Cefixime

Cefixime is an oral third-generation cephalosporin with good Gram-negative and Haemophilus activity but weak staphylococcal activity. It is used for urinary, respiratory, ear and enteric infection and as an oral option in some gonorrhoea and typhoid regimens.

Classification. Beta-lactam, third-generation cephalosporin, oral.

Mechanism. Blocks penicillin-binding proteins; stable to many beta-lactamases of Haemophilus, Moraxella and Enterobacterales, but not to ESBLs.

Spectrum. Streptococcus pyogenes, pneumococci (modest, penicillin-nonsusceptible strains unreliable), Haemophilus influenzae, Moraxella, Neisseria gonorrhoeae, Salmonella and non-ESBL Escherichia coli, Klebsiella and Proteus. Not active against staphylococci, enterococci, Pseudomonas or anaerobes.

Pharmacokinetics. Oral bioavailability 40 to 50%, not affected by food. Half-life 3 to 4 hours. About 50% excreted unchanged in urine; long half-life allows once-daily dosing.

No loading dose. Maximum 400 mg daily in most indications; 800 mg single dose in gonorrhoea.

Adults. - Uncomplicated urinary tract infection: 400 mg once daily for 3 to 7 days when susceptible. - Pharyngitis, sinusitis, acute bronchitis and otitis media: 400 mg once daily (or 200 mg every 12 hours) for 5 to 10 days. - Uncomplicated gonorrhoea (when ceftriaxone is unavailable): 800 mg as a single oral dose. Test for cure because failure rates are higher than with ceftriaxone. - Enteric fever (alternative where susceptible): 400 mg every 12 hours for 7 to 14 days.

Children 6 months and over. 8 mg/kg once daily or 4 mg/kg every 12 hours; maximum 400 mg daily. Enteric fever: 15 to 20 mg/kg/day divided every 12 hours.

Alternatives. Amoxicillin, cefpodoxime, ceftriaxone, azithromycin.

Contraindications. Cephalosporin hypersensitivity.

Adverse effects. Diarrhoea (common, dose-related), nausea, abdominal pain, rash, Clostridioides difficile infection. Serious: anaphylaxis, severe skin reactions, interstitial nephritis, haemolytic anaemia, cytopenias, hepatitis, seizures in renal failure.

Interactions. Warfarin (INR rise), carbamazepine (levels may rise), probenecid, oral typhoid vaccine.

Common prescribing errors. Using it for staphylococcal infection, as first-line therapy for gonorrhoea when resistance is known, and for severe typhoid or bacteraemia.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: reduce by kidney function. - Kidney impairment: creatinine clearance 21 to 60 mL/min give 75% of the usual dose; 20 mL/min or less give 50% of the usual dose; haemodialysis 50% of the usual dose, given after the session. - Liver impairment: no adjustment. - Region: resistance in Salmonella Typhi and gonococci is documented in several settings; check local susceptibility before use.

Formulations. Tablets 200 mg and 400 mg; dispersible tablets; suspension 100 mg in 5 mL. Take with or without food. Shake the suspension; discard after the labelled period.

Baseline and monitoring. - Baseline: allergy history, creatinine if risk of kidney disease. - During treatment: review at 48 to 72 hours; stool pattern. - No therapeutic drug monitoring.

Stop rules. Stop for hypersensitivity, severe diarrhoea with fever or blood, or jaundice.

Referral and escalation. Refer for persistent fever at 72 hours in enteric fever, failure of gonorrhoea treatment, and sepsis.