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Antimicrobial Agents and Chemotherapy, May 2007, p. 1725-1730, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.00294-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Clinical Pharmacodynamics of Meropenem in Patients with Lower Respiratory Tract Infections{triangledown}

Chonghua Li, Xiaoli Du, Joseph L. Kuti, and David P. Nicolau*

Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut 06102

Received 8 March 2006/ Returned for modification 21 July 2006/ Accepted 11 February 2007

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) (fCmax)/MIC, fCmin/MIC, and f(area under the concentration-time curve) (fAUC)/MIC] were calculated based on the baseline pathogen with the highest drug MIC for each patient. The median (range) of percent fT > MIC, fCmax/MIC, fCmin/MIC, and fAUC/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, a fCmax/MIC > 383, and a fCmin/MIC > 5; fCmin/MIC > 5 was the only significant predictor of clinical response. Due to 100% fT > MIC achieved in the majority of LRTI patients, fCmin/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.

* Corresponding author. Mailing address: Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102. Phone: (860) 545-3941. Fax: (860) 545-3992. E-mail: dnicola{at}harthosp.org

{triangledown} Published ahead of print on 16 February 2007.

Antimicrobial Agents and Chemotherapy, May 2007, p. 1725-1730, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.00294-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Roberts, J. A., Kirkpatrick, C. M. J., Roberts, M. S., Robertson, T. A., Dalley, A. J., Lipman, J. (2009). Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother 64: 142-150 [Abstract] [Full Text]  


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