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.