Vol.73 No.S-1 April 2025
Use of cefiderocol in pediatric patients and specific populations―Based on case reports―
1)Department of Infectious Diseases, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, Japan
2)Department of Infection Prevention and Control, Hyogo Medical University Hospital
3)Disease Control and Prevention Center, National Center for Global Health and Medicine Hospital
4)Division of Infection Control and Prevention, Department of Medical Safety Management, Kindai University Hospital
Abstract
Cefiderocol (CFDC), a novel antimicrobial agent that utilizes the active iron transport system of bacteria for cell entry, has been demonstrated in the phase II and phase III trials to be safe and effective in patients with infections caused by Gram-negative bacteria, including bacteria resistant to existing antimicrobial agents. This review focuses on case reports of infections that not included in these trials and the use of CFDC in pediatric patients and special patient populations.
The PEDI-CEFI study confirmed favorable tolerability of CFDC in pediatric inpatients, and the dose necessary to achieve an area under the concentration-time curve equivalent to that observed in adults was identified as 60 mg/kg per dose for patients with a body weight of less than 34 kg and 2 g per dose for patients with a body weight of 34 kg or over. The drug (both doses) was administered by intravenous infusion over 3 hours at intervals of 8 hours.
Despite initial concerns that an extracorporeal membrane oxygenator might affect the pharmacokinetics of CFDC, it has been confirmed that CFDC is not adsorbed onto the circuit and that it can be applied at the approved dosages inpatients receiving extracorporeal membrane oxygenation. On the other hand, inpatients undergoing continuous hemodiafiltration, dosage adjustments are necessary due to the variability in clearance based on the patient's residual renal function and blood flow rates, which may lead to a decrease in exposure to CFDC.
CFDC has been shown to be effective for central nervous system infections, with proven penetration into the cerebrospinal fluid. For ocular infections, meropenem is the only antibacterial agent that has been shown until date to have the ability to penetrate the vitreous body and exert sufficient clinical efficacy, so that other options were needed. However, there is currently insufficient data in regard to the ability of CFDC to penetrate the vitreous body or the possibility of administration of CFDC in the form of eye drops. For skin and soft tissue infections, CFDC has been reported to have the ability to penetrate the skin and muscles, suggesting that it could be a useful treatment option for skin and soft tissue infections. Furthermore, there are case reports of the efficacy of CFDC in immunocompromised patients with infections caused by multidrug-resistant bacteria. However, there is still no consensus on whether CFDC should be used alone or in combination with other antibiotics, or on what the most suitable combination regimen might be.
CFDC is indicated for infections caused by carbapenem-resistant bacteria, and evidence accumulated from studies in pediatric populations and case reports presented here suggests that CFDC may be a useful treatment agent in the following specific populations not included in the phase II and phase III trials.
Key word
cefiderocol, Gram-negative bacteria, antimicrobial resistance, child dose, dialysis
Received
January 29, 2025
Accepted
February 18, 2025
Jpn. J. Chemother. 73 (S-1): 62-73, 2025
