A recent 2025 review compiled panel recommendations for suggested dosing of beta-lactam antibiotics for treatment of antimicrobial-resistant gram negative infections in children. These pediatric dosing regimens are primarily based on a recent pharmacokinetic study conducted in children from birth to age <18 years (Table 1). The dosing utilized in this study is predicted to achieve over 90% PTA for 75% fT > MIC for organisms with MICs of up to 4 µg/mL. Clinical data demonstrating the use of cefiderocol in children is limited to case reports and case series, which generally utilized a dose of 60 mg/kg Q8 hours (maximum dose 2 g). One case report used a 40 mg/kg dose Q8 hours in a 5-week-old infant. Ultimately, panel recommendations based on the limited data also reiterate the 60 mg/kg dose (maximum dose 2 g) given IV Q8 hours, with infusions over 3 hours in children ≥ 3 months to <18 years of age. Cefiderocol is considered a reasonable option for treatment of gram-negative central nervous system infections caused by antimicrobial-resistant pathogens; based on the current data, the same dose may be used for CNS and non-CNS infections in children. Dosing at 6 hour intervals for CNS infections should be determined on a case-by-case basis in children due to lack of data. Full dosing recommendations are listed in Table 2. [1]
While novel beta-lactam antibiotics, such as cefiderocol, show promise for treating multidrug-resistant gram-negative infections in pediatric settings, clinical data are predominantly derived from small studies and/or case reports. Two recent trials, one published and one ongoing, are investigating cefiderocol in hospitalized pediatric patients, utilizing proposed doses of 60 mg/kg every 8 hours for those weighing <34 kg and 2 g every 8 hours for those weighing ≥ 34 kg, administered via a 3-hour extended infusion regimen. Notably, the primary endpoints of these trials focus on safety and pharmacokinetic measures, not clinical efficacy. To prevent the proliferation of drug resistance, the use of cefiderocol should be reserved for infections caused by metallo-β-lactamase-producing Enterobacterales, multidrug-resistant (MDR) Pseudomonas aeruginosa, and other MDR gram-negative bacteria deemed non-susceptible to alternative therapies. [2], [3], [4], [5]
A 2024 single-center, prospective, observational study evaluated cefiderocol susceptibility among multidrug-resistant Gram-negative bacteria (MDR-GNB) isolated from pediatric patients at a tertiary care children’s hospital. All phenotypically carbapenem-resistant or genotypically carbapenemase-producing Gram-negative isolates detected between January 2020 and June 2023 were included and assessed for cefiderocol susceptibility using disk diffusion in accordance with EUCAST criteria. Carbapenem resistance was identified through minimal inhibitory concentration (MIC) thresholds for meropenem (≥0.125 mg/L), followed by molecular detection of carbapenemase genes (bla-KPC, bla-NDM, bla-VIM, bla-OXA-48). The analysis stratified isolates into Enterobacterales and non-fermenting Gram-negative bacteria (NF-GNB), with comparative assessment based on cefiderocol susceptibility profiles and correlated antimicrobial resistance data. Among 47 Gram-negative isolates from 36 pediatric patients, 38% exhibited cefiderocol resistance. Enterobacterales showed a markedly higher resistance rate (53%, 16/30 isolates) compared to NF-GNB (12%, 2/17 isolates). All cefiderocol-resistant Enterobacterales were carbapenemase producers, with metallo-β-lactamase (MBL) expression—specifically NDM and VIM—demonstrated in 69% of resistant isolates compared to 36% of susceptible strains. Resistance to ceftazidime-avibactam was also more prevalent among cefiderocol-resistant Enterobacterales (62% vs. 36%), underscoring a potential cross-resistance mechanism. Notably, none of the patients had prior exposure to cefiderocol, suggesting de novo resistance or horizontal transmission. Prior hospitalization and broader antimicrobial exposure were more frequent in patients from whom resistant strains were isolated. Among NF-GNB, resistance mechanisms were not fully elucidated, though the low prevalence of carbapenemases in this group suggests alternate pathways such as efflux or porin modifications. Despite high resistance prevalence, no significant differences in ICU admission, infection development, or short-term mortality were observed between groups. These findings highlight the importance of cautious cefiderocol use, especially in empirical and monotherapy regimens, in pediatric settings experiencing high baseline rates of resistance. Yet, as the study was conducted in Italy, the results may not accurately reflect the U.S. resistance patterns. [6]
