Cefuroxime

Cefuroxime is a second-generation cephalosporin with better Gram-negative and Haemophilus activity than first-generation agents. It is used orally as the axetil ester for respiratory and skin infection and Lyme disease, and intravenously for hospital pneumonia and surgical prophylaxis.

Classification. Beta-lactam, second-generation cephalosporin; oral prodrug cefuroxime axetil.

Mechanism. Blocks penicillin-binding proteins; stable to many staphylococcal and Haemophilus beta-lactamases.

Spectrum. MSSA, streptococci, pneumococci, Haemophilus influenzae, Moraxella, Neisseria, Borrelia burgdorferi, and some Escherichia coli, Klebsiella and Proteus. Not active against MRSA, Enterococcus, Pseudomonas, anaerobes, ESBL producers or atypical organisms.

Pharmacokinetics. Oral axetil bioavailability about 37% fasting and about 52% with food, so take with food. IV half-life about 1.2 hours. Eliminated by the kidney. CSF penetration is unreliable and treatment failure in meningitis has occurred.

No loading dose. Maximum 6 g IV daily and 1 g orally daily in adults.

Oral, adults. - Pharyngitis and tonsillitis: 250 mg every 12 hours for 5 to 10 days. - Sinusitis, acute bronchitis, exacerbation of COPD, uncomplicated skin infection and urinary infection: 250 to 500 mg every 12 hours for 5 to 7 days. - Early Lyme disease: 500 mg every 12 hours for 14 to 21 days.

IV or IM, adults. 750 mg every 8 hours; 1.5 g every 8 hours in severe infection (hospital pneumonia, intra-abdominal sepsis); bone and joint 1.5 g every 8 hours. Surgical prophylaxis: 1.5 g IV at induction, often with metronidazole 500 mg for abdominal or gynaecological procedures; repeat after 3 to 4 hours if surgery is prolonged.

Children. - Oral: 10 to 15 mg/kg every 12 hours; maximum 500 mg a dose. Under 2 years: 125 mg every 12 hours. - IV: 20 mg/kg every 8 hours (maximum 750 mg a dose); severe infection 50 to 100 mg/kg/day divided every 6 to 8 hours (maximum 6 g daily). - Not suitable for meningitis.

Alternatives. Amoxicillin clavulanate, ceftriaxone, doxycycline, cephalexin.

Contraindications. Cephalosporin hypersensitivity.

Adverse effects. Diarrhoea, nausea, rash, Clostridioides difficile infection, injection-site pain. Serious: anaphylaxis, severe skin reactions, interstitial nephritis, haemolytic anaemia, cytopenias, seizures in renal failure. A Jarisch-Herxheimer reaction may occur in Lyme disease.

Interactions. Antacids and H2-receptor antagonists reduce oral absorption; probenecid raises levels; loop diuretics and aminoglycosides increase nephrotoxicity; warfarin INR rise; oral typhoid vaccine.

Common prescribing errors. Using it for meningitis, giving tablets without food, crushing tablets (bitter taste), and not reducing dose in renal failure.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: reduce by kidney function. - Kidney impairment (IV): creatinine clearance over 20 mL/min no change; 10 to 20 mL/min 750 mg every 12 hours; under 10 mL/min 750 mg every 24 hours; haemodialysis dose after the session. Oral: creatinine clearance 10 to 29 mL/min once daily; under 10 mL/min every 48 hours. - Liver impairment: no adjustment.

Preparation. Tablets with food. IV: reconstitute with water for injection, give by slow injection over 3 to 5 minutes or infuse over 30 minutes. IM: reconstitute with 3 mL water for each 750 mg.

Baseline and monitoring. - Baseline: allergy history, creatinine, cultures. - During treatment: creatinine and full blood count in courses over 14 days; liver tests in prolonged therapy. - No therapeutic drug monitoring.

Stop rules. Stop for anaphylaxis, severe skin reaction, cytopenia or seizures.

Referral and escalation. Refer when there is no response in 48 to 72 hours, suspected CNS involvement, empyema, and disseminated Lyme disease.