What is amoxicillin?

What is Amoxicillin?

Amoxicillin is a semisynthetic aminopenicillin β-lactam antibiotic with bactericidal activity against Gram-positive and some Gram-negative bacteria, acting by inhibiting bacterial cell wall synthesis and inducing autolysis. 1

Mechanism of Action and Pharmacology

• Amoxicillin inhibits bacterial cell wall biosynthesis during active multiplication, leading to bacterial death through disruption of peptidoglycan synthesis 1
• It is the most active oral β-lactam against streptococci, including pneumococci, due to excellent oral bioavailability 2
• The drug is stable in gastric acid and rapidly absorbed after oral administration, with peak blood levels occurring 1-2 hours post-dose 1
• Approximately 60% is excreted unchanged in urine within 6-8 hours, with a half-life of 61.3 minutes 1
• Amoxicillin is approximately 20% protein-bound and diffuses readily into most body tissues and fluids (except brain and spinal fluid unless meninges are inflamed) 1

Antimicrobial Spectrum

• Gram-positive coverage: Streptococcus pneumoniae, Streptococcus pyogenes, non-hospital Staphylococcus aureus, and enterococci (more active than ampicillin against enterococci) 3, 4
• Gram-negative coverage: Haemophilus influenzae (non-β-lactamase producing), Moraxella catarrhalis (non-β-lactamase producing), Escherichia coli, and Salmonella species 3, 4
• Critical limitation: Amoxicillin is destroyed by β-lactamases produced by both Gram-positive and Gram-negative bacteria 1, 4

Clinical Indications

Respiratory Tract Infections

• First-line agent for community-acquired pneumonia when S. pneumoniae is the suspected pathogen 5
• Acute bacterial sinusitis in patients without risk factors for resistant organisms 5
• Acute otitis media in children without recent antibiotic exposure or daycare attendance 5
• Bacterial exacerbations of bronchitis 4

Other Infections

• Acute lower urinary tract infections 4
• Gonorrhea 4
• Typhoid fever 4
• In specialized settings: oral therapy for endocarditis, septic arthritis, osteomyelitis, and endocarditis prophylaxis 4

Standard Dosing

Adults

• Standard dose: 1.5-1.75 g/day or 3 g/day for respiratory infections 5, 2
• Oral doses of 250-500 mg produce peak levels of 3.5-7.5 mcg/mL 1

Pediatric Patients

• Pneumonia in children <3 years: 80-100 mg/kg/day in three divided doses (for children <30 kg) 5
• Acute bacterial sinusitis (uncomplicated): 45 mg/kg/day in 2 divided doses for children ≥2 years without risk factors 5
• High-dose regimen: 80-90 mg/kg/day in 2 divided doses (maximum 2 g/dose) for children with risk factors or in communities with >10% penicillin-nonsusceptible S. pneumoniae 5
• Dosing should be modified in neonates and infants ≤12 weeks due to incompletely developed renal function 1

Resistance Considerations

• Resistance in S. pneumoniae is relative and can be overcome with higher doses 2
• 10-15% of upper respiratory S. pneumoniae isolates nationally are penicillin-nonsusceptible (up to 50-60% in some areas) 5
• 10-42% of H. influenzae and nearly 100% of M. catarrhalis produce β-lactamases, rendering them resistant to amoxicillin alone 5
• Risk factors for resistance: daycare attendance, antibiotic use within 30 days, age <2 years 5

Amoxicillin-Clavulanate Combination

• Clavulanic acid is a potent β-lactamase inhibitor that preserves amoxicillin activity against β-lactamase-producing bacteria 2, 6
• This combination maintains full activity against S. pneumoniae while achieving 95-100% effectiveness against H. influenzae and 100% against M. catarrhalis 2
• High-dose formulation: 90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate (pediatric) or 4 g amoxicillin with 250 mg clavulanate daily (adult) 5, 2
• The clavulanate component limits maximum daily amoxicillin dosing due to gastrointestinal adverse effects 2

Important Clinical Pearls

• Amoxicillin has superior oral absorption compared to ampicillin, achieving blood levels 2-2.5 times higher 4
• When costs are comparable, amoxicillin should replace ampicillin as the oral aminopenicillin of first choice 4
• Renal dose adjustment required for severe renal impairment (GFR <30 mL/min) 1
• Probenecid delays amoxicillin excretion by competing for renal tubular secretion 1
• Overdosage can cause crystalluria and interstitial nephritis; amoxicillin is removable by hemodialysis 1