroughs in the discovery of antimicrobials have been accidental discoveries, stumbled upon by chance. Instead, they are the result of dedicated scientific effort and vast amounts of money, time, and human labor. This is also true of the development of novel new treatments and of vaccines.

FDA and its partners will continue to consult with representatives of the pharmaceutical industry and other expert parties, such as FDA's Advisory Committee on Anti-Infective Drugs, on strategies to promote the development of new antimicrobial drugs, vaccines, and diagnostic tests. We need to collectively address overcoming economic disincentives to new antimicrobial product development and renewed efforts to promote and expect appropriate use of these important products.

Some examples of what we are doing to facilitate product development for drugs, vaccines, and medical devices follow.

Drugs

During July 1998, FDA's Center for Drug Evaluation and Research (CDER) sponsored a public meeting with industry, academia and other public health agencies to receive input on the topic of antibiotic resistance. This meeting was followed in October 1998, by an Advisory Committee meeting to discuss the issues raised at the July meeting, and included: ways to help speed product development, including approaches to improve clinical trials for studying drugs targeted at resistant organisms; programs that may provide incentives for drug development, such as Orphan Drug designation; and approaches to promote the appropriate use of antibiotics.

As I stated previously, to provide therapeutic options for the treatment of infections due to resistant organisms, critical antibiotics need to be brought to market as expeditiously as possible. The Agency is granting these applications a priority review, which ensures that these applications are acted on in six months or less. Shortening the development time of these products is also important in bringing these products to market as soon as possible. In this regard, the Agency has worked with sponsors of these products though early discussions on overall product development, clinical trial design, and other issues that may arise so that the process can be as efficient as possible and provide the data that would be necessary to determine the safety and effectiveness of the product. In addition, the use of regulatory approaches to provide more rapid development, such as early consultation and early access (Subpart E designation), and accelerated approval utilizing a surrogate endpoint (Subpart H), has also been discussed.

Two of the most recent approvals for products to treat highly resistant organisms - Synercid® and Zyvox® - were developed and reviewed using these approaches. Prior to the approval of these products, patients who were infected with vancomycin-resistant enterococci had no other available therapies. Many of these patients are immunocompromised or have serious underlying illness requiring care in an intensive care unit and are therefore the most vulnerable. These products are truly "live saving" for these patients.

The development of innovative new products to treat infections due to resistant organisms, especially those for which there are few treatment options, such as multiple resistant gram negative or gram positive organisms, is critically important. CDER has taken the initiative in developing policies regarding the development and the appropriate use of drugs of last resort. This will include developing recommendations that focus the development of these products on the area of need, guidance on the design of clinical trials for these products, the application of regulatory approaches, such as accelerated approval, and the development of policies that will promote the appropriate use of these products. There are a number of issues that will require further refinement and resolution. At present, antibiotics are usually developed for a number of indications (diseases) caused by a variety of organisms, including organisms resistant to other antibiotics. This provides a potentially large market for the sponsor to recoup their research and development costs. This is not a good approach if one wishes to preserve antibiotics that treat resistant organisms. However, the numbers of patients infected with resistant organisms may be sufficiently limited to discourage drug development only for this population. Strategies to overcome these potential economic disincentives to development and to appropriate use will also be considered. The application of existing programs, such as Orphan Drug designation, has been discussed as one potential approach at public meetings in July and October, 1998.

Vaccines

The Agency also is encouraging the development of new vaccines to help reduce the need for antibiotics and, thus, slow the spread of resistance. Pointing to the global importance of vaccines, the WHO refers to prevention through vaccination as the ultimate weapon against infection and drug resistance.

An important vaccine for the prevention of meningitis (a severe infection of the lining of the brain or spinal cord) occurred earlier in the decade. Before the approval of the first Haemophilus influenzae type b (Hib) vaccine in 1990 for infants, Hib was the leading cause of bacterial meningitis and was becoming increasingly antibiotic resistant. Today, invasive Hib infection has been virtually eliminated from the U.S. by effective vaccines, reducing not only harm to children but also antibiotic use.

Earlier this year, FDA approved the first vaccine to prevent invasive pneumococcal diseases in infants and children, Prevnar. This vaccine prevents invasive diseases caused by the organism Streptococcus pneumoniae, including bacteremia (an infection of the bloodstream) and meningitis, a severe infection of the lining of the brain or spinal cord.  Streptococcus pneumoniae remains as one of the leading causes of bacterial meningitis, and we are hopeful that vaccines like Prevnar will greatly reduce this threat.

