Efficacy of Amoxycillin and Benzylpenicillin Combined with Clavulanic Acid against Bacteroides Fragilis in Vitro and in Experimentally Infected Mice

Abstract

Because the insensitivity of Bacteroides fragilis to penicillins is due to betalactamase formation, the potentiating effect of the betalactamase inhibitor clavulanic acid on the action of amoxycillin and benzylpenicillin against this bacterium was studied in vitro and in an experimental infection in mice. The addition of clavulanic acid to amoxycillin and benzylpenicillin resulted in a marked synergistic effect against B. fragilis, as assessed by both MIC determinations and in 4-h growth curves. In the experimental infection, where co-inoculation with Escherichia coli was obligatory for the outgrowth of B. fragilis, both penicillins had a dose-dependent effect on both species. However, the addition of clavulanic acid to amoxycillin and benzylpenicillin did not increase the effect of the penicillins against B. fragilis or against E. coli. Because a synergistic effect might have remained undetected in vivo, the experimental conditions were varied, i.e. the drugs were administered in the proliferation phase of B. fragilis, the clavulanic acid to betalactam ratios were varied, and the drugs were given after inoculation of B. fragilis in which betalactamase production has been induced. However, even after variation of the experimental conditions the addition of clavulanic acid to benzylpenicillin did not result in a potentiation of the effect of benzylpenicillin against B. fragilis.