Failure of target attainment of beta-lactam antibiotics in critically ill patients and associated risk factors: a two-center prospective study (EXPAT)

Critical Care

Teun van Gelder¹  Soma Bahmany²  Alan Abdulla²  Birgit C. P. Koch²  Nicole G. M. Hunfeld³  Diederik Gommers⁴  Henrik Endeman⁴  Tim M. J. Ewoldt⁴  Annemieke Dijkstra⁵  Anouk E. Muller⁶ 

[1] Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands;Department of Hospital Pharmacy, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, the Netherlands;Department of Hospital Pharmacy, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, the Netherlands;Department of Intensive Care, Erasmus University Medical Center, Rotterdam, The Netherlands;Department of Intensive Care, Erasmus University Medical Center, Rotterdam, The Netherlands;Department of Intensive Care, Maasstad Hospital, Rotterdam, The Netherlands;Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands;Department of Medical Microbiology, Haaglanden Medical Center, The Hague, The Netherlands;

关键词: Beta-lactam;    Critically ill patients;    Pharmacokinetics;    Pharmacodynamics;    Target attainment;    Risk factors;   

DOI  :  10.1186/s13054-020-03272-z

来源: Springer

【 摘 要 】

BackgroundEarly and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic dosing is not suitable in critically ill patients, since these patients undergo physiological alterations that strongly affect antibiotic exposure. For beta-lactam antibiotics, the unbound plasma concentrations above at least one to four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval (100%ƒT > 1–4×MIC) have been proposed as pharmacodynamic targets (PDTs) to maximize bacteriological and clinical responses. The objectives of this study are to describe the PDT attainment in critically ill patients and to identify risk factors for target non-attainment.MethodsThis prospective observational study was performed in two ICUs in the Netherlands. We enrolled adult patients treated with the following beta-lactam antibiotics: amoxicillin (with or without clavulanic acid), cefotaxime, ceftazidime, ceftriaxone, cefuroxime, and meropenem. Based on five samples within a dosing interval at day 2 of therapy, the time unbound concentrations above the epidemiological cut-off (ƒT > MICECOFF and ƒT > 4×MICECOFF) were determined. Secondary endpoints were estimated multivariate binomial and binary logistic regression models, for examining the association of PDT attainment with patient characteristics and clinical outcomes.ResultsA total of 147 patients were included, of whom 63.3% achieved PDT of 100%ƒT > MICECOFF and 36.7% achieved 100%ƒT > 4×MICECOFF. Regression analysis identified male gender, estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2, and high body mass index (BMI) as risk factors for target non-attainment. Use of continuous renal replacement therapy (CRRT) and high serum urea significantly increased the probability of target attainment. In addition, we found a significant association between the 100%ƒT > MICECOFF target attainment and ICU length of stay (LOS), but no significant correlation was found for the 30-day survival.ConclusionsTraditional beta-lactam dosing results in low target attainment in the majority of critically ill patients. Male gender, high BMI, and high eGFR were significant risk factors for target non-attainment. These predictors, together with therapeutic drug monitoring, may help ICU clinicians in optimizing beta-lactam dosing in critically ill patients.Trial registrationNetherlands Trial Registry (EXPAT trial), NTR 5632. Registered on 7 December 2015.

【 授权许可】

CC BY