Characterization of resistance phenotype and cephalosporin activity in oxacillin-resistant Staphylococcus aureus.

Forty isolates of methicillin-resistant Staphylococcus aureus were tested versus oxacillin at 30 and 35 degrees C with and without 2% NaCl supplementation of Mueller-Hinton broth and classified as having resistance that was low (MIC, less than or equal to 16 micrograms/ml) or high (MIC, greater than or equal to 32 micrograms/ml) and temperature or NaCl dependent. Only three isolates had low-grade resistance at both 30 and 35 degrees C; for two isolates the MICs at 35 degrees C were greater than or equal to 4 X the MICs at 30 degrees C. NaCl usually increased the MICs two- to fourfold. Efficiency of plating studies were performed on strains selected for their level of oxacillin resistance and according to temperature-related difference in MICs. Most strains appeared to represent the heterogeneous resistance phenotype. Cefamandole MICs were little affected by temperature but increased with NaCl. With three exceptions, cefamandole MCBs were less than or equal to 4 X MICs. For only six isolates were cefuroxime MICs less than or equal to 16 micrograms/ml. Four strains that were susceptible to both cefuroxime and cefamandole were selected for time-killing curve studies at inocula of 10(7) CFU/ml. At 8 X MIC, cefuroxime failed to reduce the concentration of any strain by greater than or equal to 3 X log10 CFU/ml. Killing of greater than or equal to 3 X log10 CFU/ml was achieved by cefamandole at 4X and 8 X MIC in one strain, at 8 X MIC only in two strains, and by neither 4 X nor 8 X MIC in one strain. Within therapeutically attainable blood levels, cefuroxime is essentially inactive and cefamandole is variably bactericidal against oxacillin-resistant s. aureus.