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Synergistic activity of gentamicin, ciprofloxacin, and levofloxacin in combination with cefepime and piperacillin/tazobactam against P aeruginosa



Synergistic activity of gentamicin, ciprofloxacin, and levofloxacin in combination with cefepime and piperacillin/tazobactam against P aeruginosa



Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 41: 170-171



Background: A beta-lactam plus an aminoglycoside is the gold standard for treating P. aeruginosa infections. However, the fluoroquinolones are safer and may be an alternative to the aminoglycoside. In this study, the in vitro synergistic activity of gentamicin, cipro, and levo in combination with cefepime and piperacillin/tazobactam was evaluated against P. aeruginosa. Method: MICs were performed using NCCLS guidelines against 12 non-duplicate clinical isolates of P. aeruginosa. Time-kill studies were performed against each isolate with the following agents and concentrations (mug/mL) alone and in combination: cipro (1), levo (2), gentamicin (4), piperacillin/tazobactam (40/5), and cefepime (20). These concentrations represent achievable in vivo concentrations based on an AUC0-24 from typical dosing regimens. Bacterial densities were determined at 0, 2, 4, 6, 8, 12, and 24 hrs with synergy defined as >2 log reduction in killing at 24 hrs compared to the most active agent alone. Result: MICs (mug/mL) were: gentamicin (1-16), cipro (0.06-8), levo (0.5-16), cefepime (2-32), and piperacillin/tazobactam (4-256). None of the combinations were antagonistic. Although no statistical differences exist between the aminoglycoside and fluoroquinolone combinations (83% vs 71%, p=0.387), gentamicin combinations killed significantly faster than the fluoroquinolone combinations (time to 99.9% killing, 4.9 vs 9.3 hrs, p=0.003). Furthermore, no differences in synergistic activity were noted among the cipro combinations (67%) and levo combinations (75%). However, a statistically significant difference was observed between the beta-lactams (cefepime combinations 86% vs piperacillin/tazobactam 64%, p=0.030). Conclusion: No difference in synergy exist between aminoglycoside and fluoroquinolones when combination with a beta-lactam against P. aeruginosa. In vivo studies are necessary to evaluate the clinical outcomes of these combination regimens.

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