Cefazolin

Cefazolin is a parenteral first-generation cephalosporin and the drug of choice for surgical prophylaxis and for many serious MSSA infections. It is a first-line alternative to anti-staphylococcal penicillins.

Classification. Beta-lactam, first-generation cephalosporin.

Mechanism. Blocks penicillin-binding proteins and cell wall synthesis; time-dependent killing.

Spectrum. MSSA, streptococci, and some Escherichia coli, Klebsiella and Proteus mirabilis. Poor activity against anaerobes, Haemophilus, MRSA, Enterococcus and Pseudomonas. Very high bacterial burden may reduce activity because of a staphylococcal beta-lactamase inoculum effect; clinical significance is debated.

Pharmacokinetics. IV or IM. Half-life 1.5 to 2 hours. Protein binding 80%. Eliminated by the kidney. Poor CNS penetration; do not use for meningitis.

No loading dose except surgical prophylaxis. Maximum 12 g daily.

Moderate to severe infection (skin, soft tissue, bone, joint, respiratory, urinary). 1 to 2 g IV every 8 hours.

MSSA bacteraemia and endocarditis, bone and joint infection. 2 g IV every 8 hours (some services use 2 g every 6 hours in high-burden infection or continuous infusion); bacteraemia at least 14 days from first negative blood culture, native valve endocarditis 4 to 6 weeks, osteomyelitis 6 weeks.

Surgical prophylaxis. 2 g IV within 60 minutes before incision (3 g if body weight 120 kg or more); repeat 2 g if surgery exceeds 4 hours or blood loss over 1.5 litres. For caesarean birth give before skin incision.

Children. 25 to 50 mg/kg every 8 hours (maximum 2 g a dose); severe infection 100 to 150 mg/kg/day divided every 8 hours; maximum 6 g daily. Prophylaxis 30 mg/kg (maximum 2 g) within 60 minutes before incision. Neonates under 7 days: 25 mg/kg every 12 hours; 7 days and over: every 8 hours.

Alternatives. Flucloxacillin, nafcillin or oxacillin; cefuroxime; vancomycin in MRSA or severe beta-lactam allergy.

Contraindications. Cephalosporin hypersensitivity. Cefazolin has a unique side chain with low cross-reactivity with other beta-lactams, so it can often be used in non-severe penicillin allergy.

Adverse effects. Diarrhoea, rash, phlebitis, Clostridioides difficile infection. Serious: anaphylaxis, severe cutaneous reactions, haemolytic anaemia, neutropenia, thrombocytopenia, seizures in renal failure, interstitial nephritis. Rare hypoprothrombinaemia and disulfiram-like reaction linked to the methylthiadiazole side chain.

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

Common prescribing errors. Giving it for meningitis or MRSA, omitting the weight-based 3 g prophylaxis dose, repeating prophylaxis too late, and not reducing the dose in renal failure.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: reduce by kidney function. - Kidney impairment: creatinine clearance 55 mL/min or more no change; 35 to 54 mL/min full dose with interval 8 hours or longer; 11 to 34 mL/min half dose every 12 hours; 10 mL/min or less half dose every 18 to 24 hours. Haemodialysis: 2 g after dialysis three times weekly (or 500 mg to 1 g every 24 hours). - Liver impairment: no adjustment. - Obesity: weight-based prophylaxis; full doses in treatment.

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. IM: reconstitute 1 g with 2.5 mL water or 1% lidocaine.

Baseline and monitoring. - Baseline: allergy history, creatinine, cultures, full blood count. - During treatment: creatinine twice weekly, full blood count weekly beyond 2 weeks, liver tests in prolonged courses; INR if on warfarin. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, severe rash, unexplained haemolysis or cytopenia, and seizures.

Referral and escalation. Infectious diseases for every Staphylococcus aureus bacteraemia, endocarditis, implant infection and persistent positive cultures at 72 hours.