cefiderocol
Sources réglementaires consultées
Indications approuvées
- Infections dues à des germes aérobies à Gram négatif chez l’adulte avec des options thérapeutiques limitées.
Contre-indications
Absolues
- Hypersensibilité au céfidérocol ou antécédent de réaction immédiate sévère à une autre bêta-lactamine.
Mises en garde cliniques
- Mise en garde majeure · Une hypersensibilité sévère ou une anaphylaxie peut survenir ; rechercher les antécédents d’allergie aux bêta-lactamines et arrêter en cas de réaction allergique. — CIMA/AEMPS, ficha técnica 1201434
- Mise en garde majeure · Une diarrhée et une colite à Clostridioides difficile peuvent survenir pendant ou après le traitement ; évaluer toute diarrhée importante. — CIMA/AEMPS, ficha técnica 1201434
- Mise en garde majeure · L’accumulation, notamment en cas d’insuffisance rénale ou de dose non ajustée, peut provoquer encéphalopathie, myoclonies ou convulsions ; adapter à la fonction rénale et surveiller l’état neurologique. — CIMA/AEMPS, ficha técnica 1201434
- Un essai dans des infections à Gram négatif résistantes a montré une mortalité supérieure à celle du comparateur, principalement dans la pneumonie, la bactériémie ou le sepsis ; réserver le traitement aux infections avec peu d’options et confirmer la sensibilité si possible. — CIMA/AEMPS, ficha técnica 1201434
Effets indésirables
Communs (≥1%)
Nausées, diarrhée et éruption cutanée
Rares mais graves
Anaphylaxie, colite à C. difficile et cytopénies sévères
Grossesse et allaitement
Pendant la grossesse, utiliser uniquement en cas d’indication clinique. Évaluer l’allaitement selon l’exposition dans le lait et l’état du nourrisson décrits dans le résumé des caractéristiques du produit.
Bibliographie récente (PubMed)
Carbapenem-resistant Acinetobacter baumannii has been associated with over three hundred thousand annual deaths globally. It is resistant to most available antibiotics and associated with high morbidity and mortality. No global consensus currently exists for treatment strategies that balance safety and efficacy because of heterogeneity of treatment regimens in current clinical practice and scarcity of large-scale controlled studies arising from difficulties in establishing robust clinical outcomes. This review outlines the epidemiology and resistance mechanisms of carbapenem-resistant A. baumannii, then summarizes available clinical data on each approved agent with activity against this pathogen. Emerging treatment options such as cefiderocol and sulbactam-durlobactam show promise, but their success hinges on comprehensive clinical validation and access in regions most impacted by this pathogen. New therapeutic modalities that are in various stages of clinical development are also discussed.
Patients with severe carbapenem-resistant Acinetobacter baumannii (CRAB) infections currently face significant treatment challenges. When patients display signs of infection and the clinical suspicion of CRAB infections is high, appropriate treatment should be immediately provided. However, current treatment plans and clinical data for CRAB are limited. Inherent and acquired resistance mechanisms, as well as host factors, significantly restrict options for empirical medication. Moreover, inappropriate drug coverage can have detrimental effects on patients. Most existing studies have limitations, such as a restricted sample size, and are predominantly observational or non-randomized, which report significant variability in patient infection severity and comorbidities. Therefore, a gold-standard therapy remains lacking. Current and future treatment options of infections due to CRAB were described in this review. The dose and considerable side effects restrict treatment options for polymyxins, and high doses of ampicillin-sulbactam or tigecycline appear to be the best option at the time of initial treatment. Moreover, new drugs such as durlobactam and cefiderocol have substantial therapeutic capabilities and may be effective salvage treatments. Bacteriophages and antimicrobial peptides may serve as alternative treatment options in the near future. The advantages of a combination antimicrobial regimen appear to predominate those of a single regimen. Despite its significant nephrotoxicity, colistin is considered a primary treatment and is often used in combination with antimicrobials, such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin. The Infectious Diseases Society of America (IDSA) has deemed high-dose ampicillin-sulbactam, which is typically combined with high-dose tigecycline, polymyxin, and other antibacterial agents, the best option for treating serious CRAB infections. A rational combination of drug use and the exploration of new therapeutic drug
Antibacterial drug resistance of gram-negative bacteria (GNB) results in high morbidity and mortality of GNB infection, seriously threaten human health globally. Developing new antibiotics has become the critical need for dealing with drug-resistant bacterial infections. Cefiderocol is an iron carrier cephalosporin that achieves drug accumulation through a unique "Trojan horse" strategy into the bacterial periplasm. It shows high antibacterial activity against multidrug-resistant (MDR) Enterobacteriaceae and MDR non-fermentative bacteria. The application of cefiderocol offers new hope for treating clinical drug-resistant bacterial infections. However, limited clinical data and uncertainties about its resistance mechanisms constrain the choice of its therapeutic use. This review aimed to summarize the clinical applications, drug resistance mechanisms, and co-administration of cefiderocol.
The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children. A panel of 13 pediatric infectious diseases specialists, including 11 pharmacists and 2 physicians, reviewed existing pharmacokinetic/pharmacodynamic, animal, and clinical data for newer β-lactam agents that are available in the United States and suggested for the treatment of AMR infections (ie, cefiderocol, ceftazidime-avibactam, ceftazidime-avibactam and aztreonam, ceftolozane-tazobactam, imipenem-cilastatin-relebactam, meropenem-vaborbactam, sulbactam-durlobactam). Suggested dosing for ampicillin-sulbactam is also provided, given complexities in dosing for carbapenem-resistant Acinetobacter baumannii infections. Consensus-based suggested dosing for β-lactam agents used to treat AMR infections in neonates, infants, children, and adolescents and relevant supporting evidence are provided. Content is up to date as of December 1, 2024. Gaps and limitations to existing data are discussed. Optimizing antibiotic dosing is critical to improving the outcomes of children with AMR infections.
Pneumonia is frequently encountered in clinical practice, and Gram-negative bacilli constitute a significant proportion of its aetiology, especially when it is acquired in a hospital setting. With the alarming global rise in multidrug resistance in Gram-negative bacilli, antibiotic therapy for treating patients with pneumonia is challenging and must be guided by in vitro susceptibility results. In this review, we provide an overview of antibiotics newly approved for the treatment of pneumonia caused by Gram-negative bacilli. Ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam have potent activity against some of the carbapenem-resistant Enterobacterales, especially Klebsiella pneumoniae carbapenemase producers. Several novel antibiotics have potent activity against multidrug-resistant Pseudomonas aeruginosa, such as ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relabactam and cefiderocol. Cefiderocol may also play an important role in the management of pneumonia caused by Acinetobacter baumannii, along with plazomicin and eravacycline.