Cefiderocol safe to use in hospitalized children with bacterial infection

A 3-hour infusion of cefiderocol in hospitalized paediatric patients is well tolerated and demonstrates activity against clinically relevant Gram-negative species of bacterial infections, reports a phase II study.

“Multiple-dose cefiderocol, administered for 5–14 days and according to body weight, achieved steady-state plasma concentrations that remained above the susceptibility breakpoints of Gram-negative bacteria throughout the dosing period,” the investigators said.

The pharmacokinetics, safety, and tolerability of single- and multiple-dose cefiderocol (as a 3-hour infusion, every 8 hours, dosed at 2,000 mg for body weight ≥34 kg and at 60 mg/kg for body weight <34 kg) were examined in this multicentre, open-label phase II study. Fifty-three paediatric patients with aerobic Gram-negative bacterial infection (median age 73.5. months) were included.

Patients who received multiple-dose cefiderocol required standard-of-care systemic antibiotics for 5–14 days. Participants were then categorized into four cohorts (cohort 1: 12 to <18 years; cohort 2: 6 to <12 years; cohort 3: 2 to <6 years; cohort 4: 3 months to <2 years).

Plasma concentration profiles did not differ significantly with single-dose (n=24) and multiple-dose (n=29) cefiderocol, regardless of age and body weight in those with normal renal function or mild renal impairment. [Pediatr Infec Dis J 2025;44:136-142]

At the end of infusion, the geometric mean concentration ranged between 72.7 and 97.1 μg/mL for single-dose cefiderocol and between 88.8 and 106.0 μg/mL for multiple doses. The corresponding trough concentrations at 8 hours ranged from 7.86 to 10.8 μg/mL with the single dose and from 9.64 to 18.1 μg/mL for multiple doses.

No deaths occurred, and no cefiderocol-related serious adverse events (AEs) were reported. There were also no significant related laboratory abnormalities or discontinuations.

“Cefiderocol was well tolerated in both the single-dose and multiple-dose phases of the study, with infrequent AEs, none of which were related to cefiderocol,” the investigators said. “Thus, cefiderocol could be a valuable treatment option for paediatric patients with multidrug-resistant and carbapenem-resistant Gram-negative bacterial infections.”

Adult studies

In previous studies involving adult patients, cefiderocol exhibited effective lung epithelial lining fluid penetration in parallel with plasma concentrations after a single intravenous dose (2,000 mg) in healthy participants. [Antimicrob Agents Chemother 2017;61:e00700-17]

Additionally, cefiderocol achieved enough lung epithelial lining fluid concentrations to treat Gram-negative pulmonary bacterial infections with a minimum inhibitory concentration (MIC) of ≤4 µg/mL in patients with pneumonia on mechanical ventilation and receiving multiple doses (2 g every 8 hours). [J Antimicrob Chemother 2021;76:2902-2905]

“The pharmacodynamic driver of cefiderocol efficacy is the proportion of the dosing interval spent above the MIC by the unbound antibiotic at the site of infection,” the investigators noted. [Antimicrob Agents Chemother 2017;61:e01022-17]

Cefiderocol, a siderophore-conjugated cephalosporin, works against several aerobic Gram-negative pathogens, including multidrug-resistant organisms. [Infect Dis Ther 2023;12:777-806; Expert Rev Anti Infect Ther 2022;20:1077-1094; Microbiol Spectr 2022;10:e0271221]

Cefiderocol is approved in Europe for the treatment of adults with Gram-negative bacterial infections and in the US for adults with complicated urinary tract infection and pneumonia. However, it is not yet approved for use in children, according to the investigators.