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

The recent isolation of clinical strains of methicillin-resistant Staphyloc occus aureus (MRSA) with intermediate susceptibility (MICs, 8 mu g/ml) to v ancomycin (vancomycin-intermediate S. aureus [VISA]) emphasizes the importa nce of developing novel antimicrobial regimens and/or agents for future tre atment. We studied the activities of ampicillin-sulbactam and trovafloxacin alone or in combination against three unique strains of VISA in an in vitr o infection model. Two VISA strains were trovafloxacin susceptible (MICs, l ess than or equal to 2 mu g/ml); one VISA strain was trovaffoxacin resistan t (MIC, 4 mu g/ml), Trovafloxacin was administered to simulate a dose of 20 0 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. Trov afloxacin (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 bac tericidal activity at 48 h, Ampicillin-sulbactam produced rapid bactericida l activity against all four strains tested, and colony counts at 8 h were a t the limits of detection. However, regrowth occurred by 48 h for each stra in. The combination of ampicillin-sulbactam and trovaffoxacin provided addi tive activity against two of the three VISA strains. In conclusion, trovaff oxacin or ampicillin-sulbactam alone did not provide adequate activity agai nst the VISA strains for the 48-h evaluation period, but the combination co uld help improve activity against some strains of VISA.