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Danger: Vancomycin-Resistant Staphylococcus aureus

The glycopeptide vancomycin has assumed a pivotal role as our last safeguard antibiotic against MRSA, Staphylococcus aureus strains already resistant to all cephalosporins and semisynthetic penicillins. This vancomycin safety net is now starting to unravel, as outlined in two reports describing three patients from Michigan, New Jersey, and New York who developed infections with glycopeptide-intermediate-sensitive S. aureus (GISA).

All infections involved chronically ill individuals with chronic renal failure and indwelling medical devices, who received prolonged vancomycin therapy for MRSA infections. The Michigan and New Jersey patients each received 18 weeks of intravenous vancomycin therapy in 1997 for MRSA before GISA appeared. GISA was eradicated from both patients by removing indwelling medical devices and using varying combinations of antimicrobials, including rifampin, trimethoprim-sulfamethoxazole, vancomycin, and gentamicin. Both patients eventually died of underlying illnesses. The New York patient received 6 weeks of intravenous vancomycin treatment for MRSA before GISA bacteremia and death occurred 4 weeks later.

Extensive contact-tracing studies of the Michigan and New Jersey patients revealed no GISA strains among 177 medical or household contacts. GISA isolates from all three patients were inhibited by vancomycin MICs of 8 to 16 µg/ml, in an analysis requiring quantitative broth micro-dilution methods instead of disk diffusion testing. Each GISA isolate compared by electron microscopy with control MRSA strains exhibited thickened cell wall material on its outer surface. The New York strain bound increased amounts of vancomycin to this material, potentially explaining the mechanism of vancomycin resistance. Fortunately, this strain's resistance did not stem from vanA or vanB resistance genes transferred from vancomycin-resistant enterococci. Unfortunately, the strain shared close genetic identity with a MRSA clone, widespread in metropolitan New York, that developed properties of a GISA strain in vitro. Combinations of beta-lactam antibiotics and vancomycin appear to kill GISA synergistically in vitro, suggesting a potential therapeutic regimen for this pathogen.

Comment: The appearance of these three U.S. strains of GISA, plus a fourth strain described in Japan in 1996, is an ominous development. Vancomycin must only be used when it is definitely required; practice guidelines and antibiotic stop orders can help ensure appropriate use. Treatment failures of prolonged vancomycin use against S. aureus should prompt a search for GISA, using quantitative broth microdilution methods instead of disk diffusion testing. If GISA is present, appropriate infection-control measures must be instituted.

— N Blacklow

Published in Journal Watch Infectious Diseases April 1, 1999

Citation(s):

Smith T et al. Emergence of vancomycin resistance in Staphylococcus aureus. N Engl J Med 1999 Feb 18 340 493-501.

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Sieradzki K et al. The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection. N Engl J Med 1999 Feb 18 340 517-523.

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Waldvogel FA. New resistance in Staphylococcus aureus. N Engl J Med 1999 Feb 18 340 556-557.

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