In addition to several case reports (see Tables 3-6), some small retrospective case series also demonstrate use of cefiderocol in pediatric settings. A 2024 single-center, retrospective case series evaluated the real-world use of cefiderocol in pediatric inpatients with infections or colonization due to multidrug-resistant Gram-negative bacteria (MDR-GNB). Pediatric patients aged 0.6 to 15.8 years who received cefiderocol were included. Cefiderocol was administered for 18 episodes in 14 children, with 10 episodes representing serious or invasive MDR-GNB infections and 8 episodes involving prophylactic or empiric use due to known colonization. Pathogens targeted included Stenotrophomonas maltophilia (6/10), Acinetobacter baumannii, Pseudomonas aeruginosa, Pseudomonas putida, and Klebsiella pneumoniae. Antimicrobial susceptibility was determined using EUCAST disk diffusion methodology, and cefiderocol was prescribed based on interdisciplinary antimicrobial stewardship input. Dosing followed pediatric protocols extrapolated from pharmacokinetic modeling, with 60 mg/kg q8h dosing (maximum 2 g) infused over 3 hours. Among children treated for invasive infection, favorable clinical response, defined by symptom improvement and biochemical markers, was achieved in 6 of 10 episodes. The 30-day mortality rate was 10% in this cohort and 12.5% overall, with both deaths primarily attributed to progression of underlying disease rather than infection. One episode of microbiological failure and one recurrence of infection were documented. Notably, persistent colonization after cefiderocol cessation was observed in 72% of evaluable patients, though re-sampling intervals were inconsistent. Adverse effects were generally mild, with two cases of desquamating rash, one later attributed to graft-versus-host disease. Mild transaminitis and purple urine were each reported once without requiring discontinuation. All patients received combination antimicrobial therapy, and in three cases cefiderocol was the only active agent based on susceptibility testing. Clinical outcomes compared favorably to previously reported adult case series. These findings underscore the potential utility and tolerability of cefiderocol in pediatric patients with limited therapeutic alternatives for MDR-GNB infections. [7]
Additionally, a 2021 multicenter, retrospective case series published in Clinical Infectious Diseases evaluated the clinical utility of cefiderocol in eight cystic fibrosis (CF) patients with extensively drug-resistant Achromobacter xylosoxidans infections. Data were collected through the United States cefiderocol compassionate use program, identifying patients from four participating institutions. All subjects had respiratory tract infections, with complications in some cases including bacteremia and empyema. A total of twelve cefiderocol treatment courses were administered across the cohort, with four patients receiving multiple courses. Drug dosing was aligned with manufacturer guidance and tailored to renal function, with adults receiving 2 g IV every 8 hours and pediatric patients receiving 60 mg/kg every 8 hours. In eleven of twelve treatment episodes, cefiderocol was administered in combination with other anti-gram-negative agents. Susceptibility testing of pretreatment isolates, based on Pseudomonas aeruginosa breakpoints, revealed in vitro cefiderocol resistance in three of eight patients prior to therapy initiation. Clinical response, defined as symptom resolution or improvement, was achieved in eleven of twelve cefiderocol courses, indicating promising clinical outcomes despite baseline resistance in some cases. Notably, microbiologic relapse occurred following eleven of twelve regimens, though resistance emergence post-treatment was not observed. In five instances where pretreatment isolates were susceptible, posttreatment isolates remained susceptible, suggesting a lack of selection for resistance during cefiderocol exposure. One pediatric patient who also received adjunctive bacteriophage therapy did not experience microbial relapse. Among the six patients who underwent lung transplantation, cefiderocol was employed perioperatively, often as part of a broader empiric regimen, and contributed to posttransplant infection management without observed drug–drug interactions or severe toxicity. Adverse effects were infrequent and included mild peripheral neuropathy and an unexplained chylothorax. These findings highlight both the potential efficacy of cefiderocol in treating multidrug-resistant A. xylosoxidans in CF patients and the challenges of sustained microbiologic eradication in this population. [8]