Cefoperazone

Cefoperazone is a parenteral third-generation cephalosporin with antipseudomonal activity and extensive biliary excretion. It is used mainly in some regions for biliary, abdominal and hospital-acquired Gram-negative infection and is often supplied in combination with sulbactam.

Classification. Beta-lactam, third-generation cephalosporin with an N-methylthiotetrazole side chain.

Mechanism. Blocks penicillin-binding proteins; sulbactam, when combined, adds activity against some beta-lactamase producers and Acinetobacter.

Spectrum. Pseudomonas aeruginosa (less active than ceftazidime), Enterobacterales without ESBL, streptococci, MSSA (moderate), Haemophilus, Neisseria, and some anaerobes. Not active against MRSA, Enterococcus or ESBL and carbapenemase producers.

Pharmacokinetics. IV or IM. Half-life about 2 hours. Protein binding 90%. About 70 to 80% eliminated in bile and 20 to 30% in urine, so high bile levels and little kidney dependence.

No loading dose. Maximum 12 g daily in adults.

Adults. - Moderate infection: 2 to 4 g daily divided every 12 hours. - Severe infection or Pseudomonas: 6 to 12 g daily divided every 8 to 12 hours. - Cefoperazone sulbactam combination (1:1 or 2:1), where supplied: 2 to 4 g of the combination daily in two divided doses; severe infection up to 8 g daily; maximum sulbactam 4 g daily.

Children. 50 to 200 mg/kg/day divided every 8 to 12 hours; maximum 12 g daily. Neonates: 50 mg/kg every 12 hours with bilirubin and coagulation monitoring.

Alternatives. Ceftazidime, cefepime, piperacillin tazobactam, meropenem.

Contraindications. Cephalosporin hypersensitivity.

Adverse effects. Diarrhoea, rash, phlebitis, eosinophilia, raised liver enzymes. Serious: hypoprothrombinaemia and bleeding, haemolytic anaemia, anaphylaxis, severe skin reactions, Clostridioides difficile infection, neutropenia.

Alcohol. Disulfiram-like reaction; avoid alcohol during treatment and for 5 days afterwards.

Interactions. Warfarin and other anticoagulants (bleeding), aminoglycosides (physical incompatibility), probenecid, oral typhoid vaccine.

Common prescribing errors. Prolonged courses without vitamin K, use in cholestasis without dose reduction, and giving alcohol-containing medicines.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults and malnourished: bleeding risk; give vitamin K 10 mg weekly in prolonged courses. - Kidney impairment: no change; limit to 4 g daily in severe impairment. - Liver impairment and biliary obstruction: half-life rises; limit to 4 g daily, and to 2 g daily when kidney failure coexists.

Preparation. IV: dissolve in water for injection and infuse over 15 to 60 minutes in 0.9% sodium chloride or 5% glucose. IM: reconstitute with 1% lidocaine.

Baseline and monitoring. - Baseline: allergy history, cultures, prothrombin time, liver tests, creatinine. - During treatment: prothrombin time twice weekly, full blood count, liver tests weekly. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, bleeding, haemolysis or severe skin reaction.

Referral and escalation. Seek hepatology and infectious diseases input for biliary sepsis, cholestasis and failure at 48 to 72 hours.