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Drug Blitz Blunts Bugs Resistance

Short, high dose regimen prevents antibiotic resistance

TUESDAY, July 3, 2001 (HealthDayNews) -- When it comes to cutting the risk of drug-resistant upper respiratory infections, short and intense beats long and moderate, a new study says.

Children who got a short course of high-dose antibiotics were less likely to develop drug-resistant ear, sinus and airway infections than those who got the usual, prolonged round of therapy, researchers say.

The study, led by researchers at the Centers for Disease Control and Prevention (CDC), is reported this week in the Journal of the American Medical Association.

Pneumococcal infections, such as pneumonia and meningitis, kill roughly 1 million children under age 5 each year worldwide. Although vaccines can prevent the bacterial infections, it's not used nearly enough, experts say. And the diseases are still a serious problem both in the United States and abroad, particularly for the very young and the elderly.

A major problem has been the rise of drug-resistant forms of pneumococcal germs, such as Streptococcus pneumoniae. The National Foundation for Infectious Diseases says drug-resistant pneumococcus causes thousands of cases of meningitis and blood infections each year, in addition to 150,000 cases of pneumonia and more than 1 million ear infections.

Between 1987 and 1992, invasive pneumococcal infections resistant to penicillin rose more than 60-fold, from 0.02 percent to 1.3 percent, says the CDC. In some areas of the United States, more than 30 percent of the infections aren't affected by the usual antibiotic drugs, the agency says.

Recent studies have shown that shorter but more intensive courses of antibiotics work just as well as longer treatment regimens for some bacterial diseases and may better prevent germs from evolving defenses to the drugs.

The latest study, led by CDC epidemiologist Stephanie Schrag, was done in Santo Domingo, in the Dominican Republic, between October 1999 and July 2000. It followed 795 children taking antibiotics for airway infections, including those of the sinus and middle ear.

Tests showed that about 74 percent of the children, ages 6 months to 5 years, had drug-sensitive bacteria, and 26 percent were infected with strains of S. pneumoniae that aren't killed by penicillin.

Half the children received two daily doses of amoxicillin, a form of penicillin, based on their body weight, for five days, while the rest were given the same amount of amoxicillin spread over 10 days.

Children on the short course were about 25 percent less likely than those on the long course to develop drug-resistant infections two to three weeks after treatment ended, the researchers say. They also were about 25 percent less prone to develop resistance to two other antibiotics, trimethoprim and sulfamethoxazole.

The short-course therapy helped most in families in which the sick child had at least two siblings; the risk of resistance in those children was 28 percent lower. Schrag says. The short-course, high-dose "blitzkrieg approach" probably prevents infected children from passing their illness to their family members during treatment, and from reacquiring it in a stronger, more-resistant form later, says Schrag.

Not surprisingly, the children were better able to stick with the short course of treatment. Researchers say 82 percent of those on the short course completed their regimen, compared with 74 percent of the children on the longer regimen.

Although the study was done in the Caribbean, Schrag says similar results are likely in the United States where drug resistance is more common. A working group for the CDC already has recommended that doctors prescribe a short-course regimen for S. pneumoniae infections in regions where drug-resistance is high, such as Tennessee and Minnesota, Schrag says. The World Health Organization also has recommended a five-day therapy.

Dr. Meg Fisher, chair of pediatrics at Monmouth Medical College in Long Branch, N.J., and an advisor on infectious diseases to the American Academy of Pediatrics, says the CDC study leaves several questions unanswered.

The effect of the short-course therapy was significant, but not overwhelmingly so, Fisher says. "The impact was pretty small. In fact, it's not really very impressive," she says. What's more, the researchers didn't test whether a short course of a conventional dose of amoxicillin would have been equally effective as the higher doses used in the study.

Most important, Fisher says nearly half the children in the study received drugs when they probably didn't need them -- a constant problem in an over-prescribing culture like the United States. and a serious problem that fuels resistance. Previous studies have shown that many ear infections get better just as quickly when they're left alone as when they're treated with antibiotics, for instance.

"Anything that we could do to slow down the emergence of resistance is important," Fisher says. But she says the best strategy may be to reduce unnecessary prescriptions rather than cut their courses in half. In this country, half of adults and half of children who go to a doctor with a common cold are sent home with a prescription for an antibiotic, despite the fact that colds are viral infections that don't respond to bacteria-killing drugs.

Dr. Thomas Lynch III, a lung specialist at the University of Michigan, says bacterial resistance research mainly done in a lab dish doesn't translate well in terms of clinical complications.

"There are relative degrees of resistance. Intermediate levels of resistance in the test tube does not have adverse clinical outcomes in most circumstances," says Lynch. He says the most notable exception is meningitis, a potentially deadly brain infection. "It turns out that probably only 1 to 2 percent or less have very high resistance, and these are the ones that are most important" clinically.

What To Do

To learn more about drug-resistant strep infections, check the CDC or Vanderbilt University.

You can also learn more about the rise of drug-resistant germs from the U.S. Food and Drug Administration.

SOURCES: Interviews with Stephanie Schrag, D.Phil., epidemiologist, CDC, Atlanta; Thomas Lynch III, M.D., professor of internal medicine, University of Michigan Medical School, Ann Arbor, and Meg Fisher, M.D., chair, department of pediatrics, Monmouth Medical Center, Long Branch, N.J.; July 4, 2001, Journal of the American Medical Association
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