SYNERGISTIC EFFECT OF CEPHALEXIN WITH MECILLINAM

• Published in: Journal of antibiotics Vol. 34; no. 6; pp. 739 - 752
• Main Author: OTSUKI, MASAKO
• Format: Journal Article
• Language: English
• Published: Japan JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 01.01.1981
• Subjects: Amdinocillin - pharmacology; Amdinocillin - therapeutic use; Animals; Bacteria - drug effects; Bacterial Infections - drug therapy; Cephalexin - pharmacology; Cephalexin - therapeutic use; Drug Synergism; Drug Therapy, Combination; Escherichia coli - drug effects; Escherichia coli - ultrastructure; Male; Mice; Penicillanic Acid - pharmacology; Species Specificity
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.34.739

In vitro and in vivo synergistic effects of cephalexin and mecillinam against Escherichia coil, Klebsiella pneumoniae, Enterobacter sp., Serratia marcescens and Proteus sp. were demonstrated and their action mechanism were also discussed. The growth curve after the exposure of cephalexin and mecillinam at the concentrations at which these antibiotics had no effects when given alone showed a decrease of the turbidity and the presence of a bactericidal effect. In experimental infection in mice, the combination of both drugs showed a synergistic effect and excellent therapeutic effect. The blood concentration ratio of cephalexin to mecillinam was coincident with the concentration ratio of these antibiotics at which the synergistic effect was observed in vitro. Phase-contrast and scanning electron micrographs of bacterial cells exposed to the combination of cephalexin and mecillinam showed somewhat elongated bacteria and formation of spindle cells with swelling in the central part. A leakage of the cellular contents from part of the swelled cell wall was observed by transmission electron microscope. Cephalexin showed an affinity for penicillin binding proteins (PBPs)-1a and 3 in Escherichia coli and mecillinam showed an affinity for PBP-2. When these antibiotics were used concurrently, they exerted an additive effect to increase the affinity for PBPs. The lytic activity was increased much more after the combination of two antibiotics than after a single exposure.