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Bad bugs, few drugs

Henry I. Miller
October 23, 2007

There is a constant war between pathogenic bacteria and humans, and the microbes seem to be winning. New data from the Centers for Disease Control (CDC) indicate the incidence of serious invasive infections from a strain of bacteria resistant to most first-line, commonly used antibiotics was higher than previously thought. The CDC estimates methicillin-resistant Staphylococcus aureus (MRSA) kills 18,000 Americans each year and causes serious infections in more than 90,000.

The phenomenon is not new, but reports of outbreaks in schools across the nation and the death of a high school student in Virginia earlier this month have focused national attention on the problem.

The medical community has been worried for years about growing antibiotic resistance in many kinds of bacteria. Especially if an infection is contracted in a hospital — in a surgical wound, for example, or in the form of pneumonia — there is a high probability the bacteria responsible will be resistant to one or more antibiotics, and the outcome is often deadly. Almost 2 million patients contract infections in U.S. hospitals each year — approximately 4½ percent of admissions — and 100,000 die, according to earlier data from the CDC.

The death rate in such cases is alarmingly high not because the patients initially are gravely ill, but because hospital germs increasingly are resistant to multiple antibiotics: About 70 percent of those infections are resistant to at least one drug, so the infections are hard to treat. In many cases, we"re already out of good second- or third-line alternatives that are effective, can be administered by mouth and have few side effects, so we must resort to drugs that are inconvenient to administer or have significant toxicity.

Many bad bugs are spreading beyond our hospitals into the greater community. Bacteria are masters of evolutionary adaptation: Given sufficient time and exposure, they use a variety of clever genetic and metabolic tricks to resist any drug we invent. There is no antibiotic in clinical use today to which some resistance has not developed. A future with few effective antibiotics would be treacherous; many of today's routine medical procedures, from surgical operations to chemotherapy, would be far more dangerous if we permit the bacteria to outwit us.

To combat this public health emergency, important initiatives are under way by both government and the private sector to promote more sparing and intelligent use of antibiotics. Regulators and livestock producers are collaborating to reduce the amounts of antibiotics used to prevent disease in livestock, and many HMOs have adopted policies that restrict antibiotics to infections that seem unequivocally to be caused by bacteria. (For example, patients should not routinely get antibiotics for colds, which are caused by viruses, not bacteria.)

The CDC is promoting four strategies to prevent antibiotic resistance in health-care centers — prevent infection, diagnose and treat infection, use antimicrobials wisely, and prevent transmission — but federal officials have paid little attention to the flip side of the problem: the shortage of new antibiotics.

Twenty years ago, about a half-dozen new antibiotics would appear on the market each year; now it's at most one or two. For decades we've relied largely on new variations on old tricks to combat rapidly evolving pathogens: Most antibiotics in use today are chemically related to earlier ones discovered between 1941 and 1968. During the last 38 years, only two antibiotics with truly novel modes of action have been introduced — Zyvox in 2000 and Cubicin in 2003, the latter of which must be infused intravenously.

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