Can amoxicillin be dosed once daily for infections, including urinary tract infections (UTIs)?

Once-Daily Amoxicillin Dosing

Once-daily amoxicillin dosing can be used appropriately for specific infections, particularly Group A Streptococcal (GAS) pharyngitis in children, but is not recommended for urinary tract infections where standard twice or three-times daily dosing remains the evidence-based approach.

Appropriate Once-Daily Use

Group A Streptococcal Pharyngitis

• Once-daily amoxicillin at 50 mg/kg/day is an acceptable alternative to standard three-times-daily dosing for GAS pharyngitis in pediatric patients 1
• This represents the primary clinical scenario where once-daily amoxicillin has guideline support 1
• The total daily dose remains the same (50 mg/kg/day), just administered as a single dose rather than divided 1

Inappropriate Once-Daily Use

Urinary Tract Infections

• For UTIs, amoxicillin should be dosed 500 mg every 8 hours (three times daily) for 7 days in uncomplicated cases 2
• Alternative regimens include 875 mg every 12 hours (twice daily) for more severe infections 2
• The Infectious Diseases Society of America specifically recommends these divided dosing schedules to maintain adequate urinary concentrations 2
• Single-dose amoxicillin (3 g) has been studied but showed inferior cure rates (60.6%) compared to standard therapy (73.6%) 3

Skin and Soft Tissue Infections

• Standard dosing for impetigo and other SSTIs requires 25 mg/kg/day divided into 2-4 doses, not once daily 1
• The amoxicillin/clavulanate formulation specifically uses 875/125 mg twice daily, not once daily 1

Pharmacokinetic Rationale

Why Once-Daily Works for Some Infections

• GAS pharyngitis responds to once-daily dosing because the total daily exposure (AUC) is sufficient for this highly susceptible organism 1
• The concentration at the pharyngeal site remains adequate throughout the 24-hour period 1

Why Once-Daily Fails for UTIs

• Urinary pathogens require sustained urinary concentrations above the MIC throughout the dosing interval 2
• Three-times-daily dosing (250 mg TID or 500 mg TID) maintains these concentrations more reliably 4
• Even twice-daily formulations required increased amoxicillin content (875 mg) to maintain efficacy 5

Common Pitfalls to Avoid

• Do not extrapolate once-daily pediatric GAS pharyngitis dosing to adult infections or other infection types 1
• Avoid underdosing by attempting once-daily regimens for UTIs—this leads to treatment failure and resistance 2
• Do not confuse amoxicillin with amoxicillin/clavulanate dosing schedules—the combination product is specifically formulated for twice-daily use 6, 5
• Never use once-daily dosing for complicated infections, pyelonephritis, or infections requiring tissue penetration 2

Clinical Decision Algorithm

For GAS pharyngitis in children:

• Use 50 mg/kg once daily as an alternative to divided dosing 1

For uncomplicated UTI:

• Use 500 mg three times daily for 7 days 2
• Alternative: 875 mg twice daily for more severe cases 2

For all other infections:

• Follow standard divided dosing schedules (2-4 times daily depending on indication) 1, 2
• Consider amoxicillin/clavulanate 875/125 mg twice daily for broader coverage 6