Medicine’s double-edged sword

Medicine’s double-edged sword – Antibiotics

Mitchel L. Zoler

Since their introduction in the 1940s, antibiotics may have had a greater impact on public health than any other medical discovery. These agents are the only twentieth-century innovation that experts credit with extending the life span of the average American by as much as ten years.

The first antibiotics were chemicals that microorganisms such as bacteria and fungi used to kill enemy bacteria and other minuscule attackers. These substances are valuable as drugs because they can combat human infections caused by the same organisms. Today, the antibiotic label is also affixed to synthetic versions of these naturally occurring compounds. Laboratory scientists have cooked up many hundreds of such drugs over the years, and more than 100 have been tested and approved for treating infections. The list is subdivided into “families” of agents that resemble each other in chemical structure or mechanism of action.

Antibiotics are both highly effective and widely used. Infections rank among the top three reasons why people seek care from a physician, and when the illness is caused by bacteria the patient is very likely to leave the office with an antibiotic prescription in hand. But antibiotics are not panaceas: they can’t do their job unless taken according to instructions, they can interact with foods or other drugs, and they have unpleasant and even dangerous effects in some people.

Pragmatic prescribing

When an antibiotic is called for, doctors rely on a combination of experience and judgment in deciding which one to use. For a relatively mild infection that won’t require hospitalization, physicians generally don’t go to the time and expense of trying to pin down exactly what organism is to blame. Instead, they select an antibiotic based entirely on the patient’s signs, symptoms, and medical history.

One notable exception is the combination of a fever and an inflamed sore throat. In this case, physicians usually swab the patient’s throat and test for Group A Streptococcus- the cause of what’s commonly known as “strep throat.” If this bacterium is present, an antibiotic such as penicillin is almost sure to clear up the infection. But if no strep is found and the illness is viral, antibiotics are worthless.

“The most common misuse of antibiotics is when they are employed to treat viral infections,” noted pharmacist Steven Barriere, a specialist in infectious diseases at the University of California, Los Angeles. When people take drugs that are powerless to combat what ails them, they are subjected to unwarranted costs and adverse effects.

Nevertheless, some physicians find themselves prescribing antibiotics for viral infections simply because “patients often have a strong expectation that when they see a doctor for an infection, they should come away with a drug prescription,” noted Richard Platt, an associate professor of medicine at Harvard Medical School. Patients can reduce their exposure to unnecessary drugs by not insisting that they be prescribed for every little illness.

When an infection is serious enough to require hospitalization, physicians put considerably more emphasis on identifying the critter that’s to blame. Although doctors typically prescribe an antibiotic fight away, they first collect an appropriate specimen to send to a laboratory where the offending microorganism can be identified. Once the pathogen is known, the patient may need to switch antibiotics if a different agent is clearly a better match for the bug.

Use as directed

Even when the right antibiotic is used, results often fall short of expectations if patients unwittingly sabotage their own treatment. To begin with, medications won’t do much good if they’re not taken or if they’re used on the wrong schedule. “A lot of data show that as soon as patients feel better, they stop taking their drug,” observed Dr. Platt. As a result, some bacteria survive and the therapy appears not to work. And the plot thickens if people salt away the remaining pills for future use.

“A common scenario is the patient with a sore throat who’s been prescribed penicillin in case it is a strep infection,” said Cyrus C. Hopkins, clinical director of the infectious diseases unit at the Massachusetts General Hospital. “The symptoms disappear after three days, so he or she stops taking the drug. Three months later the patient has another sore throat and takes the penicillin for another three days until the symptoms disappear. This happens again a few months later. Finally, the patient develops a more serious infection, a pneumonia, due to a drug-resistant bacterium that is hard to treat.”

Drug-resistant strains can spring up when a population of microorganisms is repeatedly exposed to the same antibiotic. In mammals thousands of years are required for a specific adaptation (such as a sharper incisor or a broader hoof) to evolve, but bacteria can acquire the ability to shrug off a drug in a matter of months. This is explained partly by their brief life cycle (some mature and produce progeny in as little as 20 minutes), as well as by their ability to perform genetic tricks such as acquiring DNA from an unrelated species of bacterium.

Drug resistance is less likely to evolve in the face of older antibiotics with a narrow spectrum of activity than with exposure to more-general agents. Several newer antibiotic families, including quinolones and cephalosporins, combat a much broader range of bacterial types than old standbys like penicillin and erythromycin do. And the more microorganisms that are affected, the greater the chance that a resistant strain will evolve. Although the costly, broader-spectrum agents should be reserved for infections that don’t respond to more-traditional drugs, some doctors use them inappropriately because they are new, heavily promoted, and powerful.

