First report of methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in Thailand

To investigate whether there are methicillin-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin in Thailand, a total of 155 MRSA strains isolated from patients hospitalized between 1988 and 1999 in university hospitals in Thailand were tested for glycopeptide susceptibility. All the strains were classified as susceptible to vancomycin and teicoplanin when judged by NCCLS criteria for glycopeptide susceptibility using the agar dilution MIC determination. Vancomycin MICs at which 50 and 90% of the isolates tested were inhibited (MIC50 and MIC(90), respectively) were 0.5 and 1 microg/ml, respectively, with a range of 0.25 to 2 microg/ml. For teicoplanin, MIC50 and MIC90 were 2 microg/ml, with a range of 0.5 to 4 microg/ml. However, one-point population analysis identified three MRSA strains, MR135, MR187, and MR209, which contained subpopulations of cells that could grow in 4 microg of vancomycin per ml. The proportions of the subpopulations were 2 x 10(-4), 1.5 x 10(-6), and 4 x 10(-7), respectively. The subsequent performance of a complete population analysis and testing for the emergence of mutants with reduced susceptibility to vancomycin (MIC > or = 8 microg/ml) confirmed that these strains were heterogeneously resistant to vancomycin. Two of these strains caused infection that was refractory to vancomycin therapy. Pulsed-field gel electrophoresis showed that the two strains had identical SmaI macrorestriction patterns and that they were one of the common types of MRSA isolated in the hospital. This is the first report of heterogeneous resistance to vancomycin in Thailand and an early warning for the possible emergence of vancomycin resistance in S. aureus in Southeast Asia.