Efficacy of ampicillin plus a beta-lactamase inhibitor (CP-45,899) in experimental endocarditis due to Staphylococcus aureus

Abstract

The efficacy of combined therapy with ampicillin and a beta-lactamase inhibitor, CP-45,899, for experimental endocarditis due to Staphylococcus aureus was evaluated. Three strains of beta-lactamase-producing S. aureus were used, and intramuscular doses of antibiotics were selected to produce serum levels in rabbits similar to those expected in humans. Sera from animals treated with ampicillin plus CP-45,899, but not from those treated with nafcillin plus gentamicin, had bactericidal activity against two nafcillin-resistant strains of S. aureus at 1 hr. The combination of ampicillin plus CP-45,899 was as effective as nafcillin in treatment of endocarditis due to one nafcillin-sensitive strain and was superior to nafcillin against two nafcillin-resistant strains (P less than 0.001). In a short-term treatment experiment using the nafcillin-sensitive strain, ampicillin plus CP-45,899 sterilized vegetations as rapidly as nafcillin plus gentamicin. Thus, ampicillin plus a beta-lactamase inhibitor may be effective treatment for bacteremic infections due to S. aureus, even when the strain is nafcillin-resistant.