The Antibiotics Crisis

We're in the midst of an escalating arms race with the microbe, and we may be losing

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From the filthy, louse-ridden cells of Russia's overcrowded prisons has emerged a serial killer that is as devious as it is dangerous. Its name is Mycobacterium tuberculosis, and it sallies forth on spumes of sputum each time an infected inmate coughs or sneezes. As many as 10% of Russia's million prisoners suffer active TB; in at least 1 case out of 5, the bacillus is a multidrug-resistant strain. Now M. tuberculosis in virulent forms is stalking ordinary citizens in Russian cities and towns, and soon, if it hasn't done so already, it will hitch a ride on an airplane, a bus, a train and escape into the rest of the world.

Mycobacterium tuberculosis. Plasmodium falciparum. Staphylococcus aureus. Streptococcus pneumoniae. Enterococcus faecium. Neisseria gonorrhoeae. The list of microbial scourges that have developed immunity to one or more of the drugs used to treat them is growing ever longer, and in a number of cases physicians are running out of options. In U.S. hospitals, more than 20% of all enterococcus infections, which include infections of the gastrointestinal tract, heart valve and blood, are now resistant to vancomycin, for many years the antibiotic of last resort. Even more worrisome, insensitivity to vancomycin--which nurses and physicians in intensive-care units refer to as the big gun--is showing up in the dangerous family of staphylococcus bacteria.

That's the bad news. The good news is that help appears to be on the way, and with a little luck it might just arrive in time. For after years of paying scant attention to infectious diseases, pharmaceutical companies have begun to comb through the vast chemical libraries assembled over the past decade in search of new antimicrobial agents. The effort is starting to pay off. Since September 1999, the U.S. Food and Drug Administration has approved two new antibiotics that target both the enterococci and staphylococci. One--linezolid--seems particularly promising; it represents the first new class of antibiotics to come on the market in 35 years.

Many more such breakthroughs are needed, however, especially for diseases, such as tuberculosis and malaria, that are raging out of control in much of the world. It is sobering to note that more than 400 million people fall ill with malaria each year; of these, up to 3 million die, most of them children. With resistance to once effective antimalarials like chloroquine now widespread in Asia, Africa and South America, the prognosis could not seem more grim. "We're in a desperate situation," says Robert G. Ridley of the Swiss-based Medicines for Malaria Venture.

What makes the situation so desperate, experts agree, is that new and more effective drugs are not, in themselves, enough. As Richard Colonno, vice president of drug discovery for infectious disease at Bristol-Myers Squibb, sees it, what new drugs do is reset a pathogen's biological clock. They buy time, but eventually resistance to these compounds will also arise.

Why? In a word, evolution.

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