Linda Bren is a staff writer for FDA Consumer.
Antibiotics are medications with the capacity to destroy disease-causing bacteria. Antibiotic-resistant bacteria have been appearing since the advent of these so-called miracle drugs fifty years ago, but in the past ten years the number of resistant bacteria has increased. While bacteria can develop resistance naturally, they often become resistant in response to antibiotics that are overused by patients and physicians. Doctors cite a number of reasons for overprescribing these drugs, including pressure from patients who show no signs of bacterial infection. The Food and Drug Administration (FDA) is focusing on two methods for lessening the potential danger of antibiotic resistance: encouraging doctors and their patients to use antibiotics with greater care and caution and promoting the development of newer, stronger antibiotics.
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.
Bacteria Are Developing Resistance
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." ...
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.
According to the CDC, antibiotic prescribing ... could be reduced by more than 30 percent without adversely affecting patient health.
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....
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....
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.
Antibiotic Resistance Campaigns
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."
The FDA published a final rule in February 2003 ... to encourage doctors to prescribe [antibiotics] only when truly necessary.
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 [the FDA's Mark] 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.