What is the recommended dose of amoxicillin-clavulanate (Augmentin) for adults and children with impaired renal function or a history of allergy to penicillin?

Amoxicillin-Clavulanate Dosing

For adults with normal renal function, the standard dose is 875 mg/125 mg twice daily or 500 mg/125 mg three times daily for most infections, with high-dose regimens (2000 mg/125 mg twice daily) reserved for patients with risk factors for resistant organisms. 1

Standard Adult Dosing

For mild-to-moderate infections, prescribe 500 mg/125 mg every 12 hours or 250 mg/125 mg every 8 hours. 1

For more severe infections and respiratory tract infections, prescribe 875 mg/125 mg every 12 hours or 500 mg/125 mg every 8 hours. 1

• The 875/125 mg twice-daily regimen is as effective as 500/125 mg three times daily for lower respiratory tract infections, with significantly less severe diarrhea (1% vs 2%). 2
• Treatment duration is typically 5-7 days for uncomplicated acute bacterial rhinosinusitis in adults, and 7-10 days for most other respiratory infections. 3, 4

High-Dose Regimen for Resistant Organisms

Use 2000 mg/125 mg twice daily when any of these risk factors are present: 3, 5

• Antibiotic use within the past 4-6 weeks
• Age >65 years
• Recent hospitalization
• Immunocompromised status
• Geographic regions with >10% penicillin-nonsusceptible Streptococcus pneumoniae
• Close contact with daycare facilities
• Smoking or household smoker exposure
• Moderate-to-severe infection (fever ≥39°C, frontal/sphenoidal sinusitis)
• History of recurrent infections
• Comorbidities (diabetes, chronic cardiac/hepatic/renal disease)

The high-dose regimen achieves 90-92% predicted clinical efficacy versus 83-88% for standard dosing when resistant organisms are present. 3, 5

Pediatric Dosing

For neonates and infants <12 weeks: 30 mg/kg/day (amoxicillin component) divided every 12 hours using the 125 mg/5 mL suspension. 1

For children ≥12 weeks with standard infections: 25 mg/kg/day every 12 hours or 20 mg/kg/day every 8 hours (amoxicillin component). 1

For children ≥12 weeks with risk factors or more severe infections: 45 mg/kg/day every 12 hours or 40 mg/kg/day every 8 hours (amoxicillin component). 1

For children with high-risk factors (daycare attendance, recent antibiotic use, areas with >10% penicillin-resistant S. pneumoniae, concurrent conjunctivitis): 80-90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate divided into 2 doses (maximum 4000 mg/day amoxicillin). 3, 6

• The 14:1 ratio formulation (high-dose) causes less diarrhea than older formulations. 3, 6
• The every-12-hour regimen is preferred as it causes significantly less diarrhea than every-8-hour dosing. 1

Renal Impairment Dosing

For patients with severe renal impairment (GFR <30 mL/min), dosage adjustment is required as amoxicillin is primarily eliminated by the kidney. 1

• For GFR <30 mL/min: Reduce frequency to every 24 hours or use 250-500 mg/125 mg every 24 hours depending on infection severity. 1
• Monitor renal function in elderly patients, as they are more likely to have decreased renal function. 1

Penicillin Allergy Alternatives

For patients with penicillin allergy, do NOT use amoxicillin-clavulanate. 7, 5

Alternative antibiotics include: 7, 5

• Adults: Doxycycline or respiratory fluoroquinolones (levofloxacin or moxifloxacin)
• Children with non-Type I hypersensitivity: Clindamycin plus third-generation oral cephalosporin
• Children with Type I hypersensitivity: Avoid all beta-lactams; use macrolides or fluoroquinolones (age-appropriate)

Critical Dosing Caveats

Never substitute two 250 mg/125 mg tablets for one 500 mg/125 mg tablet, as this results in excessive clavulanate dosing (250 mg vs 125 mg). 1

The 250 mg/125 mg tablet and 250 mg/62.5 mg chewable tablet are NOT interchangeable due to different clavulanate content. 1

Take at the start of meals to enhance clavulanate absorption and minimize gastrointestinal intolerance. 1

Avoid macrolides and trimethoprim-sulfamethoxazole for respiratory infections due to high resistance rates (>40% for macrolides, 50% for TMP-SMX against S. pneumoniae). 5

Treatment Duration by Indication

• Acute bacterial rhinosinusitis (adults): 5-7 days 3, 4
• Acute bacterial rhinosinusitis (children): 10-14 days 3
• Acute otitis media: 10 days 1
• Community-acquired pneumonia: 5-7 days if afebrile for 48 hours and clinically stable 4
• Skin/soft tissue infections: 7-10 days 4
• Animal/human bites: 7-10 days 4

Reassess patients who fail to improve after 72 hours and consider changing antibiotics, obtaining cultures, or imaging. 3