Cefotetan

Cefotetan is a parenteral cephamycin with a long half-life, used for twice-daily dosing in pelvic and mixed intra-abdominal infection and for surgical prophylaxis. Its N-methylthiotetrazole side chain brings bleeding and alcohol-intolerance risks.

Classification. Beta-lactam, cephamycin (second-generation range).

Mechanism. Blocks penicillin-binding proteins; stable to many beta-lactamases, including some ESBLs.

Spectrum. Streptococci (not enterococci), MSSA (less active than cefazolin), Escherichia coli, Klebsiella, Proteus, Haemophilus, Neisseria and many anaerobes. Bacteroides fragilis resistance is increasing and cefotetan is less reliable than cefoxitin or metronidazole. Not active against MRSA, Pseudomonas or Enterobacter with inducible AmpC.

Pharmacokinetics. IV or IM. Half-life 3 to 4.5 hours. Protein binding about 85%. About 50 to 80% excreted unchanged in urine.

No loading dose. Maximum 6 g daily in adults.

Adults. - Skin, urinary, lower respiratory, gynaecological and intra-abdominal infection: 1 to 2 g IV or IM every 12 hours for 5 to 14 days. - Severe or life-threatening infection: 2 to 3 g IV every 12 hours. - Inpatient pelvic inflammatory disease: 2 g IV every 12 hours with doxycycline 100 mg every 12 hours until 24 to 48 hours after improvement, then oral doxycycline to complete 14 days. - Surgical prophylaxis: 1 to 2 g IV as a single dose 30 to 60 minutes before incision (colorectal, hysterectomy, biliary).

Children (specialist use, limited licensing). 20 to 40 mg/kg every 12 hours, maximum 3 g a dose.

Alternatives. Cefoxitin, cefazolin plus metronidazole, piperacillin tazobactam, ceftriaxone plus metronidazole.

Contraindications. Cephalosporin hypersensitivity; previous immune haemolytic anaemia with cefotetan.

Adverse effects. Diarrhoea, rash, phlebitis, Clostridioides difficile infection. Serious: anaphylaxis, immune haemolytic anaemia (reported more often than with other cephalosporins and can be fatal), hypoprothrombinaemia and bleeding, thrombocytopenia, interstitial nephritis, seizures in renal failure.

Alcohol. Disulfiram-like reaction (flushing, palpitations, vomiting); avoid alcohol during treatment and for 3 days afterwards.

Interactions. Warfarin and other anticoagulants (bleeding), probenecid, loop diuretics and aminoglycosides (nephrotoxicity), oral typhoid vaccine.

Common prescribing errors. Not giving vitamin K in prolonged courses of malnourished or elderly patients, using it for Pseudomonas, and not adjusting for renal function.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: bleeding risk; reduce by kidney function. - Kidney impairment: creatinine clearance over 30 mL/min every 12 hours; 10 to 30 mL/min usual dose every 24 hours; under 10 mL/min usual dose every 48 hours. Haemodialysis: one quarter of the usual dose every 24 hours on non-dialysis days and half the usual dose on dialysis days. - Liver impairment: no adjustment. - Region: availability in East Africa is limited.

Preparation. IV: reconstitute 1 g with 10 mL water for injection; inject over 3 to 5 minutes or infuse over 30 minutes in 50 to 100 mL of 0.9% sodium chloride or 5% glucose. IM: reconstitute with 1% lidocaine.

Baseline and monitoring. - Baseline: allergy history, creatinine, full blood count, prothrombin time. - During treatment: prothrombin time weekly in courses over 5 days or when risk factors exist; full blood count and creatinine twice weekly; direct Coombs test if unexplained anaemia. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, haemolysis, bleeding, or a disulfiram-like reaction.

Referral and escalation. Seek haematology input for haemolytic anaemia and infectious diseases for pelvic abscess and failure at 48 to 72 hours.