Optimal
therapy of
infections caused by borderline
oxacillin-susceptible,
beta-lactamase-hyperproducing Staphylococcus aureus has not been established. We used a rat model of aortic valve
endocarditis to examine efficacies of
antibiotic regimens against a borderline
oxacillin-susceptible strain as compared with a fully susceptible S. aureus strain. Animals were treated with
oxacillin alone or in combination with
sulbactam or with
ampicillin-sulbactam combinations at two dose levels.
Infections caused by the borderline susceptible and fully susceptible strains responded equally well to
oxacillin alone, with residual bacterial titers in vegetations falling to 4.8 +/- 1.6 and 4.4 +/- 1.7 (mean +/- standard deviation) log10 CFU/g, respectively. Addition of
sulbactam to
oxacillin (1:2) did not enhance the efficacy of
oxacillin against either strain in the animal model. A high-dose regimen of
ampicillin-sulbactam (2:1) yielding mean (+/- standard deviation) levels in serum of 16.8 +/- 7.4 and 9.5 +/- 1.1 micrograms/ml, respectively, proved equally effective against both strains (bacterial titers, 6.6 log10 CFU/g). However, at lower doses (8.3 +/- 2.6 and 5.9 +/- 2.4 micrograms/ml, the combination showed greater efficacy against the fully susceptible strain, with residual titers of 7.1 +/- 2.0 versus 9.0 +/- 1.6 log10 CFU/g (P less than 0.05). In vitro studies revealed that the
beta-lactamase inhibitor sulbactam was also a potent inducer of staphylococcal
beta-lactamase at clinically relevant concentrations. Based on this short-term in vivo
therapy study,
oxacillin would be predicted to be clinically effective in the
therapy of
infections caused by borderline
oxacillin-susceptible strains of S. aureus, while the combination of
ampicillin with
sulbactam appears to be inferior to
oxacillin alone against such
infections.