The Role of -Lactamase in Mixed Infections in Mice in Relation to Treatment with Ampicillin

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Abstract
β-lactamase-producing Staphylococcus aureus and Bacteroides fragilis in a localized mixed infection has been found to degrade the β-lactam antibiotic at the focus of infection, thus protecting both the bacteria and pathogens susceptible to the antibiotic. To determine if β-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 β-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. catarrhatis, the ampicillin concentrations at infection sites where β-lactamase was produced were lower than at sites where β-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 β-lactamase, ampicillin concentrations were similar with or without clavulanic acid. S. aureus was the best “protector” followed by B. catarrhatis. The β-lactamase produced by H. influenzae failed to protect the S. pneumoniae. No bactericidal effect of clavulanic acid was found.

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