Open AccessClinical Pharmacodynamics of Meropenem in Patients with Lower Respiratory Tract Infections
Author(s) -
Chonghua Li,
Xin Du,
Joseph L. Kuti,
David P. Nicolau
Publication year - 2007
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00294-06
Subject(s) - pharmacodynamics , meropenem , pharmacokinetics , medicine , respiratory tract infections , antibiotics , area under the curve , dosing , minimum inhibitory concentration , population , ketolide , pharmacology , gastroenterology , antibacterial agent , respiratory system , microbiology and biotechnology , biology , antibiotic resistance , environmental health
Studies of β-lactam pharmacodynamics in infected patients are sparse. In this study, classification and regression tree (CART) and logistic regression analyses were used to identify which pharmacodynamic indices and magnitudes were significant predictors of meropenem efficacy for 101 adult patients with lower respiratory tract infections (LRTI). Using demographic data, a validated population pharmacokinetic model was employed to predict pharmacokinetic parameters and free serum concentrations in the studied patients. Pharmacodynamic indices [percentage of the dosing interval that free drug concentrations remain above the MIC (%fT > MIC),f (maximum concentration of drug in serum) (fC max )/MIC,fC min /MIC, andf (area under the concentration-time curve) (f AUC)/MIC] were calculated based on the baseline pathogen with the highest drug MIC for each patient. The median (range) of percentfT > MIC,fC max /MIC,fC min /MIC, andf AUC/MIC were 100% (0 to 100%), 728.8 (0.8 to 15,777), 19.9 (0.01 to 278), and 3,605.4 (2.7 to 60,865.9), respectively. CART identified the following breakpoints as significant predictors for microbiological response: >54%fT > MIC, afC max /MIC > 383, and afC min /MIC > 5;fC min /MIC > 5 was the only significant predictor of clinical response. Due to 100%fT > MIC achieved in the majority of LRTI patients,fC min /MIC was the statistically significant parameter associated with meropenem clinical and microbiological response in the adults with LRTI. The findings for LRTI patients can be applied to optimize meropenem dose regimens to achieve clinical success and microbiological eradication in clinical practice.