POSSIBLE PREVENTION OF IN-VITRO SELECTION OF RESISTANT STREPTOCOCCUS-PNEUMONIAE BY BETA-LACTAMASE INHIBITORS

The development of resistance in vitro in five strains of Streptococcu s pneumoniae (3 with full susceptibility and 2 with intermediate susce ptibility to penicillin) was investigated by serial passages in the pr esence of subinhibitory concentrations of amoxicillin and ampicillin. At the end of passaging, MICs of antibiotics for all the strains incre ased by a factor of four or more, reaching at least intermediate level s. MICs of cephalosporins, ampicillin and amoxicillin increased for al most all variants obtained. Similar results were obtained with amoxici llin plus clavulanic acid at a ratio of 2:1 and at a constant concentr ation of 2 mu g/ml, and with ampicillin plus sulbactam at a ratio 2:1. In contrast, no significant modification of MIC was seen with ampicil lin plus sulbactam at a constant concentration of 4 mu g/ml sulbactam. These results suggest interaction of sulbactam with penicillin bindin g proteins as described previously for other bacterial species, and me rit further investigation.