Battle of the Bugs: Fighting Antibiotic Resistance
Ever since antibiotics became widely available about 50 years ago, they have
been hailed as miracle drugs--magic bullets able to destroy disease-causing
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
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 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
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
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 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
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
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 Ear
(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 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
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
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