In vitro evaluation of the activity of two doses of Levofloxacin alone and in combination with other agents against Pseudomonas aeruginosa

P. aeruginosa is one of the most difficult to treat pathogens that generally requires combination therapy to prevent the development of resistance. This study evaluated the in vitro activity of two concentrations of levofloxacin (modeled for the 500 mg and 750 mg daily dose) in combination with ceftazidime, cefepime, piperacillin/tazobactam, imipenem, and tobramycin against P. aeruginosa. MICs and time-kill studies were performed against 12 non-duplicate clinical isolates of P. aeruginosa. The percent susceptible for levofloxacin, ceftazidime, cefepime, piperacillin/tazobactam, imipenem, and tobramycin were 67%, 58%, 58%, 67%, 75%, and 100%, respectively. Tobramycin was the most active single agent, killing and maintaining > or =99.9% killing over a 24 h period against all isolates. Levofloxacin 4 microg/mL(750 mg/day) alone reached 99.9% killing and maintain this killing over the time period more often than levofloxacin 2 microg/mL (500 mg/day). No combination was antagonistic and all combinations with tobramycin were indifferent. Overall, levofloxacin 2 microg/mL plus a beta-lactam was synergistic (65%) more often than levofloxacin 4 microg/mL combinations (46%). This was not unexpected due to the increased activity of levofloxacin 4 microg/mL. However, levofloxacin 4 microg/mL combinations maintained a > or =99.9% killing over the entire 24 h period more often than levofloxacin 2 microg/mL combinations (94% vs 83%). The findings from this work suggest that levofloxacin 750 mg/day in combination with another agent active against P. aeruginosa may prove to be clinically beneficial and superior to combinations using lower doses of levofloxacin. In vivo studies are needed to evaluate the clinical significance of these findings.