Efficacy and safety of ertapenem dosing in patients with ESBL producing Enterobacterales infections utilizing renal replacement therapies

Abstract

Purpose: The clinical efficacy and safety of ertapenem use in patients undergoing renal replacement therapies (RRT) are not well-documented. Therefore, we aimed to investigate the safety and efficacy of ertapenem in patients with sepsis secondary to Enterobacterales who are undergoing RRT. Methods: A retrospective cohort study was conducted on patients who met the inclusion criteria at our hospital between May 2015 and December 2021. The primary endpoint was 30-day mortality. Secondary endpoints included clinical cure, microbiologic cure, recurrence rate, and incidence of seizures. Results: During the study period, 158 patients met the inclusion criteria. Of these, 86 were male (54.4%), the mean age was 66.4 ± 13.8 years, and the mean weight was 77 ± 22.4 kg. The most common diagnosis was bacteremia in 48 (30.4%) subjects, followed by urinary tract infection in 39 (24.7%) subjects, and pneumonia in 35 (22.2%) patients. The most isolated pathogens were Escherichia coli, followed by Klebsiella species. The median ertapenem dose was 0.5 g intravenously (IV) daily in those who received intermittent hemodialysis (IHD) and 1 g IV daily for those who received continuous veno-venous hemofiltration (CVVH). The 30-day mortality rate was 24%, the clinical cure rate was 89.2%, the microbiologic cure rate was 82%, the 30-day recurrence rate was 41.1%, and the incidence of seizures was 2.5%. Multivariate logistic regression analysis indicated that age (OR 1.04 [95% CI: 1.003–1.075]), being critically ill at therapy initiation (OR 2.9 [95% CI: 1.1–7.5]), and Enterobacterales other than Klebsiella species and Escherichia coli (OR 3.8 [95% CI: 1.1–12.5]) were significant independent risk factors associated with mortality in this population. Ertapenem dose was not associated with mortality. Conclusion: Our findings suggest that the commonly used doses of ertapenem in patients undergoing IHD and CVVH are clinically effective but may pose a higher risk of seizures. A comprehensive pharmacokinetic study is needed to determine the most effective and safe dose for this population.