Augmentin (Amoxicillin-Clavulanate): Comprehensive Clinical Guide
Primary Indications
Augmentin is first-line therapy for acute otitis media, acute bacterial rhinosinusitis, and community-acquired pneumonia when β-lactamase-producing organisms or penicillin-resistant Streptococcus pneumoniae are suspected. 1
Respiratory Tract Infections
- Acute otitis media (AOM): First-line for children with severe disease, bilateral AOM in ages 6-23 months, or recent antibiotic exposure within 30 days 1
- Acute bacterial rhinosinusitis (ABRS): Preferred over amoxicillin alone in both adults (weak recommendation) and children (strong recommendation) 2
- Community-acquired pneumonia: Indicated for outpatient children <5 years with presumed bacterial pneumonia 1
- Acute exacerbations of chronic bronchitis: Effective for β-lactamase-producing H. influenzae 2
Other Indications
- Urinary tract infections caused by amoxicillin-resistant organisms 3
- Skin and soft tissue infections, including animal or human bite wounds 2
- Intra-abdominal and pelvic infections with mixed aerobic/anaerobic organisms 4
Dosing Regimens
Pediatric Dosing (≥3 months of age)
High-dose amoxicillin-clavulanate (90 mg/kg/day amoxicillin + 6.4 mg/kg/day clavulanate in 2 divided doses) is the standard pediatric regimen for respiratory infections. 1
Age-Based Oral Dosing
- 1-12 months: 2.5 mL of 125/31 suspension three times daily 1
- 1-6 years: 5 mL of 125/31 suspension three times daily 1
- 7-12 years: 5 mL of 250/62 suspension three times daily 1
- 12-18 years: 1 tablet (250/125) three times daily 1
Weight-Based High-Dose Regimen
- Standard dose: 45 mg/kg/day amoxicillin component divided into 2-3 doses 1
- High-dose: 90 mg/kg/day amoxicillin + 6.4 mg/kg/day clavulanate divided into 2 doses (maximum 4000 mg/day amoxicillin) 1
- Maximum single dose: 2 grams per dose regardless of weight 1
Indications for High-Dose Pediatric Therapy
Use 90 mg/kg/day when ANY of the following risk factors are present:
- Age <2 years 1
- Daycare attendance 1, 2
- Recent antibiotic use within 30 days 1
- Incomplete Haemophilus influenzae type b vaccination 1
- Geographic area with >10% penicillin-resistant S. pneumoniae 1
- Moderate to severe illness 1
- Concurrent purulent otitis media 1
- Bilateral AOM in children 6-23 months 1
Intravenous Pediatric Dosing
- All ages: 30 mg/kg three times daily IV 1
Adult Dosing
For uncomplicated respiratory infections, use 875 mg/125 mg twice daily for 5-7 days; for high-risk patients, use 2000 mg/125 mg (Augmentin XR) twice daily. 2
Standard Adult Regimens
- Mild to moderate infections: 500 mg/125 mg every 8 hours OR 875 mg/125 mg every 12 hours 2
- Respiratory infections (standard): 625 mg (500/125) three times daily for 7-10 days 2
- Acute bacterial sinusitis: 875 mg/125 mg twice daily for 5-7 days 2
High-Dose Adult Regimen (Augmentin XR)
Intravenous Adult Dosing
- Severe pneumonia: 1.2 g three times daily IV 2
Treatment Duration
Pediatric Duration
- Acute otitis media: 10 days for children <6 years; 8-10 days for children <2 years 1
- Acute bacterial rhinosinusitis: 10-14 days 1, 2
- Community-acquired pneumonia: 10 days 1
- General guideline: Continue for 7 days after symptom resolution 1
Adult Duration
- Acute bacterial rhinosinusitis: 5-7 days (as effective as 10-day courses) 2, 5
- Respiratory infections: 7-10 days 2
- Bronchiectasis exacerbations: 14 days 2
- General guideline: Continue for 7 days after symptom resolution 2
Contraindications
Absolute Contraindications
- History of serious hypersensitivity (anaphylaxis, Stevens-Johnson syndrome) to amoxicillin, clavulanate, or any β-lactam antibiotic 6
- History of cholestatic jaundice or hepatic dysfunction associated with prior amoxicillin-clavulanate use 4
Relative Contraindications
- Infectious mononucleosis: High risk of maculopapular rash 4
- Severe renal impairment: Requires dose adjustment; prolonging dosing interval according to creatinine clearance is essential 1
Adverse Effects
Common Adverse Effects (Occur Frequently)
Diarrhea is the most common adverse effect, occurring in 25-44% of patients on high-dose regimens versus 14-15% with placebo. 6
- Gastrointestinal: Diarrhea (most common), nausea, vomiting, abdominal pain 6, 4
- Dermatologic: Rash, diaper dermatitis (51% vs 35% placebo in children) 1
- Overall adverse event rate: 44% with high-dose amoxicillin-clavulanate vs 14% with placebo in sinusitis trials 6
The 14:1 ratio formulation (90/6.4 mg/kg/day) causes less diarrhea than other amoxicillin-clavulanate preparations while maintaining efficacy. 1
Serious Adverse Effects (Rare but Life-Threatening)
- Anaphylaxis 6
- Stevens-Johnson syndrome 6
- Cholestatic hepatitis 4
- Clostridioides difficile colitis (risk increased with recent antibiotic exposure) 6
Long-Term Risks in Children
