Reversion of the glycopeptide resistance phenotype in Staphylococcus aureus clinical isolates

The recent identification of glycopeptide intermediate-resistant Staphyloco ccus aureus (GISA) clinical isolates has provided an opportunity to assess the stability of the glycopeptide resistance phenotype by nonselective seri al passage and to evaluate reversion-associated cell surface changes. Three GISA isolates from the United States (MIC of vancomycin = g mu g/ml) and t wo from Japan (MICs of vancomycin = 8 and 2 mu g/ml) were passaged daily on nutrient agar with or without vancomycin supplementation, After 15 days of passage on nonselective medium, vancomycin- and teicoplanin-susceptible re vertants were obtained from each GISA isolate as determined by broth diluti on MIG. Revertant isolates were compared,vith parent isolates for changes i n vancomycin heteroresistance, capsule production, hemolysis phenotype, coa gulase activity, and lysostaphin susceptibility. Several revertants lost th e subpopulations with intermediate vancomycin resistance, whereas two rever tants maintained them. Furthermore, although all of the parent GISA isolate s produced capsule type 5 (CP5), all but one revertant tested no longer pro duced CP5. In contrast, passage on medium containing vancomycin yielded iso lates that were still intermediately resistant to vancomycin, had no decrea se in the MIC of teicoplanin, and produced detectable CP5, No consistent ch anges in the revertants in hemolysis phenotype, lysostaphin susceptibility, or coagulase activities were discerned. These data indicate that the vanco mycin resistance phenotype is unstable in clinical GISA isolates. Reversion of the vancomycin resistance phenotype might explain the difficulty in iso lating vancomycin-resistant clinical isolates from the blood of patients wh o fail vancomycin therapy and, possibly, may account for some of the diffic ulties in identifying GISA isolates in the clinical laboratory.