Effect of Cefepime on Neurotoxicity Development in Critically Ill Adults with Renal Dysfunction.
Pharmacodynamic and pathophysiologic changes in critically ill adults receiving cefepime may increase the risk of adverse events. This study evaluated the impact of cefepime exposure on neurotoxicity development in critically ill adults with renal dysfunction.Critically ill adults with creatinine clearance <60 mL/min who received cefepime for ≥48 hours between 1 January 2014 and 31 July 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’s 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 ± 1.6 g vs. 7.7 ± 2.2 g, p<0.001). Cefepime-associated neurotoxicity occurred infrequently in both lower- (n=108) and higher-dose (n=92) cefepime groups (4% vs. 10%, odds ratio (OR) 2.82, 95% confidence interval (CI) 0.84-9.48, p=0.093). 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=0.72) and numerically greater in the higher-dose cefepime group in the severe renal dysfunction subgroup (0 vs. 16%, p=0.064). 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 though this requires additional investigation.