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TESTIMONY
OF
JANE E. HENNEY, M.D.
COMMISSIONER OF FOOD AND DRUGS
FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
BEFORE
SUBCOMMITTEE
ON LABOR, HEALTH AND HUMAN SERVICES
COMMITTEE ON APPROPRIATIONS
SEPTEMBER 20, 2000
RELEASE ONLY UPON DELIVERY
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 will include issues related
to animal drugs and animal health, as resistant organisms
and their genes cross national and regulatory boundaries involving
food, animals, and humans.
The problem of 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. Increased
resistance is an inevitable consequence of the selective pressure
exerted 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 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. Secondly, 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. 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 is 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.
Various Centers within FDA have already been active in addressing
the resistance problem. However, to further stimulate and
coordinate FDA's actions to combat antimicrobial resistance,
in late 1998, an "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.
To this end, 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 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.
1. 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 ACategory
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.1
How antibiotics are used could, as
it has in the past, be regarded as primarily an issue of Amedical
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
sister 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 more wisely, and
this need is pressing with regard to both human and food animal
antibiotic use. Again, FDA has important partnerships with
CDC and USDA addressing surveillance and these efforts should
continue and broaden to consider use issues.
2. Facilitating
Product Development
There will continue to 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, and 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 problem we also
need to recognize 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, followed by expensive clinical trials. 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 an FDA Advisory Committee,
on how to promote the development of new antimicrobial drugs,
vaccines, and diagnostic tests. Strategies to address overcoming
economic disincentives to new antimicrobial product development
and to appropriate use will need development.
Here are some examples of what we are
doing to facilitate product development for drugs, vaccines,
and medical devices.
Drugs
The Center for Drug Evaluation and
Research (CDER) sponsored a public meeting in July 1998 with
industry, academia and other public health agencies to get
input on the problem 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.
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. To that end, 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 critical products is also important in bringing
these products to market as soon as possible. To that end,
the Agency has worked with sponsors of critical 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 B
Synercid_
and Zyvox_
B
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 Alive
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 still require 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 World Health Organization (WHO) refers to prevention
through vaccination as the ultimate weapon against infection
and drug resistance.
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. Meningitis is usually caused by a viral or
bacterial infection. There are different types of bacterial
meningitis. 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 United States by effective
vaccines, reducing not only harm to children but also antibiotic
use. However, 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 B
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 RSV. Therefore, development of vaccines to prevent these
viral infections would also be an important mechanism impacting
on unneeded and nonbeneficial antibiotic use.
The 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 and that will have a significant impact on the
appropriate use of antimicrobials is the development of new
diagnostic tests that can determine rapidly and with certainty
whether an infection is bacterial. If it is, the test will
help 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.
The 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.
3. 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.
First of all, 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 go ahead
and prescribe an antibiotic. And 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 a new and powerful blockbuster antibiotic
that may have the greatest chance of working. Such antibiotics
are often not needed, as many community acquired infections
are viral and do not respond to antibiotics or they 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 the 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, as many as half of those prescriptions--a
total of 50 million--are 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's National Center for
Health Statistics 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 the message of using antibiotics more wisely is reaching
at least some populations.
Adding to the problem are the marketing
practices of pharmaceutical companies, which are often geared
to persuading health professionals to buy and use their products.
And with well over 80,000 detail people and active direct
to consumer advertising campaigns, there are effective
means to get a 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."
Collectively, government agencies at
federal, state, and local levels have not been aggressive
enough in 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. FDA needs to work with industry
and public health officials, using a variety of means, to
provide better and more consistent information to consumers
and health care professionals. To this end of providing better
and more consistent information, we believe it is particularly
important to include additional information in the labeling
of prescription antibiotics.
[The proposed rule is at the
Dept/OMB as of 8/28 B
OP is pushing to get it out in time for the hearing]
Today, FDA is proposing 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:
_ AY
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,
Zyvox7
(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 Zyvox7
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 [Zyvox7].
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 Zyvox7
labeling is a step in the right direction and we applaud Pharmacia
and Upjohn for working with the Agency to develop this message.
4. 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.
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 have
benefits and 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'll be
issuing a guidance document in the near future to more specifically
outline how such studies can be conducted. In addition, we'll
hold a scientific workshop in January 2001 to outline our
approach and seek public input on the establishment of resistance
and monitoring thresholds. I'd also like to note that the
veterinary medical profession and specialty practice organizations
of veterinary practitioners are developing judicious use guidelines
as well.
As a possible workable 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.
As you know, 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
To make this Framework operational
we would 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 (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 Center
for Veterinary Medicine, CDC, and the U.S. Department of Agriculture.
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.
The U.S. Department of Agriculture
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've 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. While this use of antimicrobials
is decreasing, it is still a widespread practice. 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, 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. To this end, 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, the Department of Agriculture, 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 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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