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

Autor: Soma Bahmany, Diederik Gommers, Birgit C. P. Koch, Alan Abdulla, Nicole G. M. Hunfeld, Annemieke Dijkstra, Anouk E. Muller, Teun van Gelder, Henrik Endeman, Tim M J Ewoldt
Přispěvatelé: Pharmacy, Department of Psychology, Education and Child Studies, Intensive Care, Medical Microbiology & Infectious Diseases
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
medicine.medical_specialty
Time Factors
Critical Illness
medicine.medical_treatment
Beta-lactam
beta-Lactams
Critical Care and Intensive Care Medicine
Meropenem
Body Mass Index
03 medical and health sciences
0302 clinical medicine
Critically ill patients
Internal medicine
Odds Ratio
medicine
Humans
Pharmacokinetics
Prospective Studies
030212 general & internal medicine
Renal replacement therapy
Dosing
Prospective cohort study
Aged
Netherlands
0303 health sciences
medicine.diagnostic_test
030306 microbiology
business.industry
Research
lcsh:Medical emergencies. Critical care. Intensive care. First aid
lcsh:RC86-88.9
Middle Aged
Anti-Bacterial Agents
Logistic Models
Pharmacodynamics
Risk factors
Therapeutic drug monitoring
Ceftriaxone
Female
Drug Monitoring
Target attainment
business
Cefuroxime
medicine.drug
Zdroj: Critical Care, Vol 24, Iss 1, Pp 1-12 (2020)
Critical Care
Critical Care, 24(1):558. BioMed Central Ltd.
Critical Care, 24(1). BMC
ISSN: 1364-8535
1466-609X
DOI: 10.1186/s13054-020-03272-z
Popis: Background Early 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. Methods This 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. Results A 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. Conclusions Traditional 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 registration Netherlands Trial Registry (EXPAT trial), NTR 5632. Registered on 7 December 2015.
Databáze: OpenAIRE
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