This new vaccine is great news for parents and their children because now, we have a highly effective way to prevent pneumococcal infection, now the major cause of meningitis and serious blood infections in the most susceptible children - those under two years of age.

In addition, pneumococcal vaccines are being studied for the prevention of otitis media and pneumonia, which are often due to pneumocci. The potential contribution of pneumococcal vaccines in helping to reduce these diseases could further reduce the use of antimicrobials. Numerous other promising vaccine candidates to protect against organisms for which antimicrobials are typically administered are in various stages of clinical development.

In addition to vaccines that directly impact on pathogens with recognized high rates of resistance, vaccines are also under development that would indirectly affect antimicrobial use. For example, ear infections and respiratory diseases are often treated with antibiotics, but most are caused by viral infections, such as parainfluenza and respiratory syncytial virus . Therefore, development of vaccines to prevent these viral infections would also be an important mechanism impacting on unneeded and nonbeneficial antibiotic use.

FDA's Center for Biologics Evaluation and Research (CBER) recognizes the importance of expediting clinical development of these products and their public health benefit. CBER has worked with academia, manufacturers, and other government agencies to address the development of new vaccines and therapies as alternative approaches to reduce antimicrobial use. For example, CBER has participated in several workshops addressing key issues related to the development of combination vaccines against multiple childhood diseases. In addition, CBER has expedited the clinical development and approval of these products. For example, through the provisions provided by FDAMA, Prevnar was granted fast track designation and assigned priority review status.

Devices

Another product line that we want to facilitate that will have a significant impact on the appropriate use of antimicrobials is the development of new diagnostic tests that can rapidly determine and certainly indicate whether an infection is bacterial. The test would also then be expected to identify an appropriate antibiotic for treatment. Diagnostic tests that are reliable and whose results are more quickly available have great potential for reducing prescription of antibiotics when they are not necessary and over prescribing a more powerful antibiotic than is clinically necessary. Conversely, rapid identification of resistant infections can lead to earlier use of effective treatments and better outcomes for patients. FDA's Center for Devices and Radiological Health (CDRH) reviews these types of products premarket, assuring that expected performance is reliable for use in patient management and gathering data for surveillance.

FACILITATING SAFE AND EFFECTIVE USE OF ANTIMICROBIALS

As I stated, antimicrobial resistance is an inevitable consequence of the selective pressure of widespread and often inappropriate antimicrobial use. We all --physicians, patients, pharmaceutical companies, public health professionals, and government agencies -- must concede the fact that individually and collectively we are a part of the problem, and acknowledge that it will take all of our efforts to arrive at the solution.

The medical profession plays an important role in this issue. Physicians tell us that patients often pressure them to prescribe antibiotics. They may have limited time to explain the rationale for not using an antibiotic, or for using an alternative treatment. They may not have access to rapid diagnostic tests or to antibiotic sensitivity testing. In addition, there may be financial disincentives to perform these tests. It can be far too tempting to simply prescribe an antibiotic. Since this is often a shot in the dark, because the bacteria have not been identified and susceptibility testing not done, the physician is further tempted to prescribe the latest powerful blockbuster antibiotic. Such antibiotics are often not warranted, as many community acquired infections are viral and do not respond to antibiotics or are caused by bacteria still sensitive to older alternative drugs.

A colleague of mine told an interesting story. She was waiting in line at the pharmacy in a hospital in the Washington area. This was just outside the outpatient surgery area. She was the fifth person in line. Now this was shortly after a particular fluoroquinolone was approved. I will not mention the name of the product. The point is that, believe it or not, every single person in the line in front of her was given this new fluoroquinolone. And so was she. It was the blockbuster antibiotic of the day. One might conclude that it was being pushed a little too hard and perhaps used when it was not necessary.

Once an antibiotic is prescribed a lack of patient understanding and, therefore, compliance may also contribute to resistance. Patients, either by omission or commission, often do not take the antibiotic according to directions, and frequently fail to take the entire course of antibiotics. Instead, they stop taking it when they feel better, and then save the rest for the next time or share the leftover drug with a sick friend. The result, inadequate treatment courses, also is a recipe for inducing resistance.

It is not easy to accurately establish the extent of overuse or inappropriate use of antibiotics by the medical profession or patients, but several studies have given estimates that present a picture of substantial overuse of these products. Office-based physicians in the U.S. write more than 100 million antibiotic prescriptions each year. According to CDC, perhaps as many as half of those prescriptions--a total of 50 million--may be unnecessary. They are prescribed for patients who have the common cold and other viral infections, including influenza.

