Cefoxitin

Cefoxitin is a parenteral cephamycin, classed with second-generation cephalosporins, with activity against anaerobes including Bacteroides fragilis and stability to many beta-lactamases. It is used mainly for surgical prophylaxis, pelvic infection and mixed intra-abdominal infection, and for rapidly growing nontuberculous mycobacteria.

Classification. Beta-lactam, cephamycin (methoxy group at C-7).

Mechanism. Blocks penicillin-binding proteins; stable to many ESBL and other beta-lactamases, though it induces AmpC production in some Enterobacterales.

Spectrum. MSSA (not MRSA), streptococci, Escherichia coli, Klebsiella, Proteus, Bacteroides fragilis (resistance is rising), other anaerobes and Neisseria gonorrhoeae. Not active against Enterococcus, Pseudomonas or Enterobacter with inducible AmpC. Variable activity against ESBL-producing Escherichia coli.

Pharmacokinetics. IV (IM is painful). Half-life 40 to 60 minutes, so redosing for surgical prophylaxis is at 2 hours. About 85% excreted unchanged in urine.

No loading dose. Maximum 12 g daily.

Mild to moderate infection. 1 to 2 g IV every 6 to 8 hours.

Severe or life-threatening infection. 2 g IV every 4 to 6 hours.

Surgical prophylaxis (colorectal, appendicectomy, gynaecological). 1 to 2 g IV within 60 minutes before incision, repeated every 2 hours during surgery.

Pelvic inflammatory disease, inpatient. Cefoxitin 2 g IV every 6 hours with doxycycline 100 mg every 12 hours; continue 24 to 48 hours after clinical improvement, then complete 14 days with oral doxycycline (plus metronidazole if abscess or anaerobic infection is suspected).

Mycobacterium abscessus and rapidly growing mycobacteria (specialist use). 200 mg/kg/day divided every 6 to 8 hours, maximum 12 g daily, in multidrug combination for at least 2 weeks of the initial phase.

Children. 80 to 160 mg/kg/day divided every 4 to 6 hours, maximum 12 g daily. Surgical prophylaxis 30 to 40 mg/kg within 60 minutes before incision.

Alternatives. Cefazolin plus metronidazole, amoxicillin clavulanate, piperacillin tazobactam, ceftriaxone plus metronidazole.

Contraindications. Cephalosporin hypersensitivity.

Adverse effects. Diarrhoea, rash, phlebitis, Clostridioides difficile infection. Serious: anaphylaxis, severe cutaneous reactions, haemolytic anaemia, cytopenias, eosinophilia, interstitial nephritis, seizures in renal failure.

Laboratory interference. Cefoxitin causes a spurious rise in serum creatinine on the Jaffe method, and a positive direct Coombs test.

Interactions. Probenecid raises levels; loop diuretics and aminoglycosides increase nephrotoxicity; warfarin INR rise; oral typhoid vaccine.

Common prescribing errors. Using it for Enterobacter or Pseudomonas infection, assuming reliable cover for B. fragilis, missing the 2-hour redosing in long surgery, and misreading creatinine.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: reduce by kidney function. - Kidney impairment: creatinine clearance 30 to 50 mL/min 1 to 2 g every 8 to 12 hours; 10 to 29 mL/min 1 to 2 g every 12 to 24 hours; 5 to 9 mL/min 500 mg to 1 g every 12 to 24 hours; under 5 mL/min 500 mg to 1 g every 24 to 48 hours. Haemodialysis: 1 to 2 g after each session. - Liver impairment: no adjustment.

Preparation. IV push: reconstitute 1 g with 10 mL water for injection and inject over 3 to 5 minutes. Infusion: dilute in 50 to 100 mL of 0.9% sodium chloride or 5% glucose over 30 minutes.

Baseline and monitoring. - Baseline: allergy history, creatinine (interpret with the Jaffe interference in mind), cultures, full blood count. - During treatment: creatinine and full blood count twice weekly; liver tests in prolonged courses. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, severe cutaneous reaction, haemolysis or cytopenia.

Referral and escalation. Involve infectious diseases for rapidly growing mycobacterial infection, pelvic abscess and failure to respond at 48 to 72 hours.