Battle of the Bugs:
Fighting Antibiotic Resistance
By Linda Bren
Ever since antibiotics
became widely available about 50 years ago, they have been hailed as miracle
drugs--magic bullets able to destroy disease-causing bacteria.
But with each passing
decade, bacteria that resist not only single, but multiple, antibiotics--making
some diseases particularly hard to control--have become increasingly widespread.
In fact, according to the Centers for Disease Control and Prevention (CDC),
virtually all significant bacterial infections in the world are becoming
resistant to the antibiotic treatment of choice. For some of us, bacterial
resistance could mean more visits to the doctor, a lengthier illness,
and possibly more toxic drugs. For others, it could mean death. The CDC
estimates that each year, nearly 2 million people in the United States
acquire an infection while in a hospital, resulting in 90,000 deaths.
More than 70 percent of the bacteria that cause these infections are resistant
to at least one of the antibiotics commonly used to treat them.
also known as antimicrobial resistance, is not a new phenomenon. Just
a few years after the first antibiotic, penicillin, became widely used
in the late 1940s, penicillin-resistant infections emerged that were caused
by the bacterium Staphylococcus aureus (S. aureus). These "staph"
infections range from urinary tract infections to bacterial pneumonia.
Methicillin, one of the strongest in the arsenal of drugs to treat staph
infections, is no longer effective against some strains of S. aureus.
Vancomycin, which is the most lethal drug against these resistant pathogens,
may be in danger of losing its effectiveness; recently, some strains of
S. aureus that are resistant to vancomycin have been reported.
bacteria have been around a long time, the scenario today is different
from even just 10 years ago, says Stuart Levy, M.D., president of the
Alliance for the Prudent Use of Antibiotics. "The number of bacteria resistant
to many different antibiotics has increased, in many cases, tenfold or
more. Even new drugs that have been approved are confronting resistance,
fortunately in small amounts, but we have to be careful how they're used.
If used for extended periods of time, they too risk becoming ineffective
Bacteria, which are organisms so small
that they are not visible to the naked eye, live all around us--in drinking
water, food, soil, plants, animals, and in humans. Most bacteria do not
harm us, and some are even useful because they can help us digest food.
But many bacteria are capable of causing severe infections.
The ability of antibiotics to stop an
infection depends on killing or halting the growth of harmful bacteria.
But some bacteria resist the effects of drugs and multiply and spread.
Some bacteria have developed resistance
to antibiotics naturally, long before the development of commercial antibiotics.
After testing bacteria found in an arctic glacier and estimated to be
over 2,000 years old, scientists found several of them to be resistant
against some antibiotics, most likely indicating naturally occurring resistance.
If they are not naturally resistant,
bacteria can become resistant to drugs in a number of ways. They may develop
resistance to certain drugs spontaneously through mutation. Mutations
are changes that occur in the genetic material, or DNA, of the bacteria.
These changes allow the bacteria to fight or inactivate the antibiotic.
Bacteria also can acquire resistant
genes through exchanging genes with other bacteria. "Think of it as bacterial
sex," says David White, Ph.D., a microbiologist in the Food and Drug Administration's
Center for Veterinary Medicine. "It's a simple form of mating that allows
bacteria to transfer genetic material." The bacteria reproduce rapidly,
allowing resistant traits to quickly spread to future generations of bacteria.
"The bacteria don't care what other bacteria they're giving their genes
to," says White. This means that resistance can spread from one species
of bacteria to other species, enabling them to develop multiple resistance
to different classes of antibiotics.
In 1999, 10 federal agencies and departments,
led by the Department of Health and Human Services, formed a task force
to tackle the problem of antimicrobial resistance. Co-chaired by the CDC,
the FDA, and the National Institutes of Health, the task force issued
a plan of action in 2001. Task force agencies continue to accomplish the
activities set forth in the plan. The success of the plan--known as the
Public Health Action Plan to Combat Antimicrobial Resistance--depends
on the cooperation of many entities, such as state and local health agencies,
universities, professional societies, pharmaceutical companies, health-care
professionals, agricultural producers, and the public.
