What is the recommended dosing for Augmentin (amoxicillin-clavulanate) in a patient with a positive E. coli infection and potentially impaired renal function?

Augmentin Dosing for E. coli Infections

Standard Dosing for Adults with Normal Renal Function

For E. coli infections in adults with normal renal function, Augmentin should be dosed at 875 mg/125 mg orally every 12 hours or 500 mg/125 mg every 8 hours, depending on infection severity. 1

• For less severe infections (uncomplicated UTIs, mild soft tissue infections): 500 mg/125 mg every 8 hours or 875 mg/125 mg every 12 hours 1
• For more severe infections (complicated UTIs, lower respiratory tract infections): 875 mg/125 mg every 12 hours is preferred 1
• The every 12-hour regimen is associated with significantly less diarrhea and should be preferred when clinically appropriate 1

Critical Dosing Adjustments for Renal Impairment

Patients with impaired renal function require substantial dose reduction to prevent toxicity, and the 875 mg/125 mg dose is contraindicated in severe renal impairment. 1

Renal Function-Based Dosing Algorithm:

• GFR ≥30 mL/min: No dose adjustment required; use standard dosing 1
• GFR 10-30 mL/min: 500 mg/125 mg or 250 mg/125 mg every 12 hours (depending on severity); do NOT use 875 mg/125 mg dose 1
• GFR <10 mL/min: 500 mg/125 mg or 250 mg/125 mg every 24 hours (depending on severity) 1
• Hemodialysis patients: 500 mg/125 mg or 250 mg/125 mg every 24 hours, with an additional dose both during and at the end of dialysis 1

Important Clinical Caveats

Tablet Formulation Considerations:

Different Augmentin formulations are NOT interchangeable due to varying clavulanate content. 1

• Two 250 mg/125 mg tablets should NOT be substituted for one 500 mg/125 mg tablet (both contain 125 mg clavulanate, resulting in excessive clavulanate with doubled dosing) 1
• The 250 mg/125 mg tablet and 250 mg/62.5 mg chewable tablet are NOT interchangeable 1

Resistance Considerations:

Prior antibiotic exposure, particularly to fluoroquinolones or Augmentin itself, significantly increases the risk of Augmentin-resistant E. coli. 2

• Previous fluoroquinolone exposure increases AMC resistance risk 3.3-fold (OR = 3.33,95% CI = 1.10-10.12) 2
• Previous AMC exposure increases resistance risk 5.7-fold (OR = 5.68,95% CI = 1.97-16.44) 2
• In patients with recent fluoroquinolone or Augmentin exposure within 3 months, consider alternative agents or obtain culture/susceptibility testing before initiating therapy 2

When Augmentin May NOT Be Appropriate:

For severe E. coli infections requiring parenteral therapy or in patients with high resistance risk, alternative agents should be considered. 3

• For complicated intra-abdominal infections with adequate source control: Consider ampicillin/sulbactam 3 g IV every 6-8 hours or piperacillin/tazobactam 3.375-4.5 g IV every 6 hours 3
• For extended-spectrum beta-lactamase (ESBL)-producing E. coli: Augmentin is NOT appropriate; use ertapenem 1 g IV every 24 hours or other carbapenem 3
• For carbapenem-resistant E. coli: Standard beta-lactams including Augmentin are ineffective 4

Duration of Therapy

• Uncomplicated UTI: 5-7 days 1
• Complicated UTI: 5-7 days with adequate source control 3
• Complicated intra-abdominal infections: 4-7 days depending on clinical response and source control 3

Common Pitfalls to Avoid

1. Do NOT use 875 mg/125 mg formulation in patients with GFR <30 mL/min (risk of clavulanate accumulation and hepatotoxicity) 1
2. Do NOT double 250 mg/125 mg tablets to achieve 500 mg amoxicillin dose (results in excessive clavulanate) 1
3. Do NOT assume susceptibility in patients with recent antibiotic exposure; obtain cultures when possible 2
4. Do NOT use empirically for severe sepsis/septic shock from E. coli without culture confirmation, as resistance rates may be high 3, 2