Optimal levofloxacin dosing regimens in critically ill patients with acute kidney injury receiving continuous renal replacement therapy |
| |
| Institution: | 1. Department of Pharmacy Practice, Faculty of Pharmaceutical Science, Chulalongkorn University, Bangkok 10330, Thailand;2. Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand;3. Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;4. Faculty of Pharmacy, Siam University, Bangkok 10160, Thailand;5. Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;1. Intensive Care Unit, University Hospital Araba C/ Olaguibel n° 29, Vitoria-Gasteiz, Spain;2. Pharmacokinetics, Nanotechnology and Gene Therapy Group, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad n° 7, Vitoria-Gasteiz, Spain;3. Centro de Investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Avenida Miguel de Unamuno, 3, Vitoria-Gasteiz, Spain;4. Microbiology Service, University Hospital Araba, C/ Francisco Leandro de Viana n° 1, Vitoria-Gasteiz, Spain;5. Intensive Care Unit, Doce de Octubre Hospital, Avda de Córdoba s/n, Madrid, Spain;1. University of Queensland Centre of Clinical Research, Faculty of Medicine, University of Queensland, Brisbane, Australia;2. Queensland University of Technology, School of Nursing, Brisbane, Queensland, Australia;3. Department of Intensive Care Medicine, Royal Brisbane and Women''s Hospital, Herston, Queensland, Australia;4. School of Medicine, University of Queensland, Brisbane, Queensland, Australia;5. Department of Pharmacy, Royal Brisbane and Women''s Hospital, Brisbane, Queensland, Australia;6. Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, University of Queensland, Brisbane, Queensland, Australia;7. Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France |
| |
| Abstract: | PurposesTo determine appropriate dosing of levofloxacin in critically ill patients receiving continuous renal replacement therapy (CRRT).MethodsAll 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.ResultsNo 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.ConclusionsLevofloxacin cannot be recommended as an empiric monotherapy for serious Gram-negative infections in patients receiving CRRT due to suboptimal efficacy. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
