Version July 2025
Note: Not recommended for routine empiric use. Reserve for patients with or at risk for certain extensively drug-resistant gram-negative pathogens (nonsusceptible to ≥1 agent in all but 2 or fewer antimicrobial classes) (eg, carbapenem-resistant Acinetobacter baumannii or Enterobacterales, P. aeruginosa with difficult-to-treat resistance, Stenotrophomonas maltophilia) (Ref).
Pneumonia, hospital acquired or ventilator associated (alternative agent):
Note: Reserve for when preferred extended-spectrum agents cannot be used (Ref).
IV: 2 g every 8 hours (Ref). Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (Ref). Note: For patients with CrCl ≥120 mL/minute, increase dose to 2 g every 6 hours (Ref).
Urinary tract infection:
Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection) (off-label use): Note: Reserve for patients with difficult-to-treat P. aeruginosa or carbapenem-resistant Enterobacterales.
IV: 2 g every 8 hours (Ref).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms):
IV: 2 g every 8 hours. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days; for patients with symptomatic improvement within the first 48 to 72 hours of therapy, some experts recommend shorter courses of 5 to 10 days (or 7 to 10 days if therapy is completed with cefiderocol) (Ref). Note: For patients with CrCl ≥120 mL/minute, increase dose to 2 g every 6 hours.
Altered kidney function:
IV: Note: Kidney function may be estimated using the Cockcroft-Gault formula.
CrCl ≥120 mL/minute: 2 g every 6 hours.
CrCl 60 to <120 mL/minute: 2 g every 8 hours.
CrCl 30 to <60 mL/minute: 1.5 g every 8 hours.
CrCl 15 to <30 mL/minute: 1 g every 8 hours.
CrCl <15 mL/minute: 750 mg every 12 hours.
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: 2 g every 6 hours.
Hemodialysis, intermittent (three times weekly): IV: Dialyzable (~60% in a 3- to 4-hour hemodialysis session): 750 mg every 12 hours; dose should be given immediately after hemodialysis on dialysis days.
CRRT: Dosing is based on effluent flow rate and is intended as initial dosing in patients receiving CRRT; dosing may need adjusted based on residual renal function and patient’s clinical status.
CVVH/CVVHD/CVVHDF: IV:
Effluent flow rate ≤2 L/hour: 1.5 g every 12 hours.
Effluent flow rate 2.1 to 3 L/hour: 2 g every 12 hours.
Effluent flow rate 3.1 to 4 L/hour: 1.5 g every 8 hours.
Effluent flow rate ≥4.1 L/hour: 2 g every 8 hours.
No dosage adjustment necessary.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Endocrine & metabolic: Hypokalemia (2% to 11%)
Hepatic: Increased liver enzymes (2% to 16%)
1% to 10%:
Cardiovascular: Acute myocardial infarction (<4%), atrial fibrillation (5%), atrial flutter (<4%), bradycardia (<2%), heart failure (<2%), peripheral edema (<2%)
Dermatologic: Erythematous rash (<4%), pruritus (<2%), skin rash (3%)
Endocrine & metabolic: Hyperkalemia (<4%), hypervolemia (<2%), hypocalcemia (<4%), hypomagnesemia (5%)
Gastrointestinal: Abdominal pain (<4%), biliary colic (<2%), cholecystitis (<4%), cholelithiasis (<4%), Clostridioides difficile-associated diarrhea (<4%), constipation (3%), decreased appetite (<2%), diarrhea (4% to 9%), dysgeusia (<2%), nausea (2%), oral candidiasis (<4%), stomatitis (<2%), vomiting (2%), xerostomia (<2%)
Genitourinary: Hematuria (<2%)
Hematologic & oncologic: Increased INR (<4%), prolonged partial thromboplastin time (<4%), prolonged prothrombin time (<4%), thrombocytopenia (<4%), thrombocytosis (<4%)
Hypersensitivity: Hypersensitivity reaction (<2%)
Infection: Candidiasis (2%)
Local: Infusion-site reaction (4%)
Nervous system: Headache (2%), insomnia (<2%), restlessness (<2%), seizure (<4%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (<2%)
Renal: Acute interstitial nephritis (<4%)
Respiratory: Cough (2%), dyspnea (<2%), pleural effusion (<2%)
Miscellaneous: Fever (<2%)
Postmarketing:
Genitourinary: Urine discoloration
Hematologic & oncologic: Neutropenia
Severe hypersensitivity to cefiderocol, other beta-lactam antibacterial drugs, or any other component of the formulation.
