title: Moxifloxacin pharmacokinetic profile and efficacy evaluation in empiric treatment of community-acquired pneumonia.
abstract: When 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 for Streptococcus pneumoniae, Haemophilus influenzae, and Legionella pneumophila. PK-PD targets adopted were a Cmax/MIC of ≥12.2 for all pathogens, an fAUC0-24/MIC of >34 for S. pneumoniae, and an fAUC0-24/MIC of >75 for H. influenzae and L. pneumophila. Individual predicted estimates for Cmax/MIC and fAUC0-24/MIC as well as simulated maximal MICs resulting in target attainment for oral and intravenous administration of the drug were suitable for S. pneumoniae and H. influenzae but not for L. pneumophila. These results indicate that caution must be taken when moxifloxacin is used as monotherapy to treat community-acquired pneumonia caused by L. 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.).
authors: Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark krisoebr@rm.dk.
authors: Kristina
authors: K
authors: Öbrink-Hansen
authors: Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark.
authors: Tore Forsingdal
authors: TF
authors: Hardlei
authors: Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark.
authors: Birgitte
authors: B
authors: Brock
authors: Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark.
authors: Søren
authors: S
authors: Jensen-Fangel
authors: Department of Clinical Microbiology, Aarhus University Hospital, Skejby, Denmark.
authors: Marianne
authors: M
authors: Kragh Thomsen
authors: Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark Department of Clinical Microbiology, Aarhus University Hospital, Skejby, Denmark.
authors: Eskild
authors: E
authors: Petersen
authors: Department of Drug Design and Pharmacology, University of Copenhagen, Denmark.
authors: Mads
authors: M
authors: Kreilgaard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology; D003198:Computer Simulation; D005260:Female; D024841:Fluoroquinolones / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015233:Models, Statistical; D000077266:Moxifloxacin; D011014:Pneumonia / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077266:Moxifloxacin