No free lunch

People can further increase the likelihood that antibiotics will do what they’re supposed to by following the instructions spelled out on the pharmacy label. Many of these guidelines are aimed at preventing untoward interactions between the antibiotics and either foods or other drugs.

Tetracyclines and quinolones, for example, should not be taken with dairy products, antacids, or iron supplements, which can block their absorption from the digestive tract into the bloodstream. (For more information about drug-food interactions, see the Harvard Health Letter, January 1993.) Some such drugs also induce temporary photosensitivity, which can lead to a sunburnlike rash.

In addition, trouble can arise from interactions between antibiotics and other medications. Erythromycin, for example, inhibits production of liver enzymes that are needed to metabolize certain other drugs. Without enough of these key enzymes, dangerously high levels of such agents can accumulate in the blood. Drugs that should generally not be taken concurrently with erythromycin include the antiseizure medication phenytoin and the asthma remedy theophylline. (If you take one of these agents, be sure to tell any doctor who prescribes an antibiotic for you. ) Last summer it became clear that two new antihistamines, Seldane and Hismanal, also interact badly with erythromycin. In rare cases this interaction has led to cardiac arrest and death. (See the Harvard Health Letter, November 1992.)

Trade-offs

Sometimes antibiotics cause adverse effects in people who have followed instructions to the letter. Gastrointestinal distress is the most common and may take the form of indigestion, abdominal pain, nausea, vomiting, and diarrhea or other changes in bowel habits. Although any antibiotic is capable of producing these effects in some individuals, erythromycin is in a class by itself: some studies indicate that it brings on gut problems in as many as 40% of users.

One way to reduce the ill effects is to take erythromycin or other troublesome antibiotics on a full stomach, said UCLA’s Dr. Barriere. However, this strategy may reduce the amount of medication absorbed from the GI tract into the bloodstream.

As almost every woman knows, the vagina is another body site that is vulnerable to antibiotic-induced disturbances in the native bacterial ecosystem. Protective microbes normally help keep the vagina free of infection by Candida albicans, a yeastlike fungus. For some women even a brief course of antibiotics can lead to a yeast infection. Unfortunately, experts say that there is no sure way for susceptible women to avoid this completely. But they can minimize their risk by starting on antiyeast cream or suppositories as soon as they begin an antibiotic regimen.

Some people are allergic to certain antibiotics, and in a few cases their reactions can even be lethal. Penicillin and its relatives are the most common triggers for an allergic response, but in many cases a suspected allergy to this drug may not actually be one. Annoying but harmless reactions include GI distress, rash, and fever. More worrisome responses- which occur in about one of every 1,000 penicillin users- include the appearance of hives, difficulty breathing, or swelling of the tongue, mouth, or face right after dosing.

Such serious reactions should be reported to a physician immediately and incorporated into the individual’s medical record, because “the appearance of facial or oral swelling indicates that the patient may develop an anaphylactic response [a life-threatening type of allergic reaction] to the next dose of the drug,” Dr. Hopkins said. Fortunately, a combination of skin testing and a careful medical history can be used to predict the likelihood of a severe reaction if penicillin is needed in the future.

In the final analysis, antibiotics clearly have blunted the effects of infectious diseases that once laid low or even killed countless thousands of people. However, prudence dictates that they–like all powerful weapons–be handled with care.

Drugs of Choice

Condition Recommended Antibiotics*

Uncomplicated bacterial pneumonia Penicillin, ampicillin, or

erythromycin

Acute bacterial bronchitis Erythromycin, amoxicillin,

or ampicillin

Streptococcal skin infections Penicillin

Staphylococcal skin infections Erythromycin or dicloxacillin

Urinary tract infections Ampicillin, amoxicillin, or

trimethoprim/sulfamethoxazole

Otitis media Amoxicillin; for stubborn

cases, ceflaclor,

erythromycin-sulfisoxazole,

trimethoprim/sulfamethoxazole,

or amoxicillin/clavulinic

acid

* These drugs are widely accepted as safe, effective, and

reasonably priced treatments for the conditions listed. Because

individual tolerances vary, however, physicians may substitute

other agents.

COPYRIGHT 1993 Copyright by President and Fellows of Harvard College. All Rights Reserved

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