Helena Barrasa1, Amaia Soraluce2, Arantxazu Isla2, Alejandro Martín1, Javier Maynar1, Andrés Canut3, José Angel Sánchez-Izquierdo4, Alicia Rodríguez-Gascón5. 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; Centro de Investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Avenida Miguel de Unamuno, 3, Vitoria-Gasteiz, Spain. 3. Microbiology Service, University Hospital Araba, C/ Francisco Leandro de Viana n° 1, Vitoria-Gasteiz, Spain. 4. Intensive Care Unit, Doce de Octubre Hospital, Avda de Córdoba s/n, Madrid, Spain. 5. 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; Centro de Investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Avenida Miguel de Unamuno, 3, Vitoria-Gasteiz, Spain. Electronic address: alicia.rodriguez@ehu.eus.
Abstract
PURPOSE: To assess the pharmacokinetics of linezolid in septic patients undergoing continuous renal replacement therapy (CRRT) and investigate whether residual renal function affects the probability of attaining the pharmacokinetic/pharmacodynamic (PK/PD) target. MATERIAL AND METHODS: Prospective study conducted in three Spanish hospitals. Linezolid concentrations were measured in plasma and effluent samples and pharmacokinetic parameters were calculated. The probability of target attainment (PTA) and the cumulative fraction of response (CFR) were calculated considering AUC24/MIC>80 and %T>MIC > 85% as the PK/PD indexes related to efficacy. RESULTS: In anuric patients (CrCl<10 mL/min), the contribution of extracorporeal Cl to total Cl was higher (47% vs 16%) than in patients with residual renal function (CrCl≥10 mL/min). For an MIC of 2 mg/L, AUC24/MIC>80 was achieved in >85% of the anuric patients, but in <15% of the patients with residual renal function. CONCLUSIONS: The standard dose (600 mg q12h) ensures a moderately high probability of treatment success in anuric patients when the infection is due to microorganisms with MIC≤2 mg/L; although higher doses increase the probability of treatment success, the safety is compromised. In patients with residual renal function, the standard dose is insufficient, but 900 mg q8h provide higher probability of treatment success without compromising the safety.
PURPOSE: To assess the pharmacokinetics of linezolid in septicpatients undergoing continuous renal replacement therapy (CRRT) and investigate whether residual renal function affects the probability of attaining the pharmacokinetic/pharmacodynamic (PK/PD) target. MATERIAL AND METHODS: Prospective study conducted in three Spanish hospitals. Linezolid concentrations were measured in plasma and effluent samples and pharmacokinetic parameters were calculated. The probability of target attainment (PTA) and the cumulative fraction of response (CFR) were calculated considering AUC24/MIC>80 and %T>MIC > 85% as the PK/PD indexes related to efficacy. RESULTS: In anuric patients (CrCl<10 mL/min), the contribution of extracorporeal Cl to total Cl was higher (47% vs 16%) than in patients with residual renal function (CrCl≥10 mL/min). For an MIC of 2 mg/L, AUC24/MIC>80 was achieved in >85% of the anuric patients, but in <15% of the patients with residual renal function. CONCLUSIONS: The standard dose (600 mg q12h) ensures a moderately high probability of treatment success in anuric patients when the infection is due to microorganisms with MIC≤2 mg/L; although higher doses increase the probability of treatment success, the safety is compromised. In patients with residual renal function, the standard dose is insufficient, but 900 mg q8h provide higher probability of treatment success without compromising the safety.
Authors: Alison L Blackman; Praneeth Jarugula; David P Nicolau; Sai Ho Chui; Manjari Joshi; Emily L Heil; Mathangi Gopalakrishnan Journal: Antimicrob Agents Chemother Date: 2021-01-20 Impact factor: 5.191
Authors: Jason A Roberts; Rinaldo Bellomo; Menino O Cotta; Birgit C P Koch; Haifa Lyster; Marlies Ostermann; Claire Roger; Kiran Shekar; Kevin Watt; Mohd H Abdul-Aziz Journal: Intensive Care Med Date: 2022-08-23 Impact factor: 41.787