Laboratory Tests for Defining Bactericidal Activity as Predictors of Antibiotic Efficacy in the Treatment of Endocarditis Due to Staphylococcus aureus in Rabbits

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Abstract
The validity of laboratory tests that define bactericidal activity to predict antimicrobial efficacy was studied in rabbits with endocarditis due to Staphylococcus aureus, both nafcillin-nontolerant (NT) and nafcillin-tolerant (T). Infected rabbits were treated with nafcillin, clindamycin, chloramphenicol, or no drug (control) for up to 11 days; dosage was designed so that peak antibiotic serum concentration/minimal inhibitory concentration ratios were ∼50. During treatment, peak and trough serum concentration/minimal bactericidal concentration ratios and peak and trough titers of serum bactericidal antibacterial activity were determined. The rank order of efficacy, as defined by survival, eradication of bacteremia, and sterilization of cardiac vegetations, was nafcillin = clindamycin > chloramphenicol > control, both adjusted and unadjusted for the challenge strain of S. aureus. Bactericidal activity (observed only with nafcillin plus S. aureus NT) was associated with lower bacterial counts in vegetations at four days but was otherwise unrelated to therapeutic outcome.