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

Abstract

Pharmacodynamic and pathophysiologic changes in critically ill adults receiving cefepime may increase the risk of adverse events. What is the impact of cefepime exposure on neurotoxicity development in critically ill adults with renal dysfunction? Critically ill adults with creatinine clearance< 60mL/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 (≥ 8g vs< 8g in first 48 hours) or severe (≥ 4g vs< 4g 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. Cefepime total dose in the first 48 hours was greater in the higher-dose cefepime group (3.7 ± 1.6g vs7.7 ± 2.2 g; P< .001). Cefepime-associated neurotoxicity occurred infrequently in both lower- (n= 108) and higher-dose (n= 92) cefepime groups (4%vs10%, 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%vs7%, 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 vs16%, 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%). 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.