Effect of Cefepime on Neurotoxicity Development in Critically Ill Adults With Renal Dysfunction

Abstract

Background: Pharmacodynamic and pathophysiologic changes in critically ill adults receiving cefepime may increase the risk of adverse events.

Research question: What is the impact of cefepime exposure on neurotoxicity development in critically ill adults with renal dysfunction?

Study design and methods: Critically ill adults with creatinine clearance < 60 mL/min who received cefepime for ≥ 48 hours between January 1, 2014 and July 31, 2018 were evaluated for cefepime-associated neurotoxicity (CAN) development. Higher- and lower-dose cefepime exposure groups stratified by moderate (≥ 8 g vs < 8 g in first 48 hours) or severe (≥ 4 g vs < 4 g in first 48 hours) renal dysfunction were compared. Between-group comparisons were performed using Fisher exact tests. CAN-free survival was evaluated using Kaplan-Meier curves and log-rank tests.

Results: Cefepime total dose in the first 48 hours was greater in the higher-dose cefepime group (3.7 ± 1.6 g vs 7.7 ± 2.2 g; P < .001). Cefepime-associated neurotoxicity occurred infrequently in both lower- (n = 108) and higher-dose (n = 92) cefepime groups (4% vs 10%, OR 2.82, 95% CI, 0.84-9.48, P = .093). The frequencies of cefepime-associated neurotoxicity were similar between lower- and higher-dose cefepime groups when moderate renal dysfunction subgroups were compared (5% vs 7%, OR 1.42, 95% CI, 0.34-5.92, P = .72) and numerically greater in the higher-dose cefepime group in the severe renal dysfunction subgroup (0 vs 16%, P = .064). Times to cefepime-associated neurotoxicity development and resolution were similar between lower- and higher-dose groups. Durations of CAN-free survival were similar between lower- and higher-dose groups. Most patients who developed cefepime-associated neurotoxicity displayed altered mental status (n = 12, 92%).

Interpretation: Cefepime-associated neurotoxicity is an uncommon occurrence in critically ill adults. Patients with severe renal dysfunction receiving higher-dose cefepime may be at greater risk of cefepime-associated neurotoxicity, although this requires additional investigation.

Keywords: cefepime; critically ill; neurotoxicity; renal dysfunction.