Moxifloxacin Pharmacokinetic Profile and Efficacy Evaluation in Empiric Treatment of Community-Acquired Pneumonia

Abstract

ABSTRACTWhen antimicrobials are used empirically, pathogen MICs equal to clinical breakpoints or epidemiological cutoff values must be considered. This is to ensure that the most resistant pathogen subpopulation is appropriately targeted to prevent emergence of resistance. Accordingly, we determined the pharmacokinetic (PK) profile of moxifloxacin at 400 mg/day in 18 patients treated empirically for community-acquired pneumonia. We developed a population pharmacokinetic model to assess the potential efficacy of moxifloxacin and to simulate the maximal MICs for which recommended pharmacokinetic-pharmacodynamic (PK-PD) estimates are obtained. Moxifloxacin plasma concentrations were determined the day after therapy initiation using ultra-high-performance liquid chromatography. Peak drug concentrations (Cmax) and area under the free drug concentration-time curve from 0 to 24 h (fAUC0–24) values predicted for each patient were evaluated against epidemiological cutoff MIC values forStreptococcus pneumoniae,Haemophilus influenzae, andLegionella pneumophila. PK-PD targets adopted were aCmax/MIC of ≥12.2 for all pathogens, anfAUC0–24/MIC of >34 forS. pneumoniae, and anfAUC0–24/MIC of >75 forH. influenzaeandL. pneumophila. Individual predicted estimates forCmax/MIC andfAUC0–24/MIC as well as simulated maximal MICs resulting in target attainment for oral and intravenous administration of the drug were suitable forS. pneumoniaeandH. influenzaebut not forL. pneumophila. These results indicate that caution must be taken when moxifloxacin is used as monotherapy to treat community-acquired pneumonia caused byL. pneumophila. In conclusion, this report reveals key information relevant to the empirical treatment of community-acquired pneumonia while highlighting the robust and flexible nature of this population pharmacokinetic model to predict therapeutic success. (Clinical Trials Registration no. NCT01983839.)