What is the next step in treating an ear infection in a patient with no improvement after 3 days on Augmentin (amoxicillin/clavulanate)?

Treatment Failure After 3 Days of Augmentin for Ear Infection

If an ear infection has not improved after 3 days of Augmentin (amoxicillin-clavulanate), you should switch to intramuscular ceftriaxone 50 mg/kg daily for 3 consecutive days. 1

When to Change Antibiotics

• An alternative management strategy is warranted when symptoms fail to improve after 3-5 days of initial empiric antimicrobial therapy 1
• The 3-day mark is the critical decision point—if no clinical improvement is evident, continuing the same antibiotic is unlikely to succeed 1
• For children under 2 years with acute otitis media, antibiotic therapy should always be given, making treatment failure particularly concerning 1

Recommended Second-Line Treatment

The preferred second-line option is ceftriaxone 50 mg/kg intramuscularly or intravenously once daily for 3 consecutive days 1. This provides:

• Excellent coverage against resistant Streptococcus pneumoniae (the most common pathogen in treatment failures) 1
• High middle ear fluid concentrations with once-daily dosing 1
• Coverage for β-lactamase-producing Haemophilus influenzae strains that may have caused the initial treatment failure 1

Alternative Oral Options (If Injectable Route Not Feasible)

If intramuscular ceftriaxone is not practical, consider these oral alternatives:

• Cefdinir 14 mg/kg per day in 1-2 doses 1
• Cefuroxime 30 mg/kg per day in 2 divided doses 1
• Cefpodoxime 10 mg/kg per day in 2 divided doses 1

These cephalosporins have distinct chemical structures from penicillins and are highly unlikely to cause cross-reactivity even in penicillin-allergic patients 1.

What NOT to Do: Critical Pitfalls

• Never prescribe the same antibiotic at the same dose that already failed 2—this is the most common error
• Do not use azithromycin or other macrolides as second-line therapy, as they have inferior efficacy against S. pneumoniae compared to high-dose amoxicillin-clavulanate 1
• Avoid simply extending the duration of Augmentin without changing the antibiotic 1

If Second-Line Treatment Also Fails

After 48-72 hours of ceftriaxone (or alternative second-line agent), if symptoms persist or worsen 1:

1. Perform tympanocentesis (if skilled) or refer to ENT for middle ear fluid aspiration and culture 1
2. Consider clindamycin 30-40 mg/kg per day in 3 divided doses PLUS a third-generation cephalosporin to cover potential resistant organisms 1
3. Obtain direct sinus aspiration cultures rather than nasopharyngeal swabs, as nasopharyngeal cultures are unreliable 1

Why Augmentin Fails

Understanding the mechanism helps guide treatment:

• 58-82% of H. influenzae isolates remain susceptible to amoxicillin, meaning 18-42% produce β-lactamase and are resistant 1
• Some S. pneumoniae strains have intermediate or high-level penicillin resistance 1
• Recent antibiotic use (within 30 days) significantly increases the risk of resistant organisms 1, 2
• Concurrent purulent conjunctivitis suggests H. influenzae as the pathogen, which may be β-lactamase-producing 1

Expected Timeline for Improvement

• Patients should show clinical improvement within 48-72 hours of starting appropriate antibiotic therapy 2
• Complete resolution typically occurs by 10-14 days with effective treatment 1
• If fever persists beyond 72 hours on the new antibiotic, reassessment is mandatory 1, 2

Special Considerations

• Children who received amoxicillin in the previous 30 days should have started with high-dose amoxicillin-clavulanate rather than regular amoxicillin 1
• The presence of concurrent purulent conjunctivitis (otitis-conjunctivitis syndrome) indicates likely H. influenzae and warrants immediate use of amoxicillin-clavulanate or cephalosporins 1
• Immunocompromised patients or those with recurrent treatment failures require specialist referral (ENT or infectious disease) 1