Cefotaxime

Cefotaxime is a parenteral third-generation cephalosporin with strong activity against meningococci, pneumococci, Haemophilus and non-ESBL Enterobacterales. Unlike ceftriaxone, it does not displace bilirubin or precipitate with calcium, so it is preferred in neonates.

Classification. Beta-lactam, third-generation cephalosporin.

Mechanism. Blocks penicillin-binding proteins; stable to many beta-lactamases but not to ESBLs and AmpC.

Spectrum. Streptococci, pneumococci (including intermediate penicillin resistance), meningococci, Haemophilus influenzae, Neisseria gonorrhoeae, Enterobacterales without ESBL, and some anaerobes. Weak against Pseudomonas, Enterococcus, Listeria and MRSA.

Pharmacokinetics. IV or IM. Half-life about 1 hour; active metabolite desacetylcefotaxime has a half-life of about 1.5 hours. Good CSF penetration with inflamed meninges. Eliminated by kidney and, in part, by liver.

No loading dose. Maximum 12 g daily.

Adults. - Moderate infection (pneumonia, urinary, skin, pelvic): 1 g IV or IM every 8 to 12 hours. - Severe infection or bacteraemia: 2 g IV every 6 to 8 hours. - Bacterial meningitis: 2 g IV every 4 to 6 hours (8 to 12 g daily). Duration: meningococcus 7 days; pneumococcus 10 to 14 days; Haemophilus 7 to 10 days; Gram-negative bacilli 21 days. - Surgical prophylaxis: 1 g IV at induction.

Children. 50 mg/kg every 6 to 8 hours (maximum 12 g daily); meningitis 50 mg/kg every 6 hours.

Neonates. 50 mg/kg every 12 hours in the first week and every 8 hours from 7 to 28 days; meningitis 50 mg/kg every 6 to 8 hours.

Alternatives. Ceftriaxone (once or twice daily), cefepime, meropenem for ESBL.

Contraindications. Cephalosporin hypersensitivity.

Adverse effects. Diarrhoea, rash, phlebitis, Clostridioides difficile infection. Serious: anaphylaxis, severe cutaneous reactions, haemolytic anaemia, neutropenia, thrombocytopenia, interstitial nephritis, encephalopathy in renal failure. Rapid IV bolus through a central line has been linked to arrhythmias.

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

Common prescribing errors. Omitting ampicillin cover for Listeria in older adults, ESBL assumption, giving a rapid bolus, and not reducing the dose in renal failure.

Special groups. - Pregnancy and breastfeeding: acceptable. - Neonates: no calcium or bilirubin interaction; first choice cephalosporin in the first month. - Older adults: reduce by kidney function. - Kidney impairment: creatinine clearance under 20 mL/min halve the daily dose after the first full dose; haemodialysis give after the session. - Liver impairment: no adjustment; in combined severe liver and kidney failure reduce the dose.

Preparation. IV bolus: reconstitute 1 g in 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 20 to 60 minutes. IM: reconstitute with 1% lidocaine (maximum 1 g at one site).

Baseline and monitoring. - Baseline: allergy history, cultures before first dose, creatinine, 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 skin reaction, cytopenia or unexplained encephalopathy.

Referral and escalation. Infectious diseases and neurology input for meningitis that fails to improve at 48 hours, neonatal meningitis and ventriculitis.