[Clinical laboratory approach for estimating effective administrative dose of sulbactam/cefoperazone]

Sulbactam/cefoperazone (SBT/CPZ) is a preparation containing CPZ and SBT, an inhibitor of beta-lactamases, at the ratio 1:1. The reliability of the SBT/CPZ disc susceptibility test in estimating approximate values of MICs and the utilization of the test in the evaluation of proper administrative doses were studied using 365 strains of clinical isolates. The antimicrobial activity of SBT/CPZ was stronger than that of CPZ alone. This increase in the antimicrobial activity due to the addition of SBT was well observed in the disc diffusion susceptibility test and MIC values. The MIC80 of SBT/CPZ against Staphylococcus aureus was 12.5 micrograms/ml, while that of CPZ alone was 50 micrograms/ml. MIC80s of SBT/CPZ against Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Enterobacter aerogenes were smaller than those of CPZ, and were 0.20, 12.5, 25 and 3.13 micrograms/ml, respectively. However, MIC80s of SBT/CPZ against Staphylococcus epidermidis, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris were not changed compared to those of CPZ alone, and MIC80s were 6.25, 0.20, 0.78, and 0.78 micrograms/ml, respectively. The reliability of the SBT/CPZ disc diffusion susceptibility test in the quantitative estimation of antimicrobial activities was well demonstrated using commercialized 8 mm diameter discs (Showa) and 6 mm diameter discs prepared in this laboratory, both of which contained 30 micrograms of CPZ and 30 micrograms of SBT. These disc susceptibility test results were well correlated with MICs, hence the SBT/CPZ disc susceptibility test should be useful for the estimation of approximate MIC values. To interpret results of the Showa SBT/CPZ disc test, the following 4 category classification was used: (¿) MIC less than or equal to 3 micrograms/ml, (¿ 3 micrograms/ml less than MIC less than or equal to 15 micrograms/ml, (¿15 micrograms/ml less than MIC less than or equal to 60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. In both 6 and 8 mm diameter disc tests, when uniform break points of inhibitory zone diameter were similarly applied to all strains isolated clinically, some strains of S. aureus, E. faecalis, and P. aeruginosa, brought false positive (susceptible) results showing slightly greater inhibitory zone diameters compared to MICs. However, if different break points against P. aeruginosa as indicated in this study were applied and E. faecalis was excluded from the test, excellent results were obtained in the quantitative estimation of MICs. Antimicrobial activities of antibiotic agents have been reported to be reduced by serum protein binding.(ABSTRACT TRUNCATED AT 250 WORDS)