Battle of the Bugs: Fighting Antibiotic
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.
Antibiotic resistance, 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.
Although resistant 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 early on."
How Resistance Occurs
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
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 Ear.")
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
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
"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
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.
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)
|Fluid in the Middle
(otitis media with effusion)
Source: Centers for Disease Control and Prevention
Fluid 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
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
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 Resistance
- 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