The role of beta-lactamase in mixed infections in mice in relation to treatment with ampicillin

Beta-lactamase-producing Staphylococcus aureus and Bacteroides fragilis in a localized mixed infection has been found to degrade the beta-lactam antibiotic at the focus of infection, thus protecting both the bacteria and pathogens susceptible to the antibiotic. To determine if beta-lactamase produced by Hemophilus influenzae and Branhamella catarrhalis have similar importance in mixed infections, a thread infection model in mice was used to evaluate the capacity of beta-lactamase produced by S. aureus, B. catarrhalis, or H. influenzae to hydrolyze ampicillin in a mixed infection with Streptococcus pneumoniae in mice. For both S. aureus and B. catarrhalis, the ampicillin concentrations at infection sites where beta-lactamase was produced were lower than at sites where beta-lactamase was not produced; however, this difference was not found when clavulanic acid was added to the ampicillin. In mixed infections with strains that did not produce beta-lactamase, ampicillin concentrations were similar with or without clavulanic acid. S. aureus was the best "protector" followed by B. catarrhalis. The beta-lactamase produced by H. influenzae failed to protect the S. pneumoniae. No bactericidal effect of clavulanic acid was found.