title: 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.
abstract: The recent isolation of clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) with intermediate susceptibility (MICs, 8 microg/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, < or =2 microg/ml); one VISA strain was trovafloxacin resistant (MIC, 4 microg/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 trovafloxacin provided additive activity against two of the three VISA strains. In conclusion, trovafloxacin 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.
authors.affiliation: The Anti-Infective Research Laboratory, Department of Pharmacy Services, Detroit Receiving Hospital and University Health Center, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Aeschlimann
authors.forename: E
authors.initials: E
authors.lastname: Hershberger
authors.forename: M J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000667:Ampicillin / Q000493:pharmacokinetics / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000494:pharmacology*; D024841:Fluoroquinolones; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D013407:Sulbactam / Q000493:pharmacokinetics* / Q000494:pharmacology; D020713:Vancomycin Resistance
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D000667:Ampicillin; C080163:trovafloxacin; D013407:Sulbactam