Amoxicillin

Amoxicillin is an aminopenicillin with good oral absorption and wider Gram-negative and enterococcal activity than natural penicillins. It is the first-line oral antibiotic for community-acquired respiratory infection in children and adults and for many ear, throat and sinus infections.

Classification. Beta-lactam, aminopenicillin. Susceptible to beta-lactamases; combined with clavulanic acid when resistance is likely.

Mechanism. Blocks penicillin-binding proteins; time-dependent killing, so dosing frequency and time over MIC matter.

Spectrum. Streptococci, pneumococci (including intermediate resistance at high dose), Enterococcus faecalis, Listeria monocytogenes, non-beta-lactamase Haemophilus influenzae, Neisseria meningitidis, Helicobacter pylori and some Escherichia coli, Proteus mirabilis and Salmonella. Not active against staphylococci that produce penicillinase, Klebsiella, Pseudomonas or most Moraxella.

Pharmacokinetics. Oral bioavailability about 70 to 90%, unaffected by food. Half-life 1 to 1.5 hours. Mainly renal elimination; about 60% excreted unchanged in 6 hours. Dose accumulation occurs in renal failure. Crosses the placenta and reaches breast milk in small amounts.

No loading dose. Titration is by severity, site and organism MIC. Maximum oral dose is 3 g daily for most adults (4 g in selected high-dose regimens). Maximum IV dose 12 g daily.

Community-acquired pneumonia, mild, adults. 500 mg to 1 g every 8 hours for 5 days (extend to 7 days if slow response). Children 3 months to 12 years: 40 mg/kg every 12 hours or 25 mg/kg every 8 hours, maximum 1 g a dose, for 3 to 5 days.

Acute otitis media. Children: 40 mg/kg every 12 hours (80 to 90 mg/kg/day), 5 days over age 2 and 10 days under 2 or in severe disease. Adults 500 mg to 1 g every 8 hours for 5 days.

Acute bacterial sinusitis. Adults 500 mg to 1 g every 8 hours for 5 to 7 days.

Streptococcal pharyngitis. Adults 500 mg every 12 hours or 1 g once daily for 10 days; children 50 mg/kg once daily (maximum 1 g) for 10 days.

Helicobacter pylori. 1 g every 12 hours for 14 days in triple and bismuth regimens; 1 g every 8 hours for 14 days in high-dose dual regimens; always with acid suppression.

Uncomplicated urinary tract infection. 500 mg every 8 hours for 5 to 7 days only if the isolate is susceptible; resistance of Escherichia coli is high in many settings.

Early Lyme disease. 500 mg every 8 hours for 14 days (up to 21).

Severe acute malnutrition, uncomplicated. 15 mg/kg every 8 hours for 5 days; local practice varies.

Intravenous (where available). 1 g every 8 hours for moderate infection; 2 g every 4 to 6 hours for Listeria meningitis, enterococcal endocarditis and severe sepsis, maximum 12 g daily.

Endocarditis prophylaxis. 2 g single dose 30 to 60 minutes before the procedure in high-risk dental procedures; many services now omit it.

Neonates. 30 mg/kg every 12 hours orally in the first week; seek paediatric advice for IV doses.

Contraindications. Penicillin hypersensitivity.

Adverse effects. Diarrhoea, nausea, maculopapular rash, candidiasis, Clostridioides difficile infection. Serious: anaphylaxis, interstitial nephritis, crystalluria at high dose with dehydration, cholestatic hepatitis (rare, more with clavulanate), cytopenias, and toxic epidermal necrolysis (rare). A non-allergic rash occurs in most patients with infectious mononucleosis, CMV or lymphoproliferative disease; avoid use there.

Interactions. Methotrexate (raises toxicity), warfarin and acenocoumarol (INR rise), allopurinol (more rash), probenecid (raises levels), oral typhoid vaccine (live). No proven effect on oral contraceptive efficacy.

Common prescribing errors. Under-dosing pneumococcal infection, using it for presumed UTI without susceptibility, giving 3-times-daily doses to children when twice-daily dosing is the supplied schedule, and no dose adjustment in renal failure.

Special groups.

• Pregnancy: safe; breastfeeding: safe, watch infant stool and thrush.
• Children: dose by weight; dispersible 250 mg tablets are widely supplied in East Africa.
• Older adults: reduce dose if creatinine clearance falls.
• Kidney impairment: creatinine clearance over 30 mL/min no change; 10 to 30 mL/min maximum 500 mg every 12 hours (IV: usual dose every 12 hours); under 10 mL/min 500 mg every 24 hours; haemodialysis 500 mg every 24 hours with an extra dose after dialysis.
• Liver impairment: caution, no fixed reduction; monitor liver tests in prolonged courses.
• Obesity: use actual dose; do not exceed the maximum.

Formulations. Capsules 250 mg and 500 mg; dispersible tablets 250 mg; suspension 125 mg and 250 mg in 5 mL; IV vials where licensed (500 mg, 1 g, 2 g).

Administration. Take with or without food; with food reduces nausea. IV: reconstitute in water for injection, give by slow injection over 3 to 4 minutes or infuse in 0.9% sodium chloride over 30 to 60 minutes; discard unused solution after the labelled period.

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

Stop rules. Stop for urticaria with angioedema, severe rash with mucosal involvement, hepatic injury, or persistent diarrhoea with fever.

Referral and escalation. Refer for treatment failure at 48 to 72 hours, suspected complications such as empyema or mastoiditis, and Listeria or enterococcal endocarditis.