Fetroja (Cefiderocol) for Complicated Infections: Usage and Dosing Guidelines
Fetroja (cefiderocol) is indicated for treating complicated infections in adults with limited treatment options, with the standard dose being 2 grams administered intravenously every 8 hours over 3 hours, with dose adjustments required for renal impairment. 1
Approved Indications
Fetroja is FDA-approved for adults (18 years or older) with:
- Complicated urinary tract infections (cUTI), including pyelonephritis
- Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) 1
Mechanism of Action and Spectrum
Fetroja is a novel siderophore cephalosporin with a unique mechanism of action:
- Uses bacterial iron transport channels to penetrate the periplasmic space of gram-negative bacteria
- Binds to penicillin-binding proteins to inhibit cell wall synthesis
- Has enhanced stability against various β-lactamases, including carbapenemases 2
Fetroja is active against difficult-to-treat gram-negative pathogens, including:
- Carbapenem-resistant Enterobacterales (CRE)
- Carbapenem-resistant Pseudomonas aeruginosa (CRPA)
- Acinetobacter baumannii complex
- Stenotrophomonas maltophilia 3, 1
Standard Dosing Regimen
The recommended dosage of Fetroja is:
- 2 grams administered intravenously every 8 hours
- Infused over 3 hours
- Treatment duration: 7-14 days, depending on infection site and severity 1, 4
Renal Dose Adjustments
Dose adjustment is required based on creatinine clearance (CrCL):
- CrCL 60-119 mL/min: Standard dose (2g q8h)
- CrCL <60 mL/min or ≥120 mL/min: Dose adjustment required 5
Clinical Evidence
In a phase 2 randomized clinical trial for complicated UTIs:
- Fetroja demonstrated superior composite clinical and microbiological response rates (72.6%) compared to imipenem-cilastatin (54.6%)
- Clinical cure rates were similar between Fetroja (89.7%) and imipenem-cilastatin (87.4%)
- Microbiological eradication rates were higher with Fetroja (73.0%) compared to imipenem-cilastatin (56.3%) 1, 6
Role in Treatment of Multidrug-Resistant Infections
According to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines:
- For patients with severe infections due to carbapenem-resistant Enterobacterales (CRE) carrying metallo-β-lactamases and/or resistant to other antibiotics, Fetroja is conditionally recommended
- Fetroja is particularly valuable for infections caused by organisms resistant to ceftazidime-avibactam and meropenem-vaborbactam 3
Safety Profile
Fetroja is generally well-tolerated:
- Most common adverse events are gastrointestinal symptoms (diarrhea, constipation, nausea)
- Safety profile comparable to other cephalosporin antibiotics 2, 4
Important Clinical Considerations
- Fetroja should only be used for infections proven or strongly suspected to be caused by susceptible bacteria to reduce the development of drug-resistant bacteria 1
- Pharmacokinetic/pharmacodynamic studies show that the standard dosing regimen achieves adequate plasma exposure in most patients, including those with augmented renal function 5
- For severe infections caused by multidrug-resistant pathogens, Fetroja may be used as monotherapy when susceptible in vitro 3
Antimicrobial Stewardship Considerations
- Reserve Fetroja for patients with limited treatment options due to resistance
- Obtain appropriate cultures before initiating therapy
- Consider local antibiogram patterns when selecting therapy
- Monitor for clinical and microbiological response
Fetroja represents an important addition to the antimicrobial armamentarium for treating complicated infections caused by multidrug-resistant gram-negative pathogens, particularly when other options are limited due to resistance or contraindications.