I would like to recognize here the encouraging report last week from CDC that showed that the rate of prescriptions written for children with respiratory illnesses declined between 1989-1990 and 1997-1998. Hopefully, this study is an indication that antibiotics are being used more wisely.

A third component that contributes to antibiotic resistance is the marketing practices of pharmaceutical companies. The messages conveyed are naturally geared to persuading health professionals to buy and use their products. With well over 80,000 detail people and active direct to consumer advertising campaigns, there are effective means to get any marketing message out. An article in USA Today commented that, "Physicians must be honest with themselves and with their patients. Decisions on which prescriptions to write must be made in accordance with the best scientific evidence, not on the best marketing campaign."

However, we have also been remiss at the Federal, State, and Local levels in not aggressively getting out the message about the importance of appropriate antibiotic use and the need to protect these resources.

We need to educate physicians and the public about the resistance problem and encourage more judicious use of antimicrobial drugs. We pledge to do our share with both industry and other public health officials, to provide better and more consistent information to consumers and health care professionals. We believe it is particularly important to include additional information in the labeling of prescription antibiotics.

Yesterday, FDA proposed a regulation that will require statements on prescription antibiotic drug labeling that discuss the appropriate use of antibiotics and how to reduce the development of drug-resistant microorganisms. The proposal is intended to encourage physicians to prescribe systemic antibacterials more judiciously and only when clinically necessary. The proposal also is intended to encourage physicians to counsel their patients about the proper use of such drugs and the importance of taking them as directed.

Specifically, the proposed rule would require that:

  • "… at the beginning of the label, under the product name, the labeling must state that inappropriate use may increase the prevalence of drug resistant microorganisms and may decrease the effectiveness of the drug product and related antimicrobial agents, and that the drug product should be used only to treat infections that are proven or strongly suspected to be caused by susceptible microorganisms;
  • the 'Clinical Pharmacology' section state that appropriate use of the drug product includes, where applicable, identification of the causative microorganism and determination of its susceptibility profile;
  • the 'Indications and Usage' section state that local epidemiology and susceptibility patterns of the listed microorganisms should direct initial selection of the drug product for the treatment of the listed indications and that because of changing susceptibility patterns, definitive therapy should be guided by the results of susceptibility testing of the isolated pathogens;
  • the 'Precautions' subsection entitled 'General' state that inappropriate use may increase the prevalence of drug resistant microorganisms and may decrease the future effectiveness of the drug product and related antimicrobial agents. This subsection would also include a statement that the drug product should only be used to treat infections that are proven or strongly suspected to be caused by susceptible microorganisms; and,
  • the 'Precautions subsection entitled 'Information for Patients' state that patients should be counseled that the drug product should be used only to treat bacterial infections and that it does not treat viral infections. The subsection would also advise physicians to counsel patients that the medication should be taken exactly as directed."

The recently approved antimicrobial, Zyvox® (linezolid), has some of this language in its package labeling. Under Indications and Usage, the labeling states, "Due to concerns about inappropriate use of antibiotics leading to an increase in resistant organisms, prescribers should carefully consider alternatives before initiating treatment with Zyvox® in the outpatient setting."

It goes on to say, "Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify the causative organisms and to determine their susceptibility to linezolid [Zyvox®]. Therapy may be instituted empirically while awaiting the results of these tests. Once these results become available, antimicrobial therapy should be adjusted accordingly." The Agency also has issued a request to the sponsor of another drug of last resort asking that they include a statement in the package insert regarding the appropriate use of their product. Discussions with the firm are ongoing.

We believe that having more of this type of information on product labeling will influence prescribing behavior, and that the Zyvox® labeling is a step in the right direction and we applaud Pharmacia and Upjohn for working with the Agency to develop this message.

COORDINATING FDA's SCIENTIFIC RESPONSE TO ANTIMICROBIAL RESISTANCE

Lastly, research is an important FDA activity in supporting and filling gaps in the science base of the Agency. Basic and applied research provide the foundation for combating the problem of antimicrobial resistance. Research is essential to support the development of new antimicrobial drugs, vaccines, and diagnostic tests and the development of innovative uses of products. Research also plays an essential role in supporting the science base for regulatory structures and decisions.

Although NIH is the lead government agency focusing on research associated with antimicrobial resistance, FDA research supports strategic goals, such as the development of knowledge bases, and method, agent, or concept driven research. FDA has important scientific resources invested in antimicrobial research and related areas and FDA scientists have made important contributions to the field. The spectrum of such research ranges from the basic, such as mechanisms of resistance induction and transfer related to food animal use of antimicrobials, to the applied, such as improved detection of resistant pathogens in regulated food products.

