The influence of sulbactam on the in vitro activity of mezlocillin, piperacillin and cefotaxime

Abstract In a multicentre study, the in-vitro activity of mezlocillin (MEZ, Chemical Abstract Service [CAS] 51481-65-3), piperacillin (PIP, CAS 61477-96-1) and cefotaxime (CTX, CAS 63527-52-6) against mezlocillin-resistant organisms was determined alone and in combination with the β-lactamase inhibitor sulbactam (SBT, CAS 68373-14-8). A total of 870 strains were investigated (481 Enterobacteriaceae, 57 Pseudomonas aeruginosa , 41 Acinetobacter spp., 194 Bacteroides fragilis and 97 Staphylococcus spp.). MIC values were determined using the agar dilution test (aerobic organisms) or the microbroth dilution test ( Bacteroides spp.) in accordance with Deutsche Industrie fur Normung 58 940. SBT was added in fixed concentrations of 5 mg/l and 10 mg/l. For all combinations with SBT investigated, the geometric mean of the MIC and the MIC 50 and MIC 90 values were reduced as compared with the antibiotic alone (without SBT). Consequently, the proportion of sensitive strains was appreciably increased, for example in the Enterobacteriaceae: MEZ 1%, MEZ + 10 mg/l SBT 53%; PIP 4%, PIP + 10 mg/l SBT 54%; CTX 52%, CTX + 10 mg/l SBT 68%. The effect of SBT was especially pronounced on Bacteroides spp. For this organism, the proportion of sensitive strain rose from 2% to 97% (MEZ), 6% to 95% (PIP) and from 7% to 98% (CTX). The results show that adding SBT appreciably enhances the activity of MEZ, PIP and CTX against resistant strains of microorganism, and extends the activity spectrum to include anaerobic organisms. Thus the availability of SBT as a single-agent preparation for use in combination with various β-lacta antibiotics represents a worthwhile enlargement of the therapeutic armamentarium for treating bacterial infections.