In vitro activity against clinically important gram-positive and gram-negative bacteria of sulbactam, alone and in combination with ampicillin, cefotaxime, mezlocillin, and piperacillin

The in vitro effects of the single agents, and the synergistic/antagonistic action of three different combinations of ampicillin (AMP, CAS 69-53-4), cefotaxime (CTX, CAS 63527-52-6), mezlocillin (MEZ, CAS 51481-65-3), and piperacillin (PIP, CAS 61477-96-1) with the beta-lactamase inhibitor sulbactam (SUL, CAS 68373-14-8) were determined against 675 gram-positive and gram-negative, both aerobic and anaerobic bacteria. All the combinations of sulbactam and the antibiotics (1: 1, 1:2 and 1:4) exhibited very similar synergistic action. The percentage of the total strains tested for which synergistic activity was found was 51% with SUL + AMP (1:1), 24% with SUL + CTX (1:1), 31% with SUL + MEZ (1:1), and 28% with SUL + PIP (1:1). A fourfold or greater reduction of MIC's in the comparison with the antibiotics alone was found with 23% of the total strains tested for the SUL + AMP, with 9% of the strains tested with SUL + CTX, with 11% of the strains tested with SUL + MEZ, and with 15% of the strains tested with the SUL + PIP-combination. In the presence of sulbactam, 18% of the strains tested showed a significant reduction in the number of resistant strains with ampicillin, 7% with cefotaxime, 16% with mezlocillin, 14% with piperacillin, and in parallel there was an increase in the number of fully susceptible strains (shift from resistant or moderately sensitive to sensitive) by about 14%. In comparison with the antibiotic alone, the most marked reductions in the number of resistant strains on combination with sulbactam were as follows (the percentage of reduction is shown in brackets): for SUL + AMP and Acine-tobacter spp. (39% fewer resistant strains). Citrobacter spp. (-60%), Enterobacter aerogenes (-48%), Klebsiella oxytoca (-49%), Klebsiella pneumoniae (-63%), Morganella morganii (-74%), and Proteus vulgaris (-55%); for SUL + CTX and Acinetobacter spp. (-38%), Enterobacter cloacae (-6%), Klebsiella pneumoniae (-16%), Serratia marcescens (-9%), and Bacteroides fragilis (-31%); for SUL + MEZ and Acinetobacter spp. (-68%), Citrobacter spp. (-27%), Enterobacter spp. (-23%), Klebsiella pneumoniae (-32%), and Serratia marcescens (-19%); for SUL + PIP and Acinetobacter spp. (-41%), Citrobacter spp. (-30%), Klebsiella spp. (-30%), and Serratia marcescens (-33%).