What are the recommended adult and pediatric dosing, duration, contraindications, and alternatives for Augmentin (amoxicillin‑clavulanate) in common community‑acquired infections?

Augmentin (Amoxicillin-Clavulanate) Dosing and Clinical Use

Adult Dosing by Indication

Respiratory Tract Infections

For acute bacterial rhinosinusitis:

• Standard dose: 875 mg/125 mg twice daily for 5–7 days is the preferred first-line regimen, achieving 90–92% predicted clinical efficacy 1
• High-dose regimen: 2000 mg/125 mg twice daily for patients with recent antibiotic use (past 4–6 weeks), age >65 years, moderate-to-severe symptoms, comorbidities, immunocompromised status, or regional penicillin-resistant S. pneumoniae prevalence >10% 1
• Duration: 5–7 days is as effective as 10 days and results in fewer adverse effects 1

For community-acquired pneumonia (outpatient with comorbidities):

• Mandatory combination therapy: 875 mg/125 mg twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5–7 days total 2
• Never use Augmentin as monotherapy for pneumonia—it lacks atypical pathogen coverage (Mycoplasma, Chlamydophila, Legionella), which account for 10–40% of cases 2
• Alternative high-dose: 2000 mg/125 mg twice daily plus azithromycin when penicillin-resistant S. pneumoniae MIC ≤4 mg/L is suspected 2

For acute exacerbations of chronic bronchitis:

• High-dose short course: 2000 mg/125 mg twice daily for 5 days is as effective as 875 mg/125 mg twice daily for 7 days, with 93% clinical success 3

Skin and Soft Tissue Infections

• Animal or human bites: 875 mg/125 mg twice daily for 7–10 days 4
• Standard infections: 875 mg/125 mg twice daily for 7–10 days 4

Intravenous Dosing (Severe Infections)

• Complicated intra-abdominal infections, severe pneumonia, severe skin/soft tissue infections: 1.2 g IV every 8 hours 4
• Duration: 4–7 days with adequate source control for intra-abdominal infections 4

---

Pediatric Dosing

Standard-Dose Regimen

• 45 mg/kg/day of amoxicillin component with 6.4 mg/kg/day clavulanate, divided into 2 doses for uncomplicated infections 1

High-Dose Regimen (Strongly Recommended First-Line)

• 80–90 mg/kg/day of amoxicillin component with 6.4 mg/kg/day clavulanate, divided into 2 doses for 10–14 days 1
• Indications for high-dose: Age <2 years, daycare attendance, recent antibiotic use (past 4–6 weeks), incomplete Hib vaccination, regional penicillin-resistant *S. pneumoniae* >10%, moderate-to-severe illness, concurrent purulent otitis media, or pneumonia not responding to amoxicillin alone 1
• Maximum daily dose: 4000 mg amoxicillin 1

Acute Otitis Media

• High-dose formulation (Augmentin ES-600): 90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate in 2 divided doses for persistent or recurrent AOM with risk factors for resistant pathogens 5
• The 14:1 ratio (amoxicillin:clavulanate) in high-dose formulations causes less diarrhea than conventional formulations 1

---

Treatment Duration by Condition

• Acute bacterial rhinosinusitis (adults): 5–7 days 1
• Acute bacterial rhinosinusitis (children): 10–14 days 1
• Community-acquired pneumonia: Minimum 5 days AND until afebrile 48–72 hours with ≤1 sign of clinical instability; typical duration 5–7 days 2
• Extended therapy (14–21 days): Only for Legionella pneumophila, Staphylococcus aureus, or gram-negative enteric bacilli 2
• Skin/soft tissue infections: 7–10 days 4
• Intra-abdominal infections: 4–7 days with source control 4

---

Contraindications and Precautions

Absolute Contraindications

• History of cholestatic jaundice or hepatic dysfunction associated with prior amoxicillin-clavulanate use 6
• Severe immediate hypersensitivity (anaphylaxis, Stevens-Johnson syndrome) to any penicillin 6

Relative Contraindications and Cautions

• Infectious mononucleosis: High risk of maculopapular rash with amoxicillin 6
• **Renal impairment (CrCl <30 mL/min):** Reduce dosing frequency; no adjustment needed for CrCl >30 mL/min with 875 mg/125 mg formulation 2
• Hepatic impairment: Monitor liver function; clavulanate is hepatically metabolized 6

---

Critical Prescribing Pitfalls to Avoid

1. Never substitute tablet strengths incorrectly: Two 250 mg/125 mg tablets ≠ one 500 mg/125 mg tablet due to excessive clavulanate causing increased GI side effects 4

2. Never use Augmentin as monotherapy for pneumonia: Always combine with a macrolide (azithromycin or clarithromycin) to cover atypical pathogens 2

3. Avoid macrolide combination in regions with >25% pneumococcal macrolide resistance without considering respiratory fluoroquinolones 2

4. Do not use for simple streptococcal pharyngitis: Penicillin V or plain amoxicillin are first-line; reserve Augmentin for chronic streptococcal carriers with recurrent symptomatic episodes 4

5. Recent antibiotic exposure (<90 days): Select an agent from a different class to reduce resistance risk 2

6. Do not extend therapy beyond 7–8 days in clinically improving patients without specific indication (Legionella, S. aureus, gram-negative bacilli) 2

---

Alternatives When Augmentin Is Contraindicated

For Respiratory Infections

• Penicillin allergy (non-severe): Cefuroxime or cefpodoxime plus azithromycin 2
• Severe penicillin allergy: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) 2
• Macrolide allergy: Doxycycline 100 mg twice daily (for healthy adults without comorbidities) 2

For Skin/Soft Tissue Infections

• Penicillin allergy: Clindamycin 300–450 mg three times daily 4

For Intra-Abdominal Infections (Mild-to-Moderate)

• Alternatives: Ertapenem, moxifloxacin, tigecycline, or cefazolin/cefuroxime/ceftriaxone plus metronidazole 7

---

Clinical Reassessment Criteria

Adults

• At 3–5 days: If no clinical improvement, switch to high-dose Augmentin or respiratory fluoroquinolone 1
• At 7 days: Persistent or worsening symptoms require diagnostic reconsideration, imaging, and ENT referral 1

Children

• At 72 hours: Lack of improvement or worsening warrants escalation to high-dose Augmentin 1

Pneumonia (All Ages)

• At 48–72 hours: Fever should resolve; if not, reassess for complications, resistant organisms, or alternative diagnoses 2

---

Pharmacokinetic Advantages of High-Dose Formulations

• Augmentin XR (2000 mg/125 mg twice daily): Maintains plasma amoxicillin concentrations >4 µg/mL for 49% of the dosing interval, providing superior activity against penicillin-resistant S. pneumoniae with MICs up to 4 µg/mL 6
• Augmentin ES-600 (90 mg/kg/day pediatric): Achieves high middle ear fluid concentrations to eradicate penicillin-resistant S. pneumoniae (MIC ≤2 µg/mL) 5

---

Tolerability and Adverse Effects

• Most common: Mild gastrointestinal disturbances (diarrhea, nausea) 5
• Twice-daily dosing causes significantly less severe diarrhea (1% vs 2%, p<0.05) than three-times-daily dosing due to reduced daily clavulanate exposure 4, 8
• High-dose formulations (14:1 ratio): Similar tolerability to conventional formulations 5
• Serious adverse events: Rare; large postmarketing study reported 3.6% total adverse event incidence in children 5