PHARMACODYNAMICS OF BETA-LACTAM ANTIBIOTICS ON GRAM-NEGATIVE BACTERIA - INITIAL KILLING, MORPHOLOGY AND POSTANTIBIOTIC EFFECT

The aim of this study was to investigate the pharmacodynamics of beta-lactam antibiotics on Gram-negative bacteria by studying the in vitro postantibiotic effect (PAE), initial killing and morphology. The PAE of aztreonam, cefotaxime, ceftazidime, imipenem, mecillinam and piperacillin on Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens was studied by use of bioluminescence assay of bacterial ATP. The strains were exposed for 2 h to the beta-lactam antibiotics which were then eliminated by 10(-4) dilution. With E. coli, spheroplasts were seen during incubation with cefotaxime, ceftazidime, imipenem and mecillinam and a long (> 1 h) PAE was noted. In contrast, aztreonam and piperacillin produced a short (less-than-or-equal-to 1 h) PAE. This was seen concomitantly with the production of filaments and weak initial killing.