Paradoxical antibacterial activities of beta-lactams against Proteus vulgaris: mechanism of the paradoxical effect.
Fifteen beta-lactam antibiotics were divided into four classes based on their antibacterial actions and beta-lactamase-inducing activities in Proteus vulgaris. One of these groups, which included cefmenoxime, ceftriaxone, cefuzonam, and cefotaxime, showed a clear paradoxical antibacterial activity against P. vulgaris. This group showed growth-inhibitory activity at relatively low concentrations, up to certain limits. These cephalosporins have, as a common moiety, an aminothiazolyl-oxyimino group in the 7-acyl side chain and have high beta-lactamase-inducing activities and low stabilities against the beta-lactamase. In a mutant strain incapable of inducing beta-lactamase, however, the paradoxical antibacterial activity was not observed. These findings suggest that beta-lactamase plays an essential role in the paradoxical antibacterial effect in P. vulgaris. We conclude that the induction of a large amount of beta-lactamase and the low stability against beta-lactamase may account for the paradoxical antibacterial activity in P. vulgaris.
Ikeda
Y
Y
Department of Microbiology, Kyoto Pharmaceutical University, Japan.
Nishino
T
T
D000900:Anti-Bacterial Agents / Q000145:classification / Q000494:pharmacology*; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D011485:Protein Binding; D011514:Proteus vulgaris / Q000187:drug effects* / Q000201:enzymology; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D019818:Clavulanic Acid; D001618:beta-Lactamases