Pharmacokinetics of linezolid in critically ill patients on continuous renal replacement therapy: Influence of residual renal function on PK/PD target attainment


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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<10mL/min), the contribution of extracorporeal Cl to total Cl was higher (47% vs 16%) than in patients with residual renal function (CrCl≥10mL/min). For an MIC of 2mg/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 (600mg q12h) ensures a moderately high probability of treatment success in anuric patients when the infection is due to microorganisms with MIC≤2mg/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 900mg q8h provide higher probability of treatment success without compromising the safety.HIGHLIGHTSIn acute renal failure, CRRT conditions the total clearance of linezolid.The contribution of extracorporeal to total clearance is 3 times higher in anurics.For MIC≤2mg/L, 600mg q12h provide high probability of success in anuric patients.600mg q12h is deficient for patients with residual renal function receiving CRRT.900mg q8h improve the probability of success in nonanuric patients receiving CRRT.

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