Cefaclor

Cefaclor is an oral second-generation cephalosporin with modest Haemophilus influenzae activity. It is now a second-line option because of weaker pneumococcal activity and a higher rate of serum sickness-like reactions than other oral beta-lactams.

Classification. Beta-lactam, second-generation cephalosporin.

Mechanism. Blocks penicillin-binding proteins and cell wall synthesis.

Spectrum. MSSA, streptococci, some beta-lactamase negative Haemophilus influenzae, Moraxella, and some Escherichia coli, Klebsiella and Proteus. Poor activity against penicillin-nonsusceptible pneumococci, MRSA, Enterococcus, Pseudomonas, anaerobes and ESBL producers.

Pharmacokinetics. Oral bioavailability about 90% for the immediate-release form. Half-life about 0.5 to 1 hour. Mainly renal elimination. The modified-release tablet must be taken with food.

No loading dose. Maximum 4 g daily in adults for immediate-release capsules (usual 750 mg to 1.5 g).

Adults. - Immediate release: 250 to 500 mg every 8 hours for 5 to 10 days. - Modified release: 375 to 500 mg every 12 hours with food. - Indications: pharyngitis, otitis media, sinusitis, bronchitis and uncomplicated skin and urinary infection when susceptibility is likely.

Children. 20 mg/kg/day divided every 8 hours (or every 12 hours for pharyngitis and mild infection); 40 mg/kg/day for otitis media and severe infection; maximum 1 g daily.

Alternatives. Amoxicillin, amoxicillin clavulanate, cefuroxime, cefpodoxime, cefixime, azithromycin.

Contraindications. Cephalosporin hypersensitivity; previous serum sickness-like reaction to cefaclor.

Serum sickness-like reaction. Urticaria or erythema multiforme with arthralgia, fever and lymphadenopathy 5 to 14 days after starting, most often in children and with repeat courses; the frequency is higher than with other beta-lactams. Stop the drug and treat symptomatically.

Other adverse effects. Diarrhoea, nausea, candidiasis, Clostridioides difficile infection, anaphylaxis, haemolytic anaemia, cholestatic hepatitis, interstitial nephritis, seizures in renal failure.

Interactions. Warfarin (INR rise), probenecid, aluminium and magnesium antacids (reduce modified-release absorption), live oral typhoid vaccine.

Common prescribing errors. Using it for pneumococcal pneumonia, repeated courses in children and giving modified-release tablets without food.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: adjust by kidney function. - Kidney impairment: creatinine clearance over 10 mL/min no change; under 10 mL/min halve the dose. Haemodialysis: give after the session. - Liver impairment: no adjustment. - Region: limited availability in East Africa.

Formulations. Capsules, tablets (modified release) and suspension. Shake suspension and measure with a syringe.

Baseline and monitoring. - Baseline: allergy history including prior cefaclor reaction, creatinine. - During treatment: review at 48 to 72 hours; look for joint pain, rash and fever from day 5 onwards. - No therapeutic drug monitoring.

Stop rules. Stop for urticaria with arthralgia, mucosal skin reaction or anaphylaxis.

Referral and escalation. Refer for failure to improve at 48 to 72 hours and for a suspected serum sickness-like reaction with organ involvement.