Troubling Trends Converge: Drug-resistant Bacteria Gaining Genes For Virulence

Although all three children were previously healthy, the infectioncaused severe sepsis, rapid clinical deterioration and bleeding intothe adrenal glands, a complication, known as Waterhouse-Friderichsensyndrome, that is usually associated with fulminant bacterialmeningitis.

Two of the three bacterial strains were resistant to standardantibiotics. In all three cases, the disease progressed so rapidly thatneither standard nor alternative antibiotics had an effect.

"What we saw in these patients is not in the textbooks," saidRobert Daum, M.D., professor of pediatrics at the University of Chicagoand senior author of the study. "This is the first time this unusualsyndrome 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 becomequite common. At the same time, reports of virulent newer strains ofStaph that can cause invasive disease, extensive tissue damage anddeath have increased.

"These bacteria have picked up genes that enable them to evademost of the drugs we used to employ to treat them," Daum said, "and nowthey are combining that with genes for various toxins that can causesevere illness."

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

Many physicians initially had doubts, but since then cases ofcommunity-acquired methicillin-resistant Staphyllococcus aureusinfections (now known as CA-MRSA) have been detected in most major U.S.cities and several rural settings , and subsequently in Europe, Asiaand 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 ofpeople. Staph is one of the most common causes of skin infections, suchas pimples or boils, which can usually be treated without antibiotics.It can also cause serious wound infections, bloodstream infections orpneumonia.

Recently, however, physicians around the country have beendescribing increasingly virulent Staph infections that caused by thecommunity-associated strains of MRSA. Last April, for example, authorsfrom California described cases of necrotizing fasciitis (like"flesh-eating disease") and necrotizing pneumonia (an aggressivetissue-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 forseveral years. The difficult-to-treat, drug-resistant strains arebecoming more and more common outside of the hospital setting. Thesecommunity-acquired resistant strains appear to spread more easily thanthe better-known hospital-based microbes. Rare but devastatingtoxicities, such as the ones described in this paper, are beingrecognized. And as yet, scientists know relatively little about thecommunity-acquired variations of MRSA.

"This is something that demands our attention," Daum said. "Weneed to learn a lot more about this microbe and the genes it hascollected that have enabled it to move so quickly. We need to findbetter ways to treat this. And we need to work toward finding a vaccinethat can prevent Staph infections. That is the only way we have evertruly beaten an infectious disease."

The National Institute ofAllergy and Infectious Diseases, the Centers for Disease Control andPrevention, and the Grant HealthCare Foundation supported thisresearch. 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 ofChicago and Valerie Arangelovich, M.D., Michel Humilier, M.D.,of theCook County Medical Examiner's Office.