What is the recommended dosage and treatment duration for Amoxicillin (amoxicillin) in adults with bacterial infections?

Amoxicillin Dosing for Adult Bacterial Infections

For adults with mild community-acquired bacterial infections without recent antibiotic use, amoxicillin 500 mg three times daily (1.5 g/day total) is appropriate, while moderate infections or those with risk factors for resistance require high-dose amoxicillin 1 g three times daily (3-4 g/day total). 1, 2

Standard Dosing Regimens

Mild Infections (No Recent Antibiotic Use)

• Amoxicillin 500 mg orally three times daily for patients with mild community-acquired respiratory tract infections who have not received antibiotics in the past 4-6 weeks 1
• Total daily dose: 1.5 g/day divided every 8 hours 1, 2
• This lower dose is appropriate when there are no risk factors for drug-resistant Streptococcus pneumoniae (DRSP) 1

High-Dose Regimens for Moderate Disease or Resistance Risk

• Amoxicillin 1 g orally three times daily (3-4 g/day total) for patients with moderate disease, recent antibiotic exposure, or high local prevalence of penicillin-resistant S. pneumoniae 1, 2
• High-dose therapy (4 g/day) is specifically indicated for areas with high DRSP prevalence, patients requiring better Haemophilus influenzae coverage, or those with risk factors for resistant pathogens 1
• The FDA-approved dosing range for adults is 750-1750 mg/day in divided doses every 8-12 hours 2

Infection-Specific Dosing

Acute Bacterial Rhinosinusitis

• Mild disease without recent antibiotic use: Amoxicillin 1.5-4 g/day divided every 8 hours 1
• Moderate disease or recent antibiotic use: Amoxicillin 4 g/day (1 g every 6 hours or approximately 1.3 g every 8 hours) 1
• Calculated clinical efficacy: 87-88% for standard dosing 1

Community-Acquired Pneumonia

• Outpatients without cardiopulmonary disease: Macrolide preferred, but amoxicillin can be used 1
• Outpatients with cardiopulmonary disease or modifying factors: High-dose amoxicillin 1 g every 8 hours PLUS a macrolide or doxycycline to cover atypical pathogens 1
• The combination is necessary because amoxicillin alone does not cover Mycoplasma pneumoniae or Chlamydia pneumoniae 1

Helicobacter pylori Infection

• Triple therapy: Amoxicillin 1 g twice daily (every 12 hours) combined with clarithromycin 500 mg and lansoprazole 30 mg for 14 days 2
• Dual therapy: Amoxicillin 1 g three times daily (every 8 hours) with lansoprazole 30 mg for 14 days 2

Treatment Duration

Respiratory Tract Infections

• Acute bacterial rhinosinusitis: 10 days for adults (though some guidelines suggest 5-7 days may be sufficient) 1, 3, 4
• Community-acquired pneumonia: 7-15 days depending on severity and clinical response 5
• Lower respiratory tract infections: 7-15 days 5

Other Infections

• Skin and skin structure infections: 7-10 days 2
• Genitourinary tract infections: 3-7 days for uncomplicated UTIs 3
• Upper respiratory tract infections: 7-10 days 3

Critical Dosing Considerations

When to Use High-Dose Therapy

High-dose amoxicillin (3-4 g/day) should be used when: 1, 3

• Recent antimicrobial use within 4-6 weeks
• Frequent exposure to children in daycare settings
• Immunodeficiency or immunocompromised status
• Age >65 years
• Geographic areas with high prevalence of penicillin-resistant S. pneumoniae (MIC >2 mg/L)
• Moderate to severe infection (e.g., frontal or sphenoidal sinusitis)
• Prior antibiotic therapy failure

Renal Dose Adjustment

• Reduce dose in patients with severe renal impairment (GFR <30 mL/min) 2
• The FDA label recommends dosage reduction but does not specify exact adjustments; clinical judgment and monitoring are required 2

Clinical Response Assessment

• Evaluate clinical response within 48-72 hours of initiating therapy 3
• Lack of improvement after 72 hours should prompt either a switch to alternative antimicrobial therapy or patient reevaluation 1
• For sinusitis, fever should resolve within 24 hours for pneumococcal infections, though 2-4 days may be necessary for other etiologies 1

Common Pitfalls and Caveats

Amoxicillin vs. Amoxicillin-Clavulanate

• Plain amoxicillin does NOT cover β-lactamase-producing organisms such as many strains of H. influenzae and Moraxella catarrhalis 1, 6
• If β-lactamase-producing organisms are suspected, amoxicillin-clavulanate should be used instead 1, 6
• For amoxicillin-clavulanate, the high-dose regimen is 4 g amoxicillin/250 mg clavulanate per day (not 4 g/500 mg) to avoid excessive clavulanate-related diarrhea 1, 4

Resistance Considerations

• Amoxicillin achieves peak serum levels of approximately 6.75 mcg/mL after 500 mg and 9.90 mcg/mL after 1 g 7
• The pharmacodynamic target is 40% time above MIC (40%T>MIC) 8
• For bacterial MICs of 8 mg/L, only 65% of hospitalized patients reached the 40%T>MIC target with standard dosing 8
• This underscores the importance of high-dose therapy when resistance is suspected 8

Coverage Gaps

• Amoxicillin does not cover atypical pathogens (Mycoplasma, Chlamydia, Legionella), so combination therapy with a macrolide or doxycycline is required for community-acquired pneumonia in patients with cardiopulmonary disease 1
• Amoxicillin has limited activity against penicillin-resistant S. pneumoniae at standard doses 1, 6

Twice-Daily Dosing

• Amoxicillin-clavulanate 875/125 mg twice daily is as effective as 500/125 mg three times daily for lower respiratory tract infections and may improve compliance 5
• However, for plain amoxicillin, three-times-daily dosing is generally preferred to maintain adequate time above MIC 1, 2