High doses of levofloxacin vs moxifloxacin against staphylococcal experimental foreign-body infection: The effect of higher MIC-related pharmacokinetic parameters on efficacy

SummaryObjectivesSince levofloxacin at high doses was the best therapy in staphylococcal tissue-cage model of foreign-body infection, we hypothesized that moxifloxacin with higher ratio of area under the concentration–time curve to the MIC (AUC/MIC) would provide better results.MethodsMICs, MBCs, MPCs (mutant prevention concentration) and 24 h kill-curves were determined in the log and stationary phases. Using the aforementioned model, we tested the efficacy of levofloxacin 100 mg/kg/d, moxifloxacin 40 mg/kg/d and moxifloxacin 80 mg/kg/d; they were equivalent to human levels for 1000 mg/d, 400 mg/d and 800 mg/d, respectively. We screened for the appearance of resistant strains.ResultsMICs and MBCs in logarithmic and stationary phases and MPCs of levofloxacin were 0.5, 1 and 4, 0.8 μg/ml, respectively, and those of moxifloxacin 0.12, 0.25 and 2, 0.25 μg/ml. AUC/MIC were 234 (levofloxacin), 431 (moxifloxacin 40) and 568 (moxifloxacin 80). Bacterial counts decreases in tissue-cage fluids (means of log CFU/ml) were −1.81 (n = 25), −1.31 (23), and −1.46 (20), respectively; for controls it was 0.24 (22). All groups were better than controls (p < 0.05); no differences between them existed.ConclusionsMoxifloxacin with higher AUC/MIC ratio did not improve the efficacy of high doses of levofloxacin.