All of these groups must work together
if the antibiotic resistance problem is to be remedied, says Mark Goldberger,
M.D., director of the FDA's office responsible for reviewing antibiotic
drugs. "This is a very serious problem. We need to do two things: facilitate
the development of new antimicrobial therapy while at the same time preserve
the usefulness of current and new drugs."
Preserving Antibiotics' Usefulness
Two main types of germs--bacteria and
viruses--cause most infections, according to the CDC. But while antibiotics
can kill bacteria, they do not work against viruses--and it is viruses
that cause colds, the flu, and most sore throats. In fact, only 15 percent
of sore throats are caused by the bacterium Streptococcus, which
results in strep throat. In addition, it is viruses that cause most sinus
infections, coughs, and bronchitis. And fluid in the middle ear, a common
occurrence in children, does not usually warrant treatment with antibiotics
unless there are other symptoms. (See "Fluid in the Middle
Nevertheless, "Every year, tens of millions
of prescriptions for antibiotics are written to treat viral illnesses
for which these antibiotics offer no benefits," says David Bell, M.D.,
the CDC's antimicrobial resistance coordinator. According to the CDC,
antibiotic prescribing in outpatient settings could be reduced by more
than 30 percent without adversely affecting patient health.
Reasons cited by doctors for overprescribing
antibiotics include diagnostic uncertainty, time pressure on physicians,
and patient demand. Physicians are pressured by patients to prescribe
antibiotics, says Bell. "People don't want to miss work, or they have
a sick child who kept the whole family up all night, and they're willing
to try anything that might work." It may be easier for the physician pressed
for time to write a prescription for an antibiotic than it is to explain
why it might be better not to use one.
But by taking an antibiotic, a person
may be doubly harmed, according to Bell. First, it offers no benefit for
viral infections, and second, it increases the chance of a drug-resistant
infection appearing at a later time.
"Antibiotic resistance is not just a
problem for doctors and scientists," says Bell. "Everybody needs to help
deal with this. An important way that people can help directly is to understand
that common illnesses like colds and the flu do not benefit from antibiotics
and to not request them to treat these illnesses."
Following the prescription exactly is
also important, says Bell. People should not skip doses or stop taking
an antibiotic as soon as they feel better; they should complete the full
course of the medication. Otherwise, the drug may not kill all the infectious
bacteria, allowing the remaining bacteria to possibly become resistant.
While some antibiotics must be taken
for 10 days or more, others are FDA-approved for a shorter course of treatment.
Some can be taken for as few as three days. "I would prefer the short
course to the long course," says Levy. "Reservoirs of antibiotic resistance
are not being stimulated as much. The shorter the course, theoretically,
the less chance you'll have resistance emerging, and it gives susceptible
strains a better chance to come back."
Another concern to some health experts
is the escalating use of antibacterial soaps, detergents, lotions, and
other household items. "There has never been evidence that they have a
public health benefit," says Levy. "Good soap and water is sufficient
in most cases." Antibacterial products should be reserved for the hospital
setting, for sick people coming home from the hospital, and for those
with compromised immune systems, says Levy.
To decrease both demand and overprescribing,
the FDA and the CDC have launched antibiotic resistance campaigns aimed
at health-care professionals and the public. A nationwide ad campaign
developed by the FDA's Center for Drug Evaluation and Research emphasizes
to health-care professionals the prudent use of antibiotics, and offers
them an educational brochure to distribute to patients.
The FDA published a final rule in February
2003 that requires specific language on human antibiotic labels to encourage
doctors to prescribe them only when truly necessary. The rule also requires
a statement in the labeling encouraging doctors to counsel their patients
about the proper use of these drugs.
Stimulating Drug Development
The FDA is working to encourage the
development of new antibiotics and new classes of antibiotics and other
antimicrobials. "We would like to make it attractive for the development
of new antibiotics, but we'd like people to use them less and only in
the presence of bacterial infection," says Goldberger. This presents a
challenge, he says. "Decreased use may result in sales going down, and
drug companies may feel there are better places to put their resources."
Through such incentives as exclusivity
rights, the FDA hopes to stimulate new antimicrobial drug development.
Exclusivity protects a manufacturer's drug from generic drug competition
for a specific length of time.
