Overdoing Antibiotics

(This article was first printed in the November 2002 issue of the Harvard Health Letter. For more information or to order, please go to http://www.health.harvard.edu/health.)

Antibiotic resistance is almost as old as antibiotics themselves. Strep infections and gonorrhea quickly became resistant to the sulfa drugs, the first antibiotics. By the early 1950s, already three-quarters of the staph germs isolated from hospitalized patients were resistant to penicillin. The first penicillin-resistant pneumococcal infections—the bacteria that cause earaches in children and pneumonia in adults—emerged in the late 1960s in Australia and New Guinea.

“Little by little we are experiencing the erosion of the strongest bulwarks against serious bacterial infection…” warned Dr. Maxwell Finland, a Harvard infectious disease expert, in a New England Journal of Medicine editorial in 1978.

Dr. Robert C. Moellering, a Harvard Medical School professor, is one of the world’s foremost authorities on antibiotic resistance. When we interviewed him for this article, he echoed Dr. Finland: “What is happening is the continuing erosion of the effect of the currently available drugs.”

It’s a Bad Situation…

So has anything really changed? Yes and no. Clearly the bacterial world never took kindly to our efforts to wipe it out. From the beginning, it thwarted antimicrobial assaults with ruthless Darwinian selection of its most resistant members. Bacteria also evade antibiotics by promiscuously swapping genes within and across species.

But in the past, even worried experts like Finland could take solace from the fact that if one group of antibiotics couldn’t defeat an infection, another probably would: if penicillin didn’t work, methicillin might. Then the macrolides (erythromycin and others) came along, followed by the cephalosporins and the fluoroquinolones like ciprofloxacin, more commonly known by its anthrax-fighting brand name, Cipro.

New antibiotics are still being developed. The FDA has approved Synercid (quinupristin/dalfopristin) and Zyvox (linezolid). But there isn't the old confidence (bordering on hubris) that a new drug will be waiting in the wings to swoop in and succeed after established drugs have failed.

Meanwhile, doctors are seeing more infections resistant to the existing drugs. Vancomycin (pronounced van-koe-MY-sin) is the powerful, last-resort antibiotic given only to hospitalized patients. Vancomycin-resistant enterococci, bacteria that infect wounds and the urinary tract, were reported in the United States in the 1990s. But American health officials were alarmed in 2002 when a Michigan woman developed the first vancomycin-resistant staph infection in the United States. Fortunately, the disease didn’t spread, and the infection turned out to be vulnerable to other antibiotics.

Another reason to worry: the heavy use of antibiotics in livestock farming. In a study published in the Oct. 18, 2001, New England Journal of Medicine , FDA officials reported finding antibiotic-resistant salmonella in ground meat.

…But it Could be Worse

Even as antibiotic-resistant infections become more common, the most serious cases—infections that don’t respond to any drugs—occur primarily among people who either are very sick or have weakened immune systems from transplant surgery or cancer treatment. Moreover, some of the most resistant organisms—Enterococcus faecium, for example—don’t spread easily: antibiotic resistance and contagiousness are not the same thing.

Meanwhile, the message about the dangers of overusing antibiotics seems to be sinking in. In 2002, the New York Times reported that Tyson Foods, Perdue Farms, and Foster Farms promised to cut back on antibiotics in chicken feed. In September of that year, the FDA proposed regulations aimed at reducing the use of antibiotics for all livestock. Doctors have also responded, according to a government study published in the June 19, 2002, Journal of the American Medical Association (JAMA) . It showed that office-based doctors wrote 40% fewer prescriptions for antibiotics for children and adolescents in 1999–2000 than they did ten years earlier.

Hurried Doctors

Doctors prescribe antibiotics for too many patients for several reasons. Physicians strive to avoid the worst case. So for example, they might prescribe antibiotics for young children on the chance that the infection might spread and cause meningitis.

Doctors are also pressed for time. Rather than have a long conversation with a patient explaining why antibiotics aren’t necessary, they just write the prescription. Some doctors practice defensive medicine, calculating that it’s better to give the antibiotics than face a lawsuit for not doing so.

Are You Part of the Problem?