CVM's FRAMEWORK DOCUMENT

Let me next briefly address our effort in the area of antimicrobial use in food-producing animals - an area of controversy that has spanned the past 30 years. Antibiotics have, for decades, played a key role in ensuring the health of food animals. And, as you know, producers have used some of these same products as growth promoters. Such uses contribute to the general availability of safe food products at reasonable prices. At the same time, the potential risks posed by antimicrobial resistance have become of increasing concern.

In response, FDA developed in 1999 a discussion document entitled "A Proposed Framework for Evaluating and Assuring the Human Safety of the Microbial Effects of Antimicrobial New Animal Drugs Intended for Use in Food-Producing Animals."

The proposed Framework describes the Agency's best thinking on how to evaluate the microbial safety of antimicrobials for use in food animals. The concepts described in the Framework could be used to assess not only new antibiotics, but also previously approved antibiotics. The Agency will take appropriate procedural steps to develop and implement any policies resulting from the concepts.

We believe that the proposed Framework presents a sound science and risk-based approach to the antimicrobial resistance issue, and consistent with guidance issued in December 1999, we are asking companies to assess the microbial safety of all new antimicrobials to be used in food animals.

Depending on the results of this assessment, the drug sponsor may need to conduct pre-approval studies to assess the rate and extent of resistance development in pathogens or commensals of human health concern. We will be issuing a guidance document in the near future to more specifically outline how such studies can be conducted. In addition, we will hold a scientific workshop in January 2001, to outline our approach and seek public input on the establishment of resistance and monitoring thresholds. I would also like to note that the veterinary medical profession and specialty practice organizations of veterinary practitioners are developing judicious use guidelines as well.

As the mechanism for regulating these drugs, the proposed Framework discusses three categories of antimicrobial drugs. The categories would be based on the drug's unique or relative importance to human medicine.

The chain of events that leads to the transfer of antimicrobial resistance from animals to humans is complex. It includes the ability of the drug to induce resistance in bacteria, and the likelihood that use of the drug in food-producing animals will promote resistance. It also includes the likelihood that any resistant bacteria in or on the animal will then be transferred to humans. The final link in this chain of events is the likelihood that such transfer will result in loss of efficacy of human antimicrobial therapies.

The proposed Framework also includes a characterization of the likelihood of human exposure to resistant, foodborne pathogens as HIGH, MEDIUM or LOW. To do this, the drug's attributes--for example, its mechanism and rate of resistance induction, and its induction of cross-resistance to other related or unrelated drugs--would be considered. The proposed Framework also includes an evaluation of how the product is used, and other relevant factors such as animal and manure management practices, environmental contamination, and food processing.

The extent of data required before and after approval of a new antimicrobial drug would depend upon a consideration of the drugs importance to human medicine, the potential for human exposure, and other factors as they may be deemed relevant.

The need for FDA to have additional and more detailed animal drug distribution information is also discussed in the proposed Framework. This information would be most useful if it could be reported by state, species, dosage form, season of use, and an estimate of the antimicrobial activity units sold. Implementation of the concepts articulated in the Framework document would be presented to the public through guidance or notice and comment rulemaking, as appropriate.

National Antimicrobial Resistance Monitoring System: Enteric Bacteria

To make this Framework operational we will depend upon an effective resistance surveillance system and scientifically sound risk assessments. We can now obtain valuable resistance data through the National Antimicrobial Resistance Monitoring System: Enteric Bacteria (NARMS). FDA proposed NARMS in 1995 in response to growing concern about the emergence of untreatable antimicrobial resistance. NARMS was developed in 1996 as a collaborative surveillance effort by FDA's CVM, CDC, and the USDA. This system allows us to prospectively monitor changes in the antimicrobial susceptibility of selected zoonotic, enteric pathogens and commensals.

Currently, NARMS monitors the susceptibility of Salmonella and E. coli to 17 antimicrobial drugs, including ciprofloxacin, ceftriaxone, ceftiofur, tetracycline, and others. NARMS also monitors susceptibility of Campylobacter isolates to eight antimicrobial drugs-among them--azithromycin, ciprofloxacin, clindamycin, erythromycin, and tetracyline.

Seventeen State and Local Health departments submit human clinical isolates of non-typhoid Salmonella and E. coli. Eight State health departments submit human clinical Campylobacter isolates. And four States submit Campylobacter isolates from retail poultry. In 1998, NARMS was expanded to include sentinal sites at veterinary diagnostic laboratories.

