Ertapenem blood concentration: A retrospective cohort study to analyse risk of neurotoxicity

Br J Clin Pharmacol. 2023 Sep;89(9):2843-2850. doi: 10.1111/bcp.15782. Epub 2023 May 26.

Abstract

Aims: Several cases of ertapenem-related neurotoxicity have been published in the current literature. However, studies evaluating the ertapenem blood concentration (EBC) as a risk of these adverse events are scarce. We aimed to evaluate the relationship between the trough EBC and the risk of neurological toxicity.

Methods: This was a retrospective study, including patients who underwent ertapenem treatment between October 2019 and February 2021. We excluded patients in the critical care unit and those whose blood samples were not properly taken in order to analyse ertapenem trough concentration. We also excluded patients whose clinical follow-up was not properly realized for the entire period of ertapenem treatment. The main outcome was the presence of any suspicious neurological side effect owing to ertapenem administration and its relationship with the plasma concentration. Secondary outcomes were to identify clinical and analytical data contributing to a higher risk of neurotoxicity.

Results: The initial cohort comprised 158 individuals. For the final analysis we evaluated 102 patients, reporting a neurological alteration in 13/102 (12.7%). Mean trough EBC was significantly higher in patients showing neurotoxicity in comparison with those who did not (37.8 mcg mL-1 , standard deviation [SD] ± 35.7 vs. 14.6 mcg mL-1 , SD ± 15.2; P = .002). In multivariable logistic regression analysis, EBC (odds ratio [OR] = 1.07; P = .006), a moderate renal insufficiency (OR = 9.2; P = .02) and a history of previous neurologic disease (OR = 9.9; P = .02) were identified as risk factors of neurological alteration during ertapenem treatment.

Conclusions: In patients at risk, determining the ertapenem plasma concentration may help to minimize the risk of neurotoxicity.

Keywords: ertapenem; neurotoxicity; plasma trough concentration; therapeutic drug monitoring.

MeSH terms

  • Anti-Bacterial Agents* / adverse effects
  • Ertapenem / adverse effects
  • Humans
  • Neurotoxicity Syndromes* / drug therapy
  • Neurotoxicity Syndromes* / epidemiology
  • Neurotoxicity Syndromes* / etiology
  • Retrospective Studies
  • Risk Factors

Substances

  • Ertapenem
  • Anti-Bacterial Agents