The FDA has a variety of existing regulatory
tools to help developers of antimicrobial drugs. One of these is an accelerated
approval process for drugs that treat severely debilitating or life-threatening
diseases and for drugs that show meaningful benefit over existing prescription
drugs to cure a disease.
The FDA is also investigating other
approaches for speeding the antimicrobial approval process. One approach
is to reduce the size of the clinical trial program. "We need to streamline
the review process without compromising safety and effectiveness," says
Goldberger. "One of the things that we are trying to look at now is how
we can substitute quality for quantity in clinical studies." It has been
difficult to test drugs for resistance in people, says Goldberger. "Although
these resistant organisms are a problem, they are still not so common
that it is very easy to accumulate patients."
Scientists and health professionals
are generally in agreement that a way to decrease antibiotic resistance
is through more cautious use of antibiotic drugs and through monitoring
outbreaks of drug-resistant infections.
But research is also critical to help
understand the various mechanisms that pathogens use to evade drugs. Understanding
these mechanisms is important for the design of effective new drugs.
The FDA's National Center for Toxicological
Research (NCTR) is studying the mechanisms of resistance to antibiotic
agents among bacteria from the human gastrointestinal tract, which can
cause serious infections.
In addition, the NCTR has studied the
amount of antibiotic residues that people consume in food from food-producing
animals and the effects of these residues on human intestinal bacteria.
This information led to a new approach for assessing the safety of antibiotic
drug residues in people, which may be adopted by the FDA to help review
drugs for food animals.
To find out more about the broad range
of issues associated with antimicrobial resistance, see the FDA's Web
site at www.fda.gov/oc/opacom/hottopics/anti_resist.html,
and the CDC's Web site at www.cdc.gov/drugresistance/.
Linda Bren is a staff writer for FDA Consumer.
Upper Respiratory Infections and Antibiotics
Most upper respiratory infections are usually
caused by viruses--germs that are not killed by antibiotics. Talk with
your doctor about ways to feel better when you are sick. Ask what you
should look for at home that might mean you are developing another infection
for which antibiotics might be appropriate.
(in otherwise healthy children and adults)
(in otherwise healthy children and adults)
(with green or yellow mucus)
in the Middle Ear
(otitis media with effusion)
Source: Centers for Disease Control
in the Middle Ear
Fluid in the middle ear, also called
otitis media with effusion, is a common condition in children. Fluid often
accumulates in the ear, just like in the nose, when a child has a cold.
In the absence of other symptoms, fluid in the middle ear usually doesn't
bother children, and it almost always goes away on its own without treatment,
says Janice Soreth, M.D., director of the FDA's Division of Anti-Infective
Drug Products. "It usually does not need to be treated with antibiotics
unless it is accompanied by additional signs or symptoms or it lasts a
couple of months."
If your doctor does not prescribe an
antibiotic for your child, do not insist on one. Taking an antibiotic
when it is not necessary can be harmful. It increases the risk of getting
an infection later that antibiotics cannot kill.
Instead, "observe your child," says
Soreth. "If symptoms change, call your doctor to seek further help." Symptoms
to watch for include fever, irritability, decreased appetite, trouble
sleeping, tugging on the ear, or complaints of pain. "If symptoms occur,
it doesn't mean the doctor misdiagnosed the condition," says Soreth. "What
started out as a viral condition may have morphed into a bacterial infection
several days later. If this happens, an antibiotic may be appropriate."
What You Can Do to Help Curb Antibiotic
- Don't demand an antibiotic when your
health-care provider determines one isn't appropriate. Ask about ways
to help relieve your symptoms.
- Never take an antibiotic for a viral
infection such as a cold, a cough, or the flu.
- Take medicine exactly as your health-care
provider prescribes. If he or she prescribes an antibiotic, take it
until it is gone, even if you're feeling better.
- Don't take leftover antibiotics or
antibiotics prescribed for someone else. These antibiotics may not be
appropriate for your current symptoms. Taking the wrong medicine could
delay getting correct treatment and allow bacteria to multiply.
This article originally appeared in
the July-August 2002 FDA Consumer and contains substantial revisions
made in September 2003.