Reversion of the glycopeptide resistance phenotype in Staphylococcus aureus clinical isolates

The recent identification of glycopeptide intermediate-resistant Staphylococcus aureus (GISA) clinical iso-lates has provided an opportunity to assess the stability of the glycopeptide resistance phenotype by nonse-lective serial passage and to evaluate reversion-associated cell surface changes. Three GISA isolates from the United States (MIC of vancomycin 5 8 mg/ml) and two from Japan (MICs of vancomycin 5 8 and 2 mg/ml) were passaged daily on nutrient agar with or without vancomycin supplementation. After 15 days of passage on nonselective medium, vancomycin- and teicoplanin-susceptible revertants were obtained from each GISA isolate as determined by broth dilution MIC. Revertant isolates were compared with parent isolates for changes in vancomycin heteroresistance, capsule production, hemolysis phenotype, coagulase activity, and lysostaphin susceptibility. Several revertants lost the subpopulations with intermediate vancomycin resistance, whereas two revertants maintained them. Furthermore, although all of the parent GISA isolates produced capsule type 5 (CP5), all but one revertant tested no longer produced CP5. In contrast, passage on mediu