What is the maximum recommended dose of amoxicillin for a patient with normal renal function and no history of allergic reactions to penicillins?

Maximum Amoxicillin Dosing for Patients with Normal Renal Function

For adults with normal renal function and no penicillin allergy, the maximum recommended dose of amoxicillin is 500 mg three times daily (1500 mg/day total) for typical outpatient infections like cellulitis, or up to 200 mg/kg/day (divided into 4-6 doses) intravenously for severe infections such as infective endocarditis. 1

Standard Adult Dosing by Indication

Uncomplicated Skin and Soft Tissue Infections (Cellulitis)

• For typical nonpurulent cellulitis, amoxicillin 500 mg orally three times daily for 5 days is the standard regimen, extending only if clinical improvement has not occurred within this timeframe 2, 3
• Beta-lactam monotherapy with amoxicillin alone is successful in 96% of cellulitis cases, as MRSA is an uncommon cause even in high-prevalence settings 3
• The 500 mg three times daily dosing provides adequate streptococcal coverage, which is the primary pathogen in most cellulitis cases 3

Severe Infections Requiring IV Therapy

• For infective endocarditis caused by penicillin-susceptible streptococci, adults should receive 100-200 mg/kg/day IV divided into 4-6 doses for 4 weeks 1
• For penicillin-resistant streptococci (MIC 0.25-2 mg/L), the dose increases to 200 mg/kg/day IV in 4-6 doses for 4 weeks 1
• In the context of enterococcal endocarditis, ampicillin (closely related to amoxicillin) is dosed at 12 g per 24 hours IV in 6 equally divided doses for 4-6 weeks 2

Pediatric Maximum Dosing

Standard Pediatric Dosing

• For children with Lyme disease (erythema migrans), the maximum dose is 50 mg/kg per day in 3 divided doses with a maximum of 500 mg per dose 2
• For streptococcal pharyngitis, children receive either 50 mg/kg once daily (maximum 1,000 mg) or 25 mg/kg twice daily (maximum 500 mg) for 10 days 1

High-Dose Pediatric Regimens for Resistant Organisms

• For pneumococcal infections with intermediate penicillin resistance, high-dose amoxicillin at 80-90 mg/kg/day is recommended 4, 5
• Monte Carlo simulations demonstrate that high-dose amoxicillin (45 mg/kg/dose every 12 hours, totaling 90 mg/kg/day) achieves >93% probability of target attainment in serum for pneumococcal pneumonia 6
• Standard-dose amoxicillin (15 mg/kg/dose every 8 hours, totaling 45 mg/kg/day) achieves only >71% probability of target attainment, making high-dose regimens preferable for resistant organisms 6

Pediatric Infective Endocarditis

• For penicillin-susceptible streptococcal endocarditis in children, the dose is 300 mg/kg/day IV in 4-6 equally divided doses for standard 4-week treatment 1

Critical Dosing Considerations

Weight-Based Dosing Disparities in Children

• A significant dosing disparity exists in pediatric practice: smaller children receive doses approaching 80-90 mg/kg/day, while larger children often receive declining doses per kilogram 4
• Most children above 60 kg are dosed at less than 40 mg/kg/day, which may be subtherapeutic for infections requiring high-dose amoxicillin 4
• Children are reaching the adult maximum dose (1500 mg/day) at weights as low as 15-20 kg, potentially resulting in underdosing for larger children with resistant organisms 4

Pharmacokinetic Optimization

• For children with pneumonia, amoxicillin 25 mg/kg/dose twice daily (50 mg/kg/day total) provides superior pharmacokinetics compared to 15 mg/kg/dose three times daily (45 mg/kg/day total), with mean AUC of 54.7 vs 24.9 μg·h/mL after the first dose 7
• To lengthen time above MIC at higher concentration levels, doses of 30-40 mg/kg twice daily should be considered instead of 25 mg/kg/dose 7

Common Pitfalls to Avoid

• Do not reflexively cap pediatric doses at "adult maximum" (1500 mg/day) for larger children with infections requiring high-dose therapy—this results in subtherapeutic dosing for resistant organisms 4
• Do not use amoxicillin alone for cellulitis with MRSA risk factors (penetrating trauma, purulent drainage, injection drug use)—these require MRSA-active antibiotics 3
• Do not extend treatment beyond 5 days for uncomplicated cellulitis based solely on residual erythema—some inflammation persists even after bacterial eradication 3
• Do not combine amoxicillin with MRSA-active agents for typical nonpurulent cellulitis—this represents overtreatment without improving outcomes 3

Renal Dosing Adjustments

• The evidence provided does not specify maximum doses for patients with renal impairment, but standard practice requires dose reduction when creatinine clearance falls below 30 mL/min
• For patients with GFR 30-70 mL/min, standard dosing intervals should be extended (e.g., from every 8 hours to every 12 hours)