cefiderocol

General

Pronunciation:
sef-i-der-oh-kol

Trade Name(s)

  • Fetroja

Ther. Class.

anti-infectives

Pharm. Class.

cephalosporin derivatives

Indications

  • Complicated urinary tract infections (cUTI), including pyelonephritis, in patients who have limited or no alternative treatment options.
  • Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.

Action

Functions as a siderophore and binds to extracellular free ferric iron. Iron transport systems then deliver cefiderocol across the outer membrane of gram-negative bacilli where it binds to the bacterial cell wall membrane, causing cell death.

Therapeutic Effect(s):

Bactericidal action against susceptible bacteria.

Spectrum:

Active against the following gram-negative bacilli: Acinetobacter baumannii , Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Some distribution to extracellular tissues.

Metabolism and Excretion: Undergoes minimal metabolism by liver; primarily excreted in urine (99%; 91% as unchanged drug).

Half-life: 2–3 hr.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
IVrapidend of infusion8 hr

Contraindication/Precautions

Contraindicated in:

  • Known serious hypersensitivity to cefiderocol or other beta-lactams.

Use Cautiously in:

  • Carbapenem-resistant gram-negative bacterial infections, including nosocomial pneumonia, bloodstream infections, and sepsis (↑ risk of mortality);
  • Seizure disorders;
  • Renal impairment (dosage ↓ required for CCr <60 mL/min);
  • OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
  •  Lactation: Use while breast feeding only if potential maternal benefit justifies potential risk to infant;
  • Pedi:   Safety and effectiveness not established in children;
  • Geri:   Dose adjustment may be necessary in older adults for age-related ↓ in renal function.

Adverse Reactions/Side Effects

Derm: rash

EENT: thrush

F and E: hypokalemia

GI: CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation, diarrhea, ↑ liver enzymes, nausea, vomiting

GU: candiduria, vaginal candidiasis

Local: infusion site reactions

Neuro: SEIZURES, headache

Resp: cough

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

IV (Adults): CCr ≥120 mL/min– 2 g every 6 hr for 7–14 days;  CCr 60–119 mL/min– 2 g every 8 hr for 7–14 days.

Renal Impairment 
IV (Adults): CCr 30–59 mL/min– 1.5 g every 8 hr for 7–14 days;  CCr 15–29 mL/min– 1 g every 8 hr for 7–14 days;  CCr <15 mL/min (with or without hemodialysis)– 0.75 g every 12 hr for 7–14 days (in patients receiving hemodialysis, administer dose immediately following hemodialysis session);  Continuous renal replacement therapy– Effluent flow rate ≥4.1 L/hr: 2 g every 8 hr for 7–14 days; effluent flow rate 3.1–4 L/hr: 1.5 g every 8 hr for 7–14 days; Effluent flow rate 2.1–3 L/hr: 2 g every 12 hr for 7–14 days; Effluent flow rate ≤2 L/hr: 1.5 g every 12 hr for 7–14 days.

Availability

Lyophilized powder for injection: 1 g/vial

Assessment

  • Assess for infection (vital signs, appearance of urine, WBC) at beginning of and during therapy. Monitor clinical response to therapy closely.
  • Obtain a history before initiating therapy to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response.
  • Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Notify health care professional immediately if these occur.
  • Obtain specimens for culture and sensitivity prior to therapy. First dose may be given before receiving results.
  • Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of Clostridioides difficile-associated diarrhea (CDAD). May begin up to several wk following cessation of therapy.

Lab Test Considerations:

May cause false-positive results in dipstick tests (urine protein, ketones, occult blood). Use alternate clinical laboratory methods of testing to confirm positive tests.

Potential Diagnoses

Implementation

  • Intermittent Infusion:   Reconstitution: Reconstitute with 10 mL 0.9% NaCl or D5W; gently shake to dissolve. Allow vial to stand until foaming has disappeared; usually 2 min. Dilution:  Withdraw appropriate volume from vial and dilute in 100 mL 0.9% NaCl or D5W immediately after reconstitution. Solution is clear and colorless; do not administer solutions that are discolored, cloudy, or contain particulate matter. Reconstituted solution is stable for 1 hr at room temperature. Solution diluted in IV bag is stable for up to 6 hr at room temperature and 24 hr if refrigerated and protected from light.
  • Rate: Infusion must be completed with 6 hr.

Patient/Family Teaching

  • Explain purpose of cefiderocol and the importance of completing full course of therapy to patient. Skipping doses or not completing full course of therapy may decrease effectiveness of the immediate treatment and increase the likelihood that bacteria will develop resistance and will not be treatable by cefiderocol or other antibacterial drugs in the future.
  • Advise patient to report the signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools) and allergy.
  • Instruct patient to notify health care professional immediately if diarrhea, abdominal cramping, fever, or bloody stools or signs and symptoms of anaphylaxis occur and not to treat with antidiarrheals without consulting health care professional.
  • Inform patient of risk of seizures, especially in patient with a seizure disorder. Advise patient to notify health care professional immediately if seizure occurs.
  • Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

Resolution of the signs and symptoms of infection.

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