Which antibiotic most commonly causes vomiting in pediatric patients?

Erythromycin Most Commonly Causes Vomiting in Pediatric Patients

Erythromycin is the macrolide antibiotic most strongly associated with vomiting and gastrointestinal side effects in children, occurring in up to 70% of patients, significantly more than clarithromycin or azithromycin. 1

Comparative Gastrointestinal Toxicity Among Macrolides

The macrolide class demonstrates a clear hierarchy of gastrointestinal side effects in pediatric populations:

• Erythromycin causes the highest incidence of nausea, vomiting, abdominal pain, and diarrhea among all macrolides, with gastrointestinal symptoms reported in up to 70% