Cefazone

Approved Indications:

• Lower Respiratory Tract Infections: Including pneumonia, bronchitis, and infected bronchiectasis.
• Urinary Tract Infections (UTIs): Including pyelonephritis and cystitis.
• Intra-abdominal Infections: Such as peritonitis, cholecystitis, and cholangitis.
• Skin and Soft Tissue Infections: Including cellulitis and wound infections.
• Septicemia (Bacteremia): Confirmed or suspected bloodstream infections caused by susceptible organisms.
• Bone and Joint Infections: Osteomyelitis and septic arthritis.
• Gynecological Infections: Including endometritis and pelvic inflammatory disease.
• Meningitis (off-label): Used in some settings when caused by susceptible Gram-negative organisms.
• Surgical Prophylaxis: To prevent postoperative infections in gastrointestinal and gynecologic procedures.

Route of Administration: Intravenous (IV) or Intramuscular (IM) injection

Adults:

• Standard Dose: 2–4 g/day in divided doses every 12 hours.
• Severe Infections: May require up to 8–12 g/day, divided every 8–12 hours.
• Meningitis (off-label): 3–4 g every 8 hours (up to 12 g/day IV).
• Surgical Prophylaxis: 1–2 g IV 30–90 minutes before incision; may repeat every 12 hours for up to 24 hours post-op.

Pediatric Patients:

• Neonates (<7 days old): 50–100 mg/kg/day in 2 divided doses.
• Infants & Children (>7 days): 100–200 mg/kg/day in 2–4 divided doses (max: 12 g/day).

Elderly:

• Same as adults, unless hepatic dysfunction is present.

Hepatic Impairment:

• Dose adjustment required due to biliary excretion. Use with caution; monitor liver function closely.
• Consider reducing dose or increasing dosing interval in severe hepatic dysfunction.

Renal Impairment:

• No significant dosage adjustment needed alone, but dose adjustment is required if combined hepatic and renal impairment is present.

Administration Notes:

• IM injections should be deep into a large muscle.
• IV bolus over 3–5 minutes or IV infusion over 15–30 minutes.
• Reconstituted solution must be used within the recommended time based on storage conditions.

Cefoperazone Sodium is a third-generation cephalosporin antibiotic that exerts its bactericidal action by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs), disrupting the final transpeptidation step in peptidoglycan synthesis of the bacterial cell wall. This leads to weakening and lysis of the bacterial cell. Cefoperazone is particularly active against a broad spectrum of Gram-negative bacteria, including Pseudomonas aeruginosa, and shows moderate activity against Gram-positive organisms. Its stability against many beta-lactamases enhances its efficacy in resistant infections.

• Absorption: Not absorbed orally; given parenterally (IV/IM).
• Distribution: Widely distributed in body fluids and tissues; penetrates well into bile, pleural fluid, and peritoneal fluid. CSF penetration is moderate.
• Protein Binding: High (approximately 90–95%).
• Metabolism: Not significantly metabolized.
• Half-Life: Approximately 1.7 hours in normal renal and hepatic function; prolonged in hepatic dysfunction.
• Excretion: Primarily via biliary route (70%), and to a lesser extent via renal route (30%).
• Special Consideration: High biliary excretion can lead to biliary sludging or cholestasis in prolonged high-dose therapy.

• Pregnancy Category: Category B (FDA). Animal studies show no risk; however, there are no adequate, well-controlled studies in pregnant women.
• Lactation: Cefoperazone is excreted in low concentrations in breast milk. While generally considered safe, monitor the infant for possible GI disturbances such as diarrhea or candidiasis. Use with caution in nursing mothers.

• Primary Class: Third-Generation Cephalosporin Antibiotic
• Subclassification: Anti-pseudomonal cephalosporin

• Known hypersensitivity to Cefoperazone or any β-lactam antibiotics (penicillins, cephalosporins).
• History of severe anaphylactic reaction to β-lactam antibiotics.
• Known hypersensitivity to sodium-containing formulations in sodium-restricted patients.

• Hypersensitivity Reactions: Risk of serious allergic reactions, including anaphylaxis, especially in β-lactam-sensitive individuals.
• Bleeding Tendency: May interfere with vitamin K synthesis due to suppression of gut flora; monitor prothrombin time, especially in patients with malnutrition, anticoagulant use, or hepatic disease.
• Superinfection: Prolonged use may result in fungal or bacterial superinfections, including Clostridioides difficile-associated diarrhea.
• Hepatic Dysfunction: Use with caution; monitor liver function.
• Renal Impairment with Hepatic Impairment: Dose adjustment needed.
• Sodium Load: Caution in patients requiring sodium restriction (e.g., CHF, hypertension).
• Use in Neonates: Monitor bilirubin levels; risk of kernicterus due to bilirubin displacement.

Common Adverse Effects:

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain.
• Hematologic: Eosinophilia, thrombocytopenia, transient leukopenia, prolonged prothrombin time.
• Hepatic: Transient elevation of liver enzymes (ALT, AST), cholestasis.
• Injection Site: Pain, induration, phlebitis (IV).

Serious Adverse Effects:

• Anaphylaxis
• Stevens-Johnson Syndrome
• Pseudomembranous colitis
• Hemorrhage due to hypoprothrombinemia

Rare Side Effects:

• Agranulocytosis
• Nephrotoxicity
• Convulsions (in high doses or renal impairment)

• Alcohol: Disulfiram-like reaction (nausea, flushing, tachycardia, hypotension).
• Anticoagulants (e.g., warfarin): Potentiated anticoagulant effect due to reduced vitamin K activity.
• Aminoglycosides: Increased nephrotoxicity when combined.
• Loop Diuretics: May increase nephrotoxicity risk when used together.
• Oral Contraceptives: May reduce effectiveness; consider backup contraception.

Enzyme System Involvement: Not metabolized via CYP450, but may affect vitamin K-dependent pathways indirectly.

• EMA & FDA: No recent major changes in approved indications or dosing guidelines.
• Global Guidelines: Continues to be included in hospital formularies for treatment of Gram-negative nosocomial infections, especially where Pseudomonas is a concern.
• Surveillance Updates: Rising resistance among Enterobacteriaceae; local antibiogram should guide use.
• WHO Recommendations: Suggest combination with sulbactam (Cefoperazone + Sulbactam) to expand spectrum and counter β-lactamase resistance.

• Dry Powder Vials:
• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Protect from moisture and excessive light.
• Reconstituted Solution:
• Stable for up to 24 hours at room temperature or 7 days under refrigeration (2°C–8°C).
• Do not freeze.
• Use freshly prepared solution for IV administration.
• Shake well before use; inspect visually for particulate matter or discoloration.