IMPACT OF SULBACTAM ON THE INVITRO ACTIVITY OF MEZLOCILLIN, PIPERACILLIN, AND CEFOTAXIME

The in vitro activity of mezlocillin (MZL, CAS 51481-65-3), piperacillin (PIP, CAS 61477-96-1) and cefotaxim (CTX, CAS 63527-52-6) alone and in combination with sulbactam (SBT; CAS 68373-14-8) against mezlocillin-resistant pathogens was determined in a multicenter study. A total of 870 strains were investigated (481 Enterobacteriaceae, 57 Pseudomonas aeruginos, 41 Acinetobaster spp., 194 Bacteroides fragilis, and 97 Staphylococcus spp.). Determinations of MIC were performed according to DIN-guidelines (agar-dilution method for aerobes and microbroth-dilution method for anaerobes). Sulbactam was added in fixed concentrations of 5 mg/l and 10 mg/l. In all sulbactam-combinations examined mean MIC as well as MIC50 and MIC90 were reduced compared to the respective values for the antibiotics alone. Consequently, percentages of susceptible strains increased significantly: i.e. for Enterobacteriaceae: MZL 1% vs. MZL + 10 mg/l SBT 53%; PIP 4% vs. PIP + 10 mg/l SBT 54%; CTX 52% vs. CTX + 10 mg/l SBT 68%. The effect of sulbactam was most pronounced in Bacteroides spp. with an increase in susceptible strains from 2% to 97% for MZL, from 6% to 95% for PIP and from 7% to 98% for CTX. The results indicate that by adding sulbactam the in vitro activity of mezlocillin, piperacillin and cefotaxim against resistant pathogens is augmented significantly. In addition, the spectrum of antibacterial activity is extended to anaerobic pathogens such as Bacteroides spp. The availability of sulbactam as a monosubstance for combination with various beta-lactam-antibiotics thus represents a useful improvement of therapeutic options in bacterial infections.