Killer Staph Is Hitting The Streets

Drug-defying strains of the bacteria have moved way beyond hospitals

The normally robust Drew Gooden, a forward with the Orlando Magic basketball team, startled his fans when he missed three games in March because of infected hair follicles on his leg. This was no ordinary infection, however.

Gooden, who at first thought he was suffering from spider bites, was laid low by a virulent staph bacteria. He received antibiotics through an intravenous drip for 72 hours while doctors repeatedly drained his leg. "People were trying to make fun, like it was nothing," Gooden said to reporters. "That was serious."

To say the least. Recent news of the battle against this superbug indicate that Gooden got off lightly. Staphylococcus aureus, the bacterium's official name, resides on the skin or in the nasal passages of one in three people. It is usually benign but can flare up to cause painful infections. For the past 30 years, hospitals have been battling a mutant form called methicillin-resistant S. aureus (MRSA) that is resistant to penicillin-related antibiotics and is especially lethal. Now this drug-defying strain is showing up in the general population. It can be deadly if it enters the blood stream, heart, or lungs, killing anywhere from 25% to 43% of its victims.

For years, the best treatment for MRSA was the powerful antibiotic vancomycin. But even this weapon has failed against new strains of staph that have emerged. Some infectious-disease experts predict that by 2010, 40% of staph infections will be vancomycin-resistant. And for the moment, there are few alternatives. Cubist Pharmaceuticals Inc. (CBST ) in Lexington, Mass., won approval in September for a new type of antibiotic, Cubicin, that works as well as vancomycin against staph. But experts figure it's only a matter of time before the bug learns to evade Cubicin, too.

Two small biotech companies are trying to get around the resistance problem by harnessing the body's own immune system. Nabi Biopharmaceuticals, in Boca Raton, Fla., is testing a vaccine, and Inhibitex Inc. in Alpharetta, Ga., is developing an engineered protein called a monoclonal antibody.

Microbe experts are intrigued by these approaches but doubt that they will be 100% effective. Meanwhile, the menacing staph bacteria continue to spread and evolve. "It's too early to know if we are going to have an epidemic," says Dr. Robert C. Moellering Jr., physician-in-chief of Beth Israel Deaconess Medical Center in Boston, "but this is a very invasive and potent pathogen."

MOVING TARGET. Moellering's concern is well-founded. Hospitals have always been breeding grounds for infection, but with MRSA proliferating, hospital-spawned infections are soaring. The Centers for Disease Control & Prevention estimates that the incidence of drug-resistant staph infections in intensive-care units, where they are most dangerous, doubled from 1987 to 1997. In England, British Medical Journal reported in February that 800 people died from drug-resistant staph infections in 2002, vs. 51 in 1993. Cases have also spiked in Japan, where in March three patients died of staph infections at the same hospital.

But it's the migration of drug-resistant staph out of hospitals that has epidemiologists most on edge. Alarm bells went off among infectious-disease specialists in 1999 when four healthy children in Minnesota and North Dakota died from MRSA infections, even though none had been anywhere near a hospital. There is no national database to track community-based infections, but anecdotal reports have poured in about breakouts in military barracks, athletic clubs, and prisons.

It's not surprising that drug-resistant strains are common in hospitals. Widespread use of antibiotics gives the microbe more chances to develop resistance. But scientists aren't sure why these superbugs have spread to the community.

"Staph is uniquely adaptive," notes Dr. Franklin D. Lowy, professor of medicine at Columbia University. Because it is carried in the nose, the microbe has the opportunity to come in and out of hospitals with every visitor. Staph is also highly promiscuous, able to quickly exchange genes with other strains and even other species of bacteria. That makes the microbe a constantly moving target for antibiotics, which work by blocking production of certain enzymes that the bacteria need to survive. Confronted with a drug, rapidly evolving staph colonies grab genes from some other type of bacterium that codes for a different enzyme.

Nabi's vaccine avoids this problem by piggybacking on the immune system. Normally, staph microbes don't trigger an immune reaction thanks to a coating made of sugars, called polysaccharides, that enables them to avoid detection by the body. Nabi created its StaphVAX vaccine by linking sugar molecules obtained from purified staph to a nontoxic carrier protein. When the vaccine is injected, it prompts the immune system to make high levels of protective antibodies specific to the staph bacteria.

LIMITED APPLICATION. In a phase III clinical trial involving 1,804 patients with end-stage kidney failure -- a group with few defenses against bacteria -- StaphVAX cut staph infections over 40 weeks by 57%. The drug stopped working after 10 months but may last longer in patients who aren't as sick. Nabi is repeating the clinical trial with twice as many patients, and CEO Thomas H. McLain says the company hopes to seek approval by the end of 2005.

Inhibitex is also taking an immune-system approach. Its Aurexis monoclonal antibody binds to a protein found on the surface of virtually all strains of staph. Once attached, it alerts the immune system to the microbe's presence. A safety study was successfully completed in September, 2003, and Inhibitex is enrolling 60 patients for a Phase II trial.

Infectious-disease experts are cautious in their appraisal of both drugs. Neither would work well in a community setting -- it would be too difficult, and costly, to vaccinate a large population with StaphVAX, and Aurexis must be given intravenously. So for now, it seems, the superbugs have the upper hand.

By Catherine Arnst in New York

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