Efepime

Approved Indications:

• Complicated Intra-abdominal Infections
  (in combination with metronidazole) in adults and children ≥2 months
• Complicated Urinary Tract Infections (UTIs)
  including pyelonephritis
• Hospital-acquired Pneumonia (HAP)
  including ventilator-associated pneumonia
• Febrile Neutropenia
  empiric treatment of fever in neutropenic patients
• Skin and Skin Structure Infections (SSSIs)
  caused by susceptible bacteria
• Uncomplicated UTIs
  including cystitis
• Community-acquired Pneumonia (CAP)
  due to Streptococcus pneumoniae or Haemophilus influenzae
• Bacteremia/Septicemia
  due to Gram-negative or Gram-positive organisms
• Meningitis (off-label use)
  particularly in hospital-acquired or healthcare-associated infections

Adults (≥18 years):

• Pneumonia / UTIs / SSSIs / Febrile Neutropenia:
  1–2 g IV every 8–12 hours for 7–10 days
• Complicated Intra-abdominal Infections:
  2 g IV every 8 hours + metronidazole for 7–10 days
• Febrile Neutropenia:
  2 g IV every 8 hours
• Empiric Therapy for Sepsis / Meningitis (off-label):
  2 g IV every 8 hours

Pediatrics (2 months to 16 years):

• 50 mg/kg IV every 8–12 hours, up to a max of 2 g per dose

Renal Impairment (adjust based on creatinine clearance):

• CrCl 30–60 mL/min: 1 g every 12 hours
• CrCl 11–29 mL/min: 1 g every 24 hours
• CrCl ≤10 mL/min: 500 mg every 24 hours
• Hemodialysis: 1 g post-dialysis

Administration Route:

• IV infusion over 30 minutes or IM injection (only for mild-moderate infections)
• Use reconstituted solution immediately or store per labeling instructions

Cefepime Hydrochloride exerts its bactericidal activity by inhibiting bacterial cell wall synthesis. It binds to and inactivates penicillin-binding proteins (PBPs), crucial enzymes involved in the terminal stages of peptidoglycan cross-linking within the bacterial cell wall. This inhibition disrupts cell wall integrity, leading to osmotic instability and lysis of the bacterial cell. Cefepime has enhanced stability against many β-lactamases, including extended-spectrum β-lactamases (ESBLs), and exhibits broad-spectrum activity against both Gram-positive and Gram-negative pathogens, including Pseudomonas aeruginosa.

• Absorption: Not orally bioavailable; administered parenterally
• Distribution: Widely distributed in body tissues and fluids, including lungs, peritoneal fluid, urine, bile, and cerebrospinal fluid (especially during meningitis)
• Protein Binding: ~16–20%
• Half-life: ~2 hours in adults with normal renal function
• Metabolism: Minimal hepatic metabolism
• Excretion: Primarily renal (≥85% unchanged in urine)
• Time to Peak Concentration (IV): Immediate post-infusion
• Dialyzable: Yes, significant clearance via hemodialysis

• Pregnancy:
  Classified as Pregnancy Category B (no adequate and well-controlled studies in pregnant women; animal studies show no harm)
  Should only be used during pregnancy if clearly needed.
• Lactation:
  Cefepime is excreted in low levels in breast milk.
  Although generally considered safe, monitor breastfed infants for gastrointestinal disturbances (e.g., diarrhea, candidiasis).

• Primary Class: Fourth-Generation Cephalosporin Antibiotic
• Subclass: Beta-lactam Antibacterial
• Generation: 4th generation (broadest spectrum of all cephalosporins)

• Known hypersensitivity to cefepime, other cephalosporins, or β-lactam antibiotics
• Immediate-type hypersensitivity reactions to penicillins
• Severe anaphylactic reactions to other beta-lactams
• History of seizures or CNS disorders with beta-lactam use (use with caution)

• Neurotoxicity:
  Can cause encephalopathy, seizures, confusion, especially in renal impairment or elderly
• Renal Dose Adjustment:
  Required to prevent toxicity in patients with impaired kidney function
• Superinfection:
  Prolonged use may lead to fungal or resistant bacterial overgrowth
• Hypersensitivity Reactions:
  Cross-reactivity with penicillins possible; monitor closely
• Clostridioides difficile-associated diarrhea (CDAD):
  May occur during or after treatment—discontinue if suspected
• Hematologic Monitoring:
  Prolonged therapy may cause neutropenia, anemia, or thrombocytopenia

Common:

• Gastrointestinal: Diarrhea, nausea, vomiting
• CNS: Headache, dizziness
• Skin: Rash, pruritus, urticaria
• Injection Site: Pain, inflammation

Serious:

• Seizures, encephalopathy, myoclonus (especially in renal failure)
• Anaphylaxis, bronchospasm
• Stevens-Johnson syndrome (rare)
• C. difficile–associated diarrhea
• Hematologic: Neutropenia, eosinophilia, leukopenia

Onset & Severity:

• CNS effects typically occur within 1–5 days in renal impairment
• Allergic reactions may occur at any time, even after first dose

• Aminoglycosides:
  Increased nephrotoxicity risk—monitor renal function closely
• Loop Diuretics (e.g., furosemide):
  Potentiates nephrotoxic risk when co-administered
• Probenecid:
  Can reduce renal clearance of cephalosporins
• Live Vaccines (e.g., Typhoid):
  May reduce vaccine effectiveness
• Laboratory Interference:
  May cause false-positive Coombs' test and urine glucose tests (Clinitest)

Enzyme Interactions:
Cefepime is not metabolized via CYP450, so it has low risk of hepatic enzyme-mediated drug interactions.

• Neurotoxicity Warning Strengthened:
  Clinical guidelines and drug safety authorities have emphasized the importance of renal dose adjustments to minimize CNS toxicity.
• Meningitis Use in NICUs:
  Recognized in off-label protocols for hospital-acquired neonatal meningitis caused by multidrug-resistant Gram-negative bacilli.
• Dose Optimization for Sepsis (2023):
  International guidelines recommend extended-infusion dosing for critically ill patients to improve pharmacodynamic exposure.

• Powder for Injection (vials):
  Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C
• Reconstituted Solutions (IV):
  Stable for up to 24 hours at room temperature or 7 days refrigerated at 2°C to 8°C
• Protection:
  Protect from light and freezing.
• Handling:
  Shake well before use. Discard if the solution is cloudy or contains particulates.