Activity of mecillinam alone and in combination with other beta-lactam antibiotics

The in vitro activities of mecillinam, ticarcillin, cefamandole, and cefoxitin, singly and in all possible combinations, against 53 clinical isolates were studied by a checkerboard method of determining minimal inhibitory concentrations. For selected representative strains, bactericidal activity was determined by minimal bactericidal concentrations and killing curves. Mecillinam was the least active antibiotic against gram-positive cocci, Pseudomonas aeruginosa, and Bacteroides fragilis and the most active against Enterobacteriaceae. Reproducibility of mecillinam minimal inhibitory concentrations for susceptible Enterobacteriaceae was often poor, however, due to minor variations in inoculum size. When mecillinam resistance was observed with Enterobacteriaceae, partial inhibition could be demonstrated at concentrations below minimal inhibitory concentrations, and bacterial cells were consistently ovoid or round; under those conditions the addition of a second study antibiotic resulted in marked synergistic inhibition and killing which was independent of inoculum size and susceptibility to the second antibiotic. In contrast, synergy with mecillinam against mecillinam-susceptible strains or with other antibiotic combinations against any species was not consistently observed.