Activities of trovafloxacin and ampicillin-sulbactam alone or in combination versus three strains of vancomycin-intermediate Staphylococcus aureus in an in vitro pharmacodynamic infection model

The recent isolation of clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) with intermediate susceptibility (MICs, 8 mu g/ml) to vancomycin (vancomycin-intermediate S. aureus [VISA]) emphasizes the importance of developing novel antimicrobial regimens and/or agents for future treatment. We studied the activities of ampicillin-sulbactam and trovafloxacin alone or in combination against three unique strains of VISA in an in vitro infection model. Two VISA strains were trovafloxacin susceptible (MICs, less than or equal to 2 mu g/ml); one VISA strain was trovaffoxacin resistant (MIC, 4 mu g/ml), Trovafloxacin was administered to simulate a dose of 200 or 400 mg every 24 h, Ampicillin sulbactam was administered to simulate a dose of 3 g every 6 h, Samples were removed from the infection models over 48 h, and reductions in colony counts were compared between regimens. Trovafloxacin (200 mg) produced rapid killing of a control MRSA strain over the 48-h experiment but produced only slight killing of all three VISA strains. The higher dose of trovafloxacin improved killing but did not produce bactericidal activity at 48 h, Ampicillin-sulbactam produced rapid bactericidal activity against all four strains tested, and colony counts at 8 h were at the limits of detection. However, regrowth occurred by 48 h for each strain. The combination of ampicillin-sulbactam and trovaffoxacin provided additive activity against two of the three VISA strains. In conclusion, trovaffoxacin or ampicillin-sulbactam alone did not provide adequate activity against the VISA strains for the 48-h evaluation period, but the combination could help improve activity against some strains of VISA.