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

Abstract

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.

Evaluation of the safety of piperacillin‐tazobactam extended infusion in pediatric cystic fibrosis patients

“…Similar to our study with PZT, they found no difference in adverse drug events between TI and EI cefepime. The incidence of AKI between the two groups was also similar to ours, with 16 (11.8%) in the EI group compared with 6 (11.3%) in the TI group ( p = 0.92) 26 . In their single‐center, retrospective matched‐cohort study of over 2000 adult patients, Cotner et al 27 found no statistical difference in the rate of AKI between TI and EI beta‐lactams (18.6% vs. 21.6%, p = 0.1, respectively).…”

“…The incidence of AKI between the two groups was also similar to ours, with 16 (11.8%) in the EI group compared with 6 (11.3%) in the TI group (p = 0.92). 26 In their single-center, retrospective matched-cohort study of over 2000 adult patients,…”

Clinical recommendations for the inpatient management of lower respiratory tract infections in children and adolescents with severe neurological impairment in Germany

“…These considerations lead to the rationale for expanding the spectrum of activity by either switching from aminopenicillin plus beta-lactamase inhibitor to the broader gram-negative active piperacillin-tazobactam or further expanding the gram-negative spectrum of the existing piperacillin-tazobactam therapy. In this context, there is favorable evidence from CF therapy for the combination therapy of a beta-lactam antibiotic or a Pseudomonas -active cephalosporin [ 65 , 66 ] with tobramycin [ 67 , 68 ] or fosfomycin [ 69 – 71 ]. Extended infusion of beta-lactam antibiotics has been shown to be effective and, depending on the clinical situation, is an option to increase the efficacy of ABT [ 72 ].…”