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

• Published in: Journal of critical care Vol. 63; pp. 154 - 160
• Main Authors: Rungkitwattanakul, Dhakrit, Chaijamorn, Weerachai, Charoensareerat, Taniya, Charntrakarn, Pratarn, Khamkampud, Orapan, Rattanaponpasert, Nakumporn, Srisawat, Nattachai, Pattharachayakul, Sutthiporn
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2021; Elsevier Limited
• Subjects: Antibiotics; Continuous renal replacement therapy; Critically ill patients; Dialysate; Drug dosages; Drug dosing; Effluents; Hemodialysis; Intensive care; Kidneys; Levofloxacin; Monte Carlo simulation; Monte Carlo simulations; Mortality; Pharmacodynamics; Pharmacokinetics; Pneumonia; Renal replacement therapy; Streptococcus infections; r2; Levofloxacin; Qplasma; Qreplacement; L; N; SA; Vd; AUC24h; SC; SD; min; gmol−1; Qblood; mg; kg; Continuous renal replacement therapy; AKI; CLSI; Quf; MIC; Critically ill patients; CVVHD; g; h; Drug dosing; CRRT; q; CLNR; Monte Carlo simulations; Qd; PD; CLHF; KDIGO; LD; CLHD; CVVH; PK; PTA; mL
• ISSN: 0883-9441; 1557-8615
• DOI: 10.1016/j.jcrc.2020.09.018

To determine appropriate dosing of levofloxacin in critically ill patients receiving continuous renal replacement therapy (CRRT). 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. 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. Levofloxacin cannot be recommended as an empiric monotherapy for serious Gram-negative infections in patients receiving CRRT due to suboptimal efficacy. •There are limited studies to examine the outcomes using pharmacokinetic and pharmacodynamic parameters of levofloxacin dosing regimens recommended in the literature for patients receving CRRT.•None of the FDA-approved maximal dose of levofloxacin or dosage for normal renal function were able to attain at least 90% PTA for managing Pseudomonas aeruginosa infections.•The highest FDA recommended dosing regimens would be effective for only Gram positive infections in critically ill patients receiving CRRT.•We recommed not using levofloxacin for the empirical therapy of Gram negative infection in seriously ill patients with CRRT.