Cefoperazone

# Cefoperazone ## Overview Cefoperazone is a third-generation cephalosporin with broad-spectrum Gram-negative coverage, including *Pseudomonas aeruginosa*. It is commonly formulated with sulbactam (a beta-lactamase inhibitor) as cefoperazone-sulbactam. It is primarily excreted via bile, not kidneys. ## Primary Indications - Complicated intra-abdominal infections - Complicated urinary tract infections - Hospital-acquired pneumonia (including ventilator-associated) - Febrile neutropenia (in combination) - Septicemia - Skin and soft tissue infections ## Adult Dosing - **Usual dose:** Cefoperazone 2–4 g/day divided every 12 hours (e.g., 1–2 g q12h) - **Severe infections:** Up to 6 g/day (2 g q8h) - **Maximum daily dose:** 12 g/day (rarely used; local protocol) *Note: When combined with sulbactam, the cefoperazone component follows same dosing; sulbactam maximum is 4 g/day.* ## Pediatric Dosing - **General:** 50–200 mg/kg/day divided every 8–12 hours - **Maximum single dose:** Not well defined; follow local protocol (often up to 2 g per dose in older children) - **Neonates:** Safety not established; use only if benefit outweighs risk ## Dose Adjustments - **Hepatic impairment:** Dose reduction (e.g., 25–50% reduction) may be needed due to biliary excretion; monitor PT/INR - **Renal impairment:** No significant dose adjustment required because minimal renal excretion - **Hemodialysis:** No supplemental dose typically needed ## Contraindications - Hypersensitivity to cephalosporins or penicillins (cross-reactivity risk ~10%) - Severe immediate allergic reaction history ## Adverse Effects - **Common:** Diarrhea, nausea, rash, elevated liver enzymes - **Serious:** Hypoprothrombinemia/bleeding (due to NMTT side chain), disulfiram-like reaction with alcohol, pseudomembranous colitis, anaphylaxis ## Key Drug Interactions - **Alcohol:** Disulfiram-like reaction (flushing, vomiting, tachycardia) – avoid for 48–72 hours after last dose - **Anticoagulants (warfarin, etc.):** Increased PT/INR and bleeding risk - **Vitamin K antagonists:** Enhanced hypoprothrombinemia - **Aminoglycosides:** Synergy but monitor nephrotoxicity ## Monitoring - Prothrombin time / INR (especially in malnourished, hepatic impairment, or prolonged therapy) - Signs of bleeding (bruising, petechiae) - Liver function tests (periodic) - For combination with sulbactam: no additional monitoring beyond standard ## Clinical Pearls - Contains a methylthiotetrazole (NMTT) side chain → **risk of hypoprothrombinemia** and disulfiram reactions - Prophylactic vitamin K (10 mg IM/IV weekly) may be considered in high-risk patients (e.g., malnutrition, prolonged therapy) - Avoid all alcohol (including mouthwash, elixirs) during therapy and for at least 3 days after - Biliary excretion means unchanged drug in bile – good for biliary infections but caution in hepatic obstruction --- *This summary is for educational purposes only. Always verify current prescribing information from an authoritative drug reference before making clinical decisions. Dosing may vary by local protocol, patient factors, and formulary availability.*