- Disruption of intestinal microbiome contributing to inflammatory bowel disease, obesity, eczema, and asthma 6
- Antimicrobial resistance at individual and community levels 6
Minimizing Adverse Effects
- Take with food to reduce nausea, vomiting, and diarrhea 4
- Use twice-daily dosing when possible (less diarrhea than three-times-daily) 7
- Verify suspension concentration (125/31 vs 250/62) before dispensing to avoid dosing errors 1
Clinical Reassessment & Treatment Failure
Pediatric Reassessment
- At 48-72 hours: If no improvement or worsening, switch to high-dose amoxicillin-clavulanate (if not already using) or consider alternative diagnosis 1
- Clinical improvement expected within 48-72 hours of starting therapy 1
Adult Reassessment
- At 3-5 days: If no improvement, switch to high-dose amoxicillin-clavulanate or respiratory fluoroquinolone 2
- At 7 days: Persistent or worsening symptoms require diagnostic reconsideration, imaging, and ENT referral 2
When to Switch Antibiotics
- Treatment failure after 48-72 hours on standard-dose amoxicillin 1
- Worsening symptoms at any time 2
- Suspected complications: Orbital cellulitis, meningitis, severe headache, visual changes, altered mental status 2
Special Populations
Renal Impairment
In patients with renal insufficiency, prolong the dosing interval according to creatinine clearance to avoid accumulation. 1
- CrCl 10-50 mL/min: Levofloxacin 250 mg every 48 hours (if switching for treatment failure) 2
- Pediatric renal dysfunction: Significantly reduce dose due to renal elimination of both components 1
Patients ≥40 kg
Dose as an adult rather than using pediatric weight-based calculations. 2
Pregnancy & Lactation
- Generally considered safe; amoxicillin is FDA Pregnancy Category B 4
- Both components are excreted in breast milk in small amounts 4
Critical Prescribing Pitfalls to Avoid
Diagnostic Errors
- Do NOT prescribe for viral URIs: 98-99.5% of acute rhinosinusitis cases are viral 2
- Apply stringent diagnostic criteria before prescribing; antibiotics for nonspecific URI provide no benefit and only expose patients to harm 6
- Avoid antibiotics for symptom duration <10 days unless severe features present (fever ≥39°C with purulent nasal discharge for ≥3 consecutive days) 2
Dosing Errors
- Using standard doses when high-dose is indicated leads to treatment failure with resistant organisms 1
- Subtherapeutic doses fail to achieve adequate concentrations and promote antimicrobial resistance 1
- Verify suspension concentration before calculating volume to avoid dosing errors 1
Duration Errors
- Minimum treatment duration: ≥5 days for adults and ≥10 days for children to reduce relapse risk 2
- Do NOT stop antibiotics prematurely even if symptoms improve 1
Inappropriate Agent Selection
- Azithromycin is NOT first-line for any pediatric URI and provides inadequate coverage for common pathogens causing AOM and sinusitis 6
- Plain amoxicillin is insufficient when β-lactamase-producing organisms are suspected 1
Pharmacokinetic Advantages
High-dose amoxicillin (80-90 mg/kg/day) exceeds the minimum inhibitory concentration for intermediately resistant S. pneumoniae and many highly resistant serotypes. 1
- Serum levels increase linearly with dose, and the difference in adverse effects between lower and higher doses is generally negligible 1
- The 14:1 ratio formulation provides adequate middle ear fluid concentrations to overcome penicillin-resistant S. pneumoniae 1
- Predicted clinical efficacy: 90-92% for high-dose regimens versus 83-88% for standard-dose 2
- Clavulanic acid absorption is enhanced by amoxicillin 4
- Absorption not affected by food; taking with food reduces GI side effects without compromising efficacy 4
Drug Interactions
Safe Co-Administration
Clemastine (antihistamine) can be safely co-administered with amoxicillin-clavulanate for patients with concurrent allergic rhinitis and bacterial sinusitis. 2
- Sedation risk: Clemastine causes sedation intrinsic to the drug, not amplified by the antibiotic 2
- GI tolerability: Clavulanic acid causes GI adverse events in 5-13% of patients, independent of antihistamine use 2
Alternatives for Penicillin Allergy
Non-Severe (Non-Type I) Allergy
- Second- or third-generation cephalosporin (e.g., cefpodoxime with renal dose adjustment) 2
Severe (Type I/Anaphylactic) Allergy
- Adults: Respiratory fluoroquinolone (levofloxacin or moxifloxacin) 2
- Children: Clindamycin plus third-generation oral cephalosporin 2
Adjunctive Therapies
- Intranasal corticosteroids (mometasone, fluticasone, budesonide) twice daily reduce mucosal inflammation and speed symptom resolution 2
- Saline nasal irrigation 2-3 times daily provides symptomatic relief and enhances mucus clearance 2
- Analgesics (acetaminophen or ibuprofen) for pain and fever control 2