Evaluation of the safety of cefepime prolonged infusions in pediatric patients with cystic fibrosis.

OBJECTIVE

Pediatric cystic fibrosis (CF) patients possess unique pharmacokinetics and may benefit from prolonged beta-lactam infusions to optimize pharmacodynamics. This study compared adverse drug event (ADE) rates with cefepime prolonged (PI) and standard infusions (SI).

METHODS

This retrospective study included pediatric patients treated with cefepime for CF exacerbations between 2009 and 2019. One encounter per patient was analyzed with prioritization of SI encounters given sample size limitations. Baseline lab abnormalities, seizure disorders, and bleeding were exclusion criteria. The primary outcome was a composite safety endpoint (acute kidney injury [AKI], hepatotoxicity, hematologic toxicity, neurotoxicity, and hypersensitivity).

RESULTS

Of 188 patients, 135 received PI and 53 received SI. Baseline characteristics were similar between groups. More PI patients used CF transmembrane conductance regulator (CFTR) modulators (25% vs. 0%, p < 0.01) or had antibiotic allergies (62% vs. 38%, p = 0.02). Difference in rates of composite safety endpoint was not statistically significant between PI and SI (21 [15.6%] vs. 6 [11.3%] p = 0.46) nor was incidence of AKI (16 [11.8%] vs. 6 [11.3%], p = 0.92). Other ADEs were rarely observed. Length of stay (12.2 vs. 10.1 days, p = 0.06), change in discharge ppFEV1 from admission (13 vs. 12, p = 0.91) or from baseline (-4 vs. -6.5, p = 0.33), and time to next exacerbation (249.7 vs. 192.5 days, p = 0.93) were similar.

CONCLUSIONS

No difference in risk of ADEs including AKI was seen with cefepime PI in pediatric CF patients. Clinical outcomes were not significantly different between groups, but sample size may have limited comparison. PI cefepime may be considered in pediatric CF patients to optimize pharmacodynamics.