In-vitro evaluation of ampicillin/brobactam and comparison with other beta-lactam antibiotics

The ability of brobactam to inhibit beta-lactamases and the in vitro activity of ampicillin combined with brobactam was compared with another beta-lactamase inhibitor, clavulanic acid, and other beta-lactam antibiotics. Both inhibitors showed good and similar activity against staphylococcal penicillinase and most broad-spectrum beta-lactamases found in the Enterobacteriaceae, whether plasmid or chromosomally mediated. Both inhibitors were less active against chromosomally mediated cephalosporinases in Enterobacteriaceae, but brobactam was 8-50 times more potent than clavulanic acid. The amount and type of beta-lactamase produced by a particular bacterial strain was reflected in its sensitivity to a combination of ampicillin and brobactam, and correlated well with the sensitivity of extracted beta-lactamase to inhibition by brobactam. The in-vitro activity of ampicillin/brobactam in a 3:1 ratio was compared to amoxycillin/clavulanic acid (4:1 ratio), amoxycillin, cefaclor and cefuroxime. The two inhibitor combinations were generally of similar activity, but the brobactam combination had superior activity against Proteus vulgaris, Morganella morganii, Citrobacter freundii and Yersinia enterocolitica. The cephalosporins were less effective against the Bacteroides fragilis group, Prot. vulgaris and M. morganii, but had advantages in the case of Escherichia coli, Klebsiella spp. and C. diversus. The MBC of ampicillin/brobactam was similar to the MIC. No resistant sub-populations were observed amongst the staphylococcal strains investigated. Exposure of bacteria to sub-inhibitory levels of ampicillin/brobactam did not lead generally to the development of resistance.