Estimated glomerular filtration rate as a tool for early identification of patients with insufficient exposure to beta-lactam antibiotics in intensive care units.

Autor: Damgaard T; Pharmaceutical Department in Kalmar, Region Kalmar County, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden., Woksepp H; Department of Research and Department of Clinical Microbiology in Kalmar, Region Kalmar County, and Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden., Brudin L; Department of Clinical Physiology in Kalmar, Region Kalmar County, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden., Bonnedahl J; Department of Infectious Diseases in Kalmar, Region Kalmar County, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden., Nielsen EI; Department of Pharmacy, Uppsala University, Uppsala, Sweden., Schön T; Department of Infectious Diseases in Kalmar, Region Kalmar County, Department of Infectious Diseases in Linköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden., Hällgren A; Department of Infectious Diseases in Linköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Jazyk: angličtina
Zdroj: Infectious diseases (London, England) [Infect Dis (Lond)] 2024 Jun; Vol. 56 (6), pp. 451-459. Date of Electronic Publication: 2024 Mar 04.
DOI: 10.1080/23744235.2024.2323002
Abstrakt: Background: Only about 50% of intensive care unit (ICU) patients reach a free trough concentration above MIC (100% fT > MIC) of beta-lactam antibiotics. Although dose adjustments based on therapeutic drug monitoring (TDM) could be beneficial, TDM is not widely available. We investigated serum creatinine-based estimated GFR (eGFR) as a rapid screening tool to identify ICU patients at risk of insufficient exposure.
Method: Ninety-three adult patients admitted to four ICUs in southeast Sweden treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Beta-lactam trough concentrations were measured. The concentration target was set to 100% fT > MIC ECOFF (2, 4, and 16 mg/L based on calculated free levels for meropenem, cefotaxime, and piperacillin, respectively). eGFR was primarily determined via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) and compared to three other eGFR equations. Data was analysed using logistic regression and receiver operative characteristic (ROC) curves.
Results: With intermittent standard dosing, insufficient exposure was common in patients with a relative eGFR ≥48mL/min/1.73m 2 [85%, (45/53)], particularly when treated with cefotaxime [96%, (24/25)]. This eGFR cut-off had a sensitivity of 92% and specificity of 82% (AUC 0.871, p  < 0.001) in identifying insufficient exposure. In contrast, patients with eGFR <48mL/min/1.73m 2 had high target attainment [90%, (36/40)] with a wide variability in drug exposure. There was no difference between the four eGFR equations (AUC 0.866-0.872, cut-offs 44-51 ml/min/1.73m 2 ).
Conclusion: Serum creatinine-based eGFR is a simple and widely available surrogate marker with potential for early identification of ICU patients at risk of insufficient exposure to piperacillin, meropenem, and cefotaxime.
Databáze: MEDLINE
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