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

Abstract

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.