Troubling trends converge

September 22, 2005

In a "Brief Report" in the 22 September 2005 issue of the New England Journal of Medicine, researchers at the University of Chicago describe three cases of rapidly progressive and ultimately fatal Staphylococcus aureus infections in small children.

Although all three children were previously healthy, the infection caused severe sepsis, rapid clinical deterioration and bleeding into the adrenal glands, a complication, known as Waterhouse-Friderichsen syndrome, that is usually associated with fulminant bacterial meningitis.

Two of the three bacterial strains were resistant to standard antibiotics. In all three cases, the disease progressed so rapidly that neither standard nor alternative antibiotics had an effect.

"What we saw in these patients is not in the textbooks," said Robert Daum, M.D., professor of pediatrics at the University of Chicago and senior author of the study. "This is the first time this unusual syndrome has been described in patients with a Staph infection."

Such cases, although rare, highlight a disturbing convergence. In the last decade, drug-resistant strains of Staph. aureus have become quite common. At the same time, reports of virulent newer strains of Staph that can cause invasive disease, extensive tissue damage and death have increased.

"These bacteria have picked up genes that enable them to evade most of the drugs we used to employ to treat them," Daum said, "and now they are combining that with genes for various toxins that can cause severe illness."

Until the late 1990s, drug-resistant Staph infections were viewed as a purely hospital-acquired illness. In the 25 February 1998 issue of JAMA, however, a team led by Daum published the first study showing that Staphylococcus aureus infections that were already resistant to many types of antibiotics were being seen in children outside of the hospital environment.

Many physicians initially had doubts, but since then cases of community-acquired methicillin-resistant Staphyllococcus aureus infections (now known as CA-MRSA) have been detected in most major U.S. cities and several rural settings , and subsequently in Europe, Asia and South America.

This bacterium, often referred to simply as "Staph," is common, found on the skin and in the noses of an estimated 30 percent of people. Staph is one of the most common causes of skin infections, such as pimples or boils, which can usually be treated without antibiotics. It can also cause serious wound infections, bloodstream infections or pneumonia.

Recently, however, physicians around the country have been describing increasingly virulent Staph infections that caused by the community-associated strains of MRSA. Last April, for example, authors from California described cases of necrotizing fasciitis (like "flesh-eating disease") and necrotizing pneumonia (an aggressive tissue-destroying lung infection) caused by community-acquired MRSA.

These lethal manifestations are the "tip of the iceberg," Daum said, "but this is getting to be a substantial iceberg."

The overall rate of Staph infections has been increasing for several years. The difficult-to-treat, drug-resistant strains are becoming more and more common outside of the hospital setting. These community-acquired resistant strains appear to spread more easily than the better-known hospital-based microbes. Rare but devastating toxicities, such as the ones described in this paper, are being recognized. And as yet, scientists know relatively little about the community-acquired variations of MRSA.

"This is something that demands our attention," Daum said. "We need to learn a lot more about this microbe and the genes it has collected that have enabled it to move so quickly. We need to find better ways to treat this. And we need to work toward finding a vaccine that can prevent Staph infections. That is the only way we have ever truly beaten an infectious disease."
The National Institute of Allergy and Infectious Diseases, the Centers for Disease Control and Prevention, and the Grant HealthCare Foundation supported this research. Coauthors of the paper include Patricia V. Adem, M.D., Christopher P. Montgomery, M.D., Aliya N. Husain, M.D., Tracy K. Koogler, M.D., and Susan Boyle-Vavra, Ph.D, of the University of Chicago and Valerie Arangelovich, M.D., Michel Humilier, M.D.,of the Cook County Medical Examiner's Office.

University of Chicago Medical Center

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