Old Bugs Learn Some New Tricks

When antibiotics arrived 60 years ago, many experts thought it was the beginning of the end for infectious diseases. Sadly, they were wrong. Infections caused by viruses, fungi and other assorted critters never respond to antibiotics. As special drugs are developed for some of them, new foes such as bird flu crop up. And even bacteria, the true targets of antibiotics, have found ways to beat the rap. In most cases they change their genes to thwart antibiotics. Smart scientists fight back by creating new drugs--but, more often than not, the bugs find a way to give them the slip.

To see how it works--and what we can do about it--consider three important bugs that have recently found new ways to make us sick. The first is staph aureus, which has been part of the human condition since the beginning of recorded history. The bacterium's natural habitat is the human nose; at any one time, at least 25 percent of us harbor the germ. In most, it's a harmless fellow traveler, but it often travels from nose to hand to skin, where it causes pesky boils and infects "ingrown" hairs and nails. In an unlucky few, staph causes devastating infections of the blood and organs. These were highly lethal until penicillin came along. The drug was dramatically effective, but the bug rapidly changed its genes to produce penicillinase, an enzyme that chews up the antibiotic. Penicillin-resistant strains appeared first in hospitals, then spread to the community. By now, 95 percent of staph shrug off penicillin.

In response to the growing problem, researchers developed penicillinase-proof antibiotics. The first, in 1959, was methicillin, and a family of related drugs soon followed. But by 1960, methicillin-resistant staph aureus (MRSA) began to crop up in hospitals; by now it constitutes the majority of strains in some hospitals and has also exploded in the community.

Hospitals try to contain the spread of MRSA by handling infected patients with latex gloves and other precautions. At home, we should stress hand washing with soap and water as well as alcohol-based rubs. So far, community strains of MRSA are reassuringly susceptible to certain older oral antibiotics, but major infections should be treated with the same injected drugs used for hospital patients.

Compared with staph, Clostridium difficile ( C. diff ) is a newcomer. It was first diagnosed in 1978, when it appeared as an occasional cause of diarrhea in patients who were taking a particular antibiotic (clindamycin). By now, though, it is clear that virtually any antibiotic can trigger the problem. C. diff strikes at least 300,000 people in the United States each year, even some who haven't taken antibiotics. Many healthy people harbor a few C. diff among the millions of bacteria in the colon. When C. diff hangs out in the form of inert spores, it's harmless. But if antibiotic therapy knocks off the normal bacteria, C. diff springs to life, producing two toxins that attack the colon. Doctors can treat most cases by stopping the offending drug and prescribing metronidazole or vancomycin, oral antibiotics that target C. diff. But spore forms of the bug defy even these drugs, and diarrhea often recurs when treatment stops.

The next threat is a novel, highly virulent strain of C. diff that produces 16 to 23 times more toxin than its predecessors. Because the bug is so new, doctors have not yet determined if revised treatment guidelines are warranted. This new and dangerous form of C. diff makes it even more urgent that people with diarrhea, or people caring for people with diarrhea, scrupulously wash their hands with soap and water after any possible contact with the infected material to avoid spreading the germ or becoming infected themselves.

Finally, there's tuberculosis--a historic scourge of humankind. Even now, it is the leading infectious cause of death in the world, accounting for more than 2 million deaths a year. We've been much luckier in this country. As a result of improved social and economic conditions, the incidence of TB began to decline around 1900 and nearly disappeared with the discovery of anti-TB drugs in midcentury. But in 1984, an alarming upturn developed. It was fueled by HIV and homelessness, and it featured a rise in multidrug-resistant (MDR) TB. Ordinary TB can be cured by six months of combination therapy. But MDR strains defy the standard drugs.

In this country, TB plateaued in 1992 and has declined steadily since because of aggressive diagnosis and strict isolation of cases. Still, there's no room for complacency. In 2006, doctors in South Africa identified a new, extensive-ly drug-resistant (XDR) strain of TB. So far it has been confined to AIDS patients in South Africa, but it's a small world, and infections respect no borders. We need new drugs for TB. But we also need to use the resources that we already have to deliver medical care to the developing world. If we fight the war against TB on that turf, we may not have to fight it on our own turf.

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