Concerns related to adverse effects:
• Hypersensitivity: Serious, sometimes fatal, hypersensitivity reactions may occur. Use caution in patients with a history of penicillin, cephalosporin, or other beta-lactam sensitivity; cross-hypersensitivity may occur. If a hypersensitivity reaction occurs, discontinue therapy and institute supportive measures.
• Neurotoxicity: Neurological reactions have been reported with cephalosporins, including encephalopathy, coma, asterixis, neuromuscular excitability, myoclonia, and nonconvulsive status epilepticus. Risk may be increased in patients with a history of seizure disorders and/or in the presence of renal impairment; ensure dose adjusted for renal function. If neurotoxicity occurs, obtain a neurological evaluation to determine if cefiderocol should be discontinued.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides difficile–associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment (CrCl ≤60 mL/minute); dosage adjustments recommended. May increase risk of neurotoxicity.
• Seizure disorders: Use with caution in patients with a history of seizure disorder.
Other warnings/precautions:
• Appropriate use: Increased mortality was seen among critically ill patients receiving cefiderocol compared to recipients of best available therapy (most often containing colistin) for the treatment of carbapenem-resistant gram-negative bacterial infections, including pneumonia, bloodstream infection, and sepsis. The cause of the increase in mortality has not been established; closely monitor response to therapy in patients treated with cefiderocol.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Fetroja: 1 g (1 ea)
No
Solution (reconstituted) (Fetroja Intravenous)
1 g (per each): $279.41
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IV: Administer by intermittent IV infusion over 3 hours.
Pneumonia, hospital-acquired and ventilator-associated: Treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, caused by the following susceptible gram-negative microorganisms: Acinetobacter baumannii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens, in patients ≥18 years of age.
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Treatment of complicated urinary tract infections, including pyelonephritis, caused by the following susceptible gram-negative microorganisms: E. coli, K. pneumoniae, Proteus mirabilis, P. aeruginosa, and E. cloacae complex, in patients ≥18 years of age.
Urinary tract infection, acute uncomplicated cystitis or acute simple cystitis
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: Cephalosporins may increase nephrotoxic effects of Aminoglycosides. Cephalosporins may decrease serum concentration of Aminoglycosides. Risk C: Monitor
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Furosemide: May increase nephrotoxic effects of Cephalosporins. Risk C: Monitor
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Probenecid: May increase serum concentration of Cephalosporins. Risk C: Monitor
Sodium Picosulfate: Antibiotics may decrease therapeutic effects of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider Therapy Modification
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
Vitamin K Antagonists: Cephalosporins may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
In general, an increase in most types of birth defects or adverse maternal or fetal outcomes was not found following exposure to cephalosporins.
It is not known if cefiderocol is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Monitor renal function. Observe for signs and symptoms of anaphylaxis during first dose.
Cefiderocol is a siderophore cephalosporin. A catechol side chain promotes formation of chelated complexes with ferric iron, allowing use of iron transport systems to deliver cefiderocol across the outer membrane of gram-negative bacilli. The cephalosporin moiety binds to penicillin-binding proteins which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis.
Distribution: Vd: 18 (±3.36) L.
Protein binding: 40% to 60% (primarily to albumin).
Metabolism: Minimal.
Half-life elimination: 2 to 3 hours.
Excretion: Urine: 98.6% (90.6% as unchanged drug); feces: 2.8%.
Altered kidney function: AUC increased 1.37-, 2.35-, 3.21-, and 4.69-fold in patients with CrCl 60 to 89 mL/minute, 30 to 59 mL/minute, 15 to 29 mL/minute, and <15 mL/minute, respectively, compared to patients with CrCl 90 to 119 mL/minute. Patients with CrCl ≥120 mL/minute experience increased cefiderocol clearance. Approximately 60% of cefiderocol is removed by a 3- to 4-hour hemodialysis session.
Anti-infective considerations:
Parameters associated with efficacy: Time dependent; associated with time free drug concentration (fT) > minimum inhibitory concentration. Goal: ≥ ~75% (range 55% to 88%) (Katsube 2019; Nakamura 2019; Principe 2022).
Expected drug exposure in patients with normal renal function:
Adults: Cmax (peak): IV:
Single dose: 2 g IV: 156 mcg/mL (Saisho 2018).
Steady state: 2 g every 8 hours: 153 mcg/mL (Saisho 2018).
