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Published on: November 27, 2019
Association between β-lactam concentration and liver injury in critically ill patients
Anita Farinella1, Federica Montanaro2, Michele Salvagno3
1Department of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium; Department of Anaesthesia and Intensive Care, Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione (IRCCS-ISMETT), Palermo, Italy.
Objective:
Therapeutic drug monitoring (TDM) may help optimize antibiotic dosing while minimizing toxicity in critically ill patients. This study investigated whether elevated plasma concentrations of β-lactam antibiotics, as assessed by TDM, were associated with an increased risk of liver injury in the ICU.
Methods:
We conducted a single-centre retrospective cohort study of patients in the ICU admitted to the Hôpital Universitaire de Bruxelles (2009-2014) who underwent TDM for β-lactam antibiotics. Total plasma trough concentrations (Co) were measured for piperacillin-tazobactam (PIP), meropenem, and ceftazidime/cefepime. Liver injury was identified via liver function tests on the day of TDM and classified into hepatocellular, cholestatic, or mixed patterns.
Results:
Among 425 patients in the ICU with β-lactam TDM, 154 (36.2%) developed liver injury, including hepatocellular (8.7%), cholestatic (22.1%), and mixed (5.4%) patterns. TDM was performed a median of 5 d after ICU admission and 2 d after antibiotic initiation. The overall Co for PIP, meropenem, and ceftazidime/cefepime were 37.8 (12.0-69.5), 4.5 (2.5-9.0), and 29.8 (18.7-47) mg/L, respectively. Patients with drug-induced liver injury had numerically higher β-lactam Co than patients without drug-induced liver injury; however, this difference was only statistically significant in patients treated with PIP (44.7 [23.4-76.7] vs. 30.6 [6.4-59.5]; P = 0.03). In a logistic regression analysis, Co was not independently associated with liver injury. Considering only patients that received PIP (n = 164), a piperacillin Co >20.95 mg/L had a sensitivity of 78% and specificity of 43% to identify patients with liver injury. In a multivariate analysis, piperacillin Co >20.95 mg was independently associated with the development of liver injury.
Conclusions:
In this cohort of patients, no clear association was found between trough concentration of β-lactams and the development of liver injury. The potential hepatotoxicity of piperacillin warrants further investigation.