Cephalexin

Cephalexin is an oral first-generation cephalosporin used for skin and soft tissue infection, uncomplicated urinary infection and streptococcal pharyngitis, and for oral step-down after IV cefazolin.

Classification. Beta-lactam, first-generation cephalosporin.

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

Spectrum. MSSA, streptococci (not enterococci), Escherichia coli, Klebsiella and Proteus mirabilis (resistance is common in many settings). Poor activity against Haemophilus, anaerobes, MRSA, Enterococcus, Pseudomonas and ESBL producers.

Pharmacokinetics. Oral bioavailability about 90%, minimally affected by food. Half-life 0.5 to 1 hour. Over 90% excreted unchanged in urine, giving high urinary levels. Crosses the placenta and appears in breast milk in small amounts.

No loading dose. Maximum 4 g daily in adults.

Skin and soft tissue infection (non-purulent cellulitis, erysipelas, impetigo). 500 mg every 6 hours (or 1 g every 12 hours in adherence-limited cases) for 5 to 7 days.

Streptococcal pharyngitis. 500 mg every 12 hours for 10 days.

Acute uncomplicated cystitis. 500 mg every 12 hours for 5 to 7 days when the isolate is susceptible.

Bone and joint step-down, prosthetic joint suppression. 500 mg to 1 g every 6 to 8 hours as directed by a specialist after IV therapy.

Bacteriuria in pregnancy and recurrent UTI prophylaxis. Treatment 500 mg every 12 hours for 5 to 7 days; prophylaxis 125 to 250 mg at night.

Children. 25 to 50 mg/kg/day divided every 6 to 12 hours (pharyngitis and skin infection every 12 hours); severe infection up to 100 mg/kg/day every 6 hours; maximum 4 g daily.

Alternatives. Cefadroxil, flucloxacillin, amoxicillin clavulanate, clindamycin, co-trimoxazole for suspected MRSA.

Contraindications. Cephalosporin hypersensitivity. Use with caution in penicillin allergy; cross-reactivity depends on side chain, and cephalexin shares an identical side chain with ampicillin.

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

Interactions. Metformin (cephalexin raises metformin exposure through renal transporter inhibition), probenecid (raises levels), warfarin (INR rise), oral typhoid vaccine.

Laboratory interference. False-positive urine glucose with copper reduction tests and positive direct Coombs test.

Common prescribing errors. Using it for MRSA or enterococcal infection and for presumed UTI without local susceptibility data, and giving 4 times daily to children when twice daily dosing is used.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: adjust by kidney function. - Kidney impairment: creatinine clearance over 50 mL/min no change; 10 to 50 mL/min 250 to 500 mg every 8 to 12 hours; under 10 mL/min 250 mg every 12 to 24 hours. Haemodialysis: give after dialysis. - Liver impairment: no adjustment. - Region: widely available; local E. coli resistance is high in many East African urinary isolates, so check susceptibility.

Administration. Capsules, tablets and suspension; with or without food (food reduces nausea). Shake suspension and measure with a syringe.

Baseline and monitoring. - Baseline: allergy history; creatinine if risk of kidney disease. - During treatment: review at 48 to 72 hours; full blood count and creatinine in courses over 14 days. - No therapeutic drug monitoring.

Stop rules. Stop for urticaria, angioedema, mucosal skin reaction or persistent diarrhoea with fever.

Referral and escalation. Refer for spreading cellulitis, systemic features, abscess needing drainage and failure at 48 to 72 hours.