Moxifloxacin pharmacokinetic profile and efficacy evaluation in empiric treatment of community-acquired pneumonia
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Moxifloxacin pharmacokinetic profile and efficacy evaluation in empiric treatment of community-acquired pneumonia. / Öbrink-Hansen, Kristina; Hardlei, Tore Forsingdal; Brock, Birgitte; Jensen-Fangel, Søren; Kragh Thomsen, Marianne; Petersen, Eskild; Kreilgaard, Mads.
I: Antimicrobial Agents and Chemotherapy, Bind 59, Nr. 4, 04.2015, s. 2398-404.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Moxifloxacin pharmacokinetic profile and efficacy evaluation in empiric treatment of community-acquired pneumonia
AU - Öbrink-Hansen, Kristina
AU - Hardlei, Tore Forsingdal
AU - Brock, Birgitte
AU - Jensen-Fangel, Søren
AU - Kragh Thomsen, Marianne
AU - Petersen, Eskild
AU - Kreilgaard, Mads
N1 - Copyright © 2015, American Society for Microbiology. All Rights Reserved.
PY - 2015/4
Y1 - 2015/4
N2 - 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.).
AB - 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.).
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Anti-Bacterial Agents
KW - Area Under Curve
KW - Chromatography, High Pressure Liquid
KW - Community-Acquired Infections
KW - Computer Simulation
KW - Female
KW - Fluoroquinolones
KW - Humans
KW - Male
KW - Microbial Sensitivity Tests
KW - Middle Aged
KW - Models, Statistical
KW - Pneumonia
KW - Young Adult
U2 - 10.1128/AAC.04659-14
DO - 10.1128/AAC.04659-14
M3 - Journal article
C2 - 25666151
VL - 59
SP - 2398
EP - 2404
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 4
ER -
ID: 161867962