Efficacy and safety of moxifloxacin for community-acquired bacterial pneumonia based on pharmacokinetic analysis

Moxifloxacin is a respiratory quinolone that is expected to be useful for treating community-acquired bacterial pneumonia, but few clinical studies and not a detailed evaluation of its pharmacokinetics have been conducted in Japan in patients with pneumonia. We assessed the efficacy and safety of moxifloxacin in 18 patients with community-acquired bacterial pneumonia using pharmacokinetic–pharmacodynamic analysis. There was significant improvement in body temperature, white blood cell count, C-reactive protein, and chest X-ray score on day 3 of moxifloxacin treatment, which persisted until the completion of treatment (all p < 0.05). Nine strains, including Streptococcus pneumoniae , Moraxella catarrhalis , Haemophilus influenzae , and Enterobacter cloacae , were isolated from sputum cultures of nine patients. The isolated strains were eradicated by moxifloxacin. The mean area under the concentration–time curve from 0 to 24 hours [AUC 0–24 h (AUC 0–24 h,ss )], maximum plasma concentration (C max ), and trough plasma level (C trough ) of moxifloxacin at steady state was 52.0 μg h/ml, 4.5, and 0.9 μg/ml, respectively. Mean AUC 0–24 h,ss /mimimum inhibitory concentration (MIC), and C max /MIC ratios for patients in whom MICs of moxifloxacin were determined for pathogenic bacteria were 723 and 62, respectively. The median AUC 0–24 h,ss /MIC and C max /MIC ratios (based on Monte Carlo simulation employing MICs for 257 strains of S. pneumoniae collected during a respiratory infection survey by the Japanese Society of Chemotherapy in 2007) were 209.56 and 17.88, respectively. Thus, when the target for the AUC/MIC ratio was set at ≥30 and that for the C max /MIC ratio at ≥5, the achievement rate for these two parameters was 97.36% and 96.71%, respectively. Two patients (11%) experienced three adverse effects [one nausea, another increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], but the events were not serious. Based on these results, moxifloxacin (400 mg once daily) was considered useful for treating community-acquired bacterial pneumonia and is expected to show excellent efficacy and safety as well as suppressing the emergence of resistance.