The doctor is the one holding the prescription pad. But a patient can certainly try to pressure his or her doctor into writing a prescription—or shop around for one who will. If you’ve come to expect an antibiotic for a sore throat because you’re worried that it might be strep, or for a bad cold because you’re convinced it is bacterial sinusitis, it’s time to change your thinking. If the arguments about the greater good don’t grab you, then maybe self-interest will. Several studies suggest (granted, proof is a ways off) that if you take antibiotics, your personal risk of infection by a resistant organism increases.

Recognizing that public attitudes play into antibiotic overuse, the federal Centers for Disease Control and Prevention (CDC) kicked off an ad campaign in 2002 to dissuade people from asking for antibiotics when they’re not needed. It remains to be seen how effective it will be. The campaign has a small budget (just $400,000), and CDC officials say the television networks have been “very lukewarm and kind of cold” to donating broadcast time.

Giving doctors other ways to help patients besides reflexively prescribing antibiotics is another way to cut back on overuse. The CDC now has a program in about two dozen states that supplies doctors with “nonprescription prescription pads.” The pads offer tips and sometimes a few items to help patients cope with illnesses that aren’t bacterial and therefore cannot be treated effectively with antibiotics: drink fluids, use cold packs to ease swelling, and take a pain reliever like ibuprofen (Advil, Motrin, other brands).

Solutions: A Few Suggestions

Give doctors guidelines.

Spelling out exactly when antibiotics should be used might help doctors so they don’t have to make case-by-case decisions. According to Dr. Moellering, a Dutch program reduced antibiotic prescriptions because it instructed doctors not to treat earaches in children age two or older with antibiotics for the first 3–4 days of symptoms. They were treated with pain relievers and ear and nose drops instead. In Finland, concern about the emergence of erythromycin-resistant group A streptococcal infections led to policies that cut the use of erythromycin’s class of antibiotics almost in half.

Keep courses short.

The shorter the course of treatment, the less chance of promoting resistant bacteria. A study published in the July 4, 2001, JAMA showed positive results for short-course, high-dose amoxicillin in children (90 milligrams per kilogram (mg/kg) daily for 5 days versus 40 mg/kg daily for 10 days). An uncomplicated urinary tract infection in young women can be treated effectively with three days or less of antibiotics. Traveler’s diarrhea can be cured with a three-day course. But for many infections, there’s a surprising lack of evidence on the optimum treatment schedule. Even if shorter courses were recommended, many people might not tolerate the higher doses of antibiotics that they often require.

Make sure children and everyone 65 or older gets the pneumococcal vaccine.

“Should we use it? Absolutely, unequivocally. But is it the final answer? Probably not,” says Moellering. The vaccine protects against just 23 of the 81 types of pneumococcal bacteria. The good news is that those 23 varieties are ones that most frequently cause severe infections. Moreover, anything that cuts down on the number of pneumococcal infections decreases antibiotic use.

Pinpoint use of antibiotics.

Hospital patients who tell doctors they’re allergic to penicillin are often treated with the more powerful and broad-spectrum antibiotics from the fluoroquinolone class (ciprofloxacin, levofloxacin, ofloxacin, others) or vancomycin. But people are often mistaken about being allergic to penicillin. Moreover, penicillin allergies often fade, so a prior reaction doesn’t necessarily mean that you are currently allergic. Researchers at the Cleveland Clinic studied whether doing skin tests for penicillin allergies would identify patients who were truly allergic. They found that 21 of the 24 patients classified as being allergic were negative on the skin test.

Walling Off Infections

Antibiotic resistance deserves all the attention it’s getting—and then some. On the other hand, super-germ scenarios shouldn’t overshadow the marvelous benefits of antibiotics. Anyone who has seen a child racked by a strep infection suddenly get well after several doses of antibiotics is a witness to one of the great developments of 20th-century medicine. Researchers are experimenting with novel uses all the time. Italian scientists reported that tetracycline may weaken the prions that cause mad cow disease. Many investigators are looking for the antibiotic combination that will tame the inflammatory aspects of heart disease.

The headline on Dr. Finland’s 1978 editorial was “And the Walls Come Tumbling Down.” The walls are cracked but still there. Wise use of antibiotics will keep them standing.

(This article was first printed in the November 2002 issue of the Harvard Health Letter. For more information or to order, please go to http://www.health.harvard.edu/health.)

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