Optimal levofloxacin dosing regimens in critically ill patients with acute kidney injury receiving continuous renal replacement therapy

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Research Article: Optimal levofloxacin dosing regimens in critically ill patients with acute kidney injury receiving continuous renal replacement therapy
Author: Dhakrit Rungkitwattanakula, Weerachai Chaijamornb, Taniya Charoensareeratb, Pratarn Charntrakarnc, Orapan Khamkampudd, Nakumporn Rattanaponpaserte, Nattachai Srisawatfghijk, Sutthiporn Pattharachayaku
Email: weerachai.cha@siam.edu
Department/Faculty Faculty of Pharmacy,  Siam University, Bangkok 10160
Published: Journal of Critical Care, Volume 63, June 2021, Pages 154-160

Citation

Dhakrit Rungkitwattanakula, Weerachai Chaijamornb, Taniya haroensareeratb, Pratarn Charntrakarnc, Orapan Khamkampudd, Nakumporn Rattanaponpaserte, Nattachai Srisawatfghijk, Sutthiporn Pattharachayaku. (2021). Optimal levofloxacin dosing regimens in critically ill patients with acute kidney injury receiving continuous renal replacement therapy, Journal of Critical Care, 63(June),  154-160. https://doi.org/10.1016/j.jcrc.2020.09.018


ABSTRACT

Purposes: To determine appropriate dosing of levofloxacin in critically ill patients receiving continuous renal replacement therapy (CRRT).

Methods: All necessary pharmacokinetic and pharmacodynamic parameters from critically ill patients were obtained to develop mathematical models with first order elimination. Levofloxacin concentration-time profiles were calculated to determine the efficacy based on the probability of target attainment (PTA) of AUC24h/MIC ≥50 for Gram-positive and AUC24h/MIC ≥125 for Gram-negative infections. A group of 5000 virtual patients was simulated and tested using Monte Carlo simulations for each dose in the models. The optimal dosing regimens were defined as the dose achieved target PTA at least 90% of the virtual patients.

Results: No conventional, FDA approved regimens achieved at least 90% of PTA for Gram-negative infection with Pseudomonas aeruginosa at MIC of 2 mg/L. The successful dose (1750 mg on day 1, then 1500 mg q 24 h) was far exceeded the maximum FDA-approved doses. For Gram-positive infections, a levofloxacin 750 mg q 24 h was sufficient to attain PTA target of ~90% at the MIC of 2 mg/L for Streptococcus pneumoniae.

Conclusions: Levofloxacin cannot be recommended as an empiric monotherapy for serious Gram-negative infections in patients receiving CRRT due to suboptimal efficacy.

Keywords: Levofloxacin Continuous renal replacement therapy, Critically ill patients, Monte Carlo simulations, Drug dosing.


Optimal levofloxacin dosing regimens in critically ill patients with acute kidney injury receiving continuous renal replacement therapy

Faculty of Pharmacy, Siam University, Bangkok, Thailand

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