USDA conducts animal isolate testing which is done at their Agricultural Research Service Russell Research Center. And CDC conducts testing on human isolates at their National Center for Infectious Diseases Foodborne Disease Laboratory.

NARMS is proving to be a valuable source of resistance data, and is helping us characterize the scope of the resistance issue, and monitor changes. NARMS serves as a model surveillance system for other nations establishing their own surveillance systems.

Risk Assessment

Last December, FDA released a draft quantitative risk assessment that modeled the human health impact of fluoroquinolone-resistant Campylobacter infections associated with the consumption of chicken. We used data from NARMS, CDC's case control studies, FoodNet, and other sources, for the risk assessment. We'll finalize the results of the risk assessment by early this fall, but the preliminary results did indicate that there is an impact on human health from fluoroquinolone-resistant Campylobacter associated with chicken consumption.

And we have initiated a second risk assessment. We are currently conducting a feasibility study to determine whether sufficient data can be obtained to complete a quantitative risk assessment. This one will assess the plausibility of a link between the use of virginiamycin in animals and quinupristin/dalfopristin resistance in humans as well as the human health impact attributable to use of virginiamycin in food-producing animals. This risk assessment will also evaluate risk management options to address the human health impact if it is deemed unacceptable. Ultimately, we want to ensure that significant human antimicrobial therapies are not compromised or lost due to antimicrobial use in animals. At the same time, we want to provide for the use of safe and effective antimicrobials in food animals.

The other major issue related to the use of antimicrobials in food-producing animals is their use for growth promotion in livestock. The Framework approach could also be applied to these products and we will focus our efforts on evaluating those uses that pose the greatest risk to public health. As in all of our decision-making, the best available science will be used to ground and guide our actions.

Antimicrobial Resistance and the Budget

Mr. Chairman, I would be remiss if I did not take this opportunity to thank you for approving FDA's antimicrobial resistance increase request in the FY 2001 Senate Appropriations bill. Both the Senate and the House bills as passed include full funding of FDA's request for antimicrobial resources. The FY 2001 request builds upon three years of intense work and cooperation among several key agencies, FDA, CDC, NIH, USDA and several State and Local Health agencies. FDA believes Congressional funding of the Food Safety Initiative has served a key role in establishing a coordinated approach to food safety and antimicrobial resistance. We expect funding for antimicrobial resistance to be a continuing priority.

INTERAGENCY TASK FORCE ON ANTIMICROBIAL RESISTANCE

As I mentioned above, FDA recognizes that managing antimicrobial resistance requires coordinated actions and partnerships with many other entities, both within and outside the Federal government. FDA co-chairs with CDC and NIH an Interagency Task Force on Antimicrobial Resistance that was formed in 1999 to develop a Public Health Action Plan to Combat Antimicrobial Resistance.

The Public Health Action Plan reflects a broad-based consensus of Federal agencies on actions to combat antimicrobial resistance and provides a blueprint for specific, coordinated Federal actions. A draft Part I of the Action Plan focusing on domestic issues was published in late June of this year. Part I includes many proposed activities which FDA will address either as a coordinator or as a partner with other agencies, including priority items to foster product development, to educate professionals and the public, and to develop and implement the concepts outlined in the CVM Framework. Part II of the plan, to be developed subsequently, will follow development of WHO's approach and identify U.S. agency actions that can more specifically help address international issues. Development and implementation of the Public Health Action Plan also has included and will continue to include the participation and efforts of the Agency for Healthcare Research and Quality, USDA, the Department of Defense, the Department of Veteran Affairs, the Environmental Protection Agency, the Health Care Financing Administration, and the Health Resources and Services Administration. These partners are critical given the complex nature of resistance and the need to address the issue in an inclusive and coordinated manner, with consideration of such diverse areas as health care systems, the environment, and agriculture.

CONCLUSION

Let me once again underscore that to adequately address this public health issue, it will take responsible action by more than just Federal agencies. It is going to take energy and determination on the part of the medical and veterinary professions, the pharmaceutical and animal health industries, and those who grow and care for food-producing animals.

Our highest priority should be to ensure that we have safe and effective antimicrobials to protect human and animal health today and in the future. FDA is committed to doing our part to ensure that this happens. We feel that the internal FDA Task Force Plan and the Interagency Public Health Action Plan are important blueprints to move us forward in a coordinated and effective way.

I would be happy to answer any questions you may have.


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