cefiderocol
Regulatory sources consulted
Approved indications
- Infections due to aerobic gram-negative organisms in adults with limited treatment options.
Contraindications
Absolute
- Hypersensitivity to cefiderocol or a history of a severe immediate reaction to another beta-lactam.
Clinical warnings
- Major warning · Severe hypersensitivity or anaphylaxis may occur; review beta-lactam allergy history and discontinue if an allergic reaction develops. — CIMA/AEMPS, ficha técnica 1201434
- Major warning · Clostridioides difficile-associated diarrhea and colitis may occur during or after treatment; assess significant diarrhea. — CIMA/AEMPS, ficha técnica 1201434
- Major warning · Accumulation, especially with renal impairment or unadjusted doses, may cause encephalopathy, myoclonus, or seizures; adjust for renal function and monitor neurologic status. — CIMA/AEMPS, ficha técnica 1201434
- A trial in resistant gram-negative infections found higher mortality than with comparator therapy, mainly in pneumonia, bloodstream infection, or sepsis; reserve treatment for infections with limited options and confirm susceptibility when possible. — CIMA/AEMPS, ficha técnica 1201434
Adverse events
Common (≥1%)
Nausea, diarrhea, and rash
Rare but serious
Anaphylaxis, C. difficile colitis, and severe cytopenias
Pregnancy and lactation
During pregnancy, use only when clinically indicated. Assess breastfeeding according to milk exposure and the infant’s condition described in the product information.
Recent literature (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.