Meropenem pharmacokinetics in critically ill patients with or without burn treated with or without continuous veno-venous haemofiltration.

Autor: Selig DJ; Walter Reed Army Institute of Research, Experimental Therapeutics, Silver Spring, MD, United States., Akers KS; Clinical Research Support Division, United States Army Institute of Surgical Research, San Antonio, TX, United States., Chung KK; Uniformed Services University of the Health Sciences, Bethesda, MD, United States., Pruskowski KA; Clinical Research Support Division, United States Army Institute of Surgical Research, San Antonio, TX, United States., Livezey JR; Uniformed Services University of the Health Sciences, Bethesda, MD, United States., Por ED; Walter Reed Army Institute of Research, Experimental Therapeutics, Silver Spring, MD, United States.
Jazyk: angličtina
Zdroj: British journal of clinical pharmacology [Br J Clin Pharmacol] 2022 May; Vol. 88 (5), pp. 2156-2168. Date of Electronic Publication: 2021 Dec 09.
DOI: 10.1111/bcp.15138
Abstrakt: Introduction: Severe burn injury involves widespread skin and tissue damage leading to systemic inflammation, hypermetabolism and multi-organ failure. The hypermetabolic phase of burn injury has been associated with increased systemic antibiotic clearance; however, critical illness in the absence of burn may also induce similar physiologic changes. Continuous renal replacement therapy (CRRT) is often implemented in critically ill patients and may also affect antibiotic clearance. Although the pharmacokinetics (PK) of meropenem has been described in both the burn and non-burn critically ill populations, direct comparative data is lacking.
Methods: For this study, we evaluated PK parameters of meropenem from 23 critically ill patients, burn or non-burn, treated with or without continuous veno-venous haemofiltration (CVVH) to determine the contribution of burn and CVVH to the variability of therapeutic meropenem levels.
Results: A two-compartment model best described the data and revealed creatinine clearance (CrCl) and total burn surface area (TBSA) as significant covariates on clearance (CL) and peripheral volume of distribution (Vp), respectively. Of interest, non-burn patients on CVVH displayed an overall lower inherent CL as compared to burn patients on CVVH (6.43 vs. 12.85 L/h). Probability of target attainment (PTA) simulations revealed augmented renal clearance (ARC) may necessitate dose adjustments, but TBSA and CVVH would not.
Conclusions: We recommend a standard dose of 1000 mg every 8 hours; however, if ARC is suspected, or the severity of illness requires a more stringent therapeutic target, we recommend a loading dose of 1000-2000 mg infused over 30 minutes to 1 hour followed by continuous infusion (3000-6000 mg over 24 hours), or intermittent infusion of 2000 mg every 8 hours.
(Published 2021. This article is a U.S. Government work and is in the public domain in the USA. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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