Researchers Report Emergence of Antibiotic Resistance during Vancomycin Therapy

Antibiotic Combination Shown To Be Effective against Resistant Bug

A team of researchers led by The Rockefeller University’s Alexander Tomasz, Ph.D., have described the case of a 79-year-old patient whose death in a New York metropolitan area hospital last March was associated with a bloodstream infection caused by a multidrug-resistant strain of Staphylococcus aureus. The report, published in the Feb. 18 issue of the New England Journal of Medicine (NEJM), showed that the bacteria, which had decreased susceptibility to vancomycin, could be treated effectively with a combination of antibiotics.

“We think that this is the first demonstration that selection for strains with increased resistance to vancomycin can occur during therapy,” says Tomasz, senior author of the paper and professor and head of the Laboratory of Microbiology.

The case described in the NEJM article was the fourth in the world associated with infections caused by multiresistant strains of Staphylococcus aureus (MRSA) that also show partial resistance to vancomycin, a drug often described as the “last resort” antibiotic against these dangerous pathogens that cause many hospital-acquired infections in the United States and elsewhere.

“The emergence of vancomycin-resistant Staphylococcus aureus strains emphasizes the importance of appropriate vancomycin dosing to assure complete eradication of the bacteria,” says Richard B. Roberts, M.D., a co-author of the report and an adjunct professor at Rockefeller and professor of medicine at New York Hospital-Cornell Medical Center.

A hopeful finding reported by the Rockefeller team is that a combination of two commonly used antibiotics, oxacillin and vancomycin, produced a synergistic effect and killed the vancomycin-resistant MRSA very efficiently in the test tube.

“If these results can be translated into the clinical setting, they suggest that a combination of vancomycin and oxacillin may be an effective therapeutic regimen against vancomycin-resistant staphylococci,” says Tomasz.

Antibiotic resistance is a growing public health problem. In a study published in the July 1998 issue of theJournal of Infectious Diseases, the Rockefeller group in collaboration with colleagues at the Public Health Research Institute used molecular fingerprinting techniques to demonstrate the extensive spread of a single multidrug-resistant Staphylococcus aureus strain dubbed “the New York clone of MRSA” in 12 hospitals in the New York metropolitan area.

Tomasz and Roberts’s co-authors are first author Krzysztof Sieradzki, Ph.D., a postdoctoral fellow at Rockefeller, and Stuart W. Haber, M.D., of United Hospital Medical Center in Port Chester, N.Y.

The research described in the NEJM paper was supported in part by The Glickenhaus Foundation, The Bodman and Achelis Foundations, and the Cary L. Guy Foundation.