What antibiotics are less likely to cause gastrointestinal upset in children with pneumonia?

Antibiotics with Lower GI Upset Risk in Pediatric Pneumonia

Azithromycin causes significantly less gastrointestinal upset than amoxicillin-clavulanate in children with pneumonia, making it the preferred choice when GI tolerability is a priority.

Evidence-Based GI Tolerability Profile

Azithromycin: Best GI Tolerability

• Azithromycin demonstrates superior GI tolerability with treatment-related adverse events occurring in only 11.3% of children compared to 31% with amoxicillin-clavulanate or erythromycin 1
• The FDA label reports gastrointestinal side effects in approximately 18% of azithromycin-treated patients versus higher rates with comparators 2
• Specific GI symptoms with azithromycin include diarrhea (6-9%), vomiting (6%), and abdominal pain (3-4%), which are generally mild to moderate 2, 3
• On average, only 9% of pediatric patients experience treatment-related adverse events with azithromycin, and these very seldom necessitate treatment withdrawal 3

Amoxicillin: Moderate GI Tolerability

• Plain amoxicillin (without clavulanate) is well-tolerated and recommended as first-line therapy for children under 5 years 4, 5
• The British Thoracic Society specifically notes that amoxicillin is "well tolerated" in addition to being effective and inexpensive 4
• Amoxicillin alone has significantly better GI tolerability than amoxicillin-clavulanate combinations 2

Amoxicillin-Clavulanate: Higher GI Upset

• Amoxicillin-clavulanate causes substantially more GI side effects, with diarrhea occurring in 32% versus 17% with azithromycin, and nausea in 12% versus 7% 2
• The overall incidence of treatment-related adverse events with amoxicillin-clavulanate reaches 51% compared to 31% with azithromycin 2

Erythromycin: Highest GI Upset

• Erythromycin has considerably more frequent side effects and treatment discontinuations compared to both azithromycin and plain amoxicillin 6
• A 1982 study found that discontinuation of therapy and unacceptable side effects were "considerably more frequent with amoxicillin than with erythromycin ethylsuccinate," though this predates modern formulations 6

Clinical Algorithm for Antibiotic Selection Based on GI Tolerability

For Children <5 Years Old:

1. First choice: Plain amoxicillin (90 mg/kg/day in 2 doses) - provides excellent coverage for S. pneumoniae with good GI tolerability 4
2. If GI upset is a major concern or atypical pathogens suspected: Azithromycin (10 mg/kg day 1, then 5 mg/kg days 2-5) 4, 1
3. Avoid: Amoxicillin-clavulanate unless specifically indicated - reserve for treatment failures or specific clinical scenarios 4

For Children ≥5 Years Old:

1. First choice: Azithromycin - covers both typical and atypical pathogens with lowest GI side effect profile 4, 1
2. Alternative: Plain amoxicillin if S. pneumoniae strongly suspected 4
3. Avoid: Erythromycin - use clarithromycin if azithromycin unavailable 4

Important Clinical Pitfalls

Clavulanate is the Culprit

• The clavulanate component, not amoxicillin itself, causes the majority of GI side effects in combination products 2
• When prescribing for pneumonia, use plain amoxicillin rather than amoxicillin-clavulanate unless there are specific indications for broader coverage 4

Macrolide Selection Matters

• Among macrolides, azithromycin and clarithromycin are better tolerated than erythromycin 4, 7
• Azithromycin requires less frequent dosing (once daily) which improves compliance and reduces cumulative GI exposure 7, 1

Age-Appropriate Pathogen Coverage

• While azithromycin has better GI tolerability, plain amoxicillin remains first-line for children <5 years because S. pneumoniae is the predominant pathogen and amoxicillin provides superior coverage 4, 5
• For children ≥5 years, the increased prevalence of Mycoplasma pneumoniae makes azithromycin both more appropriate for coverage and better tolerated 4, 8

Monitoring and Management

• If a child remains unwell or develops worsening GI symptoms 48 hours after starting antibiotics, re-evaluation is necessary 4, 9
• Treatment-related GI symptoms with azithromycin are typically mild and self-limited, rarely requiring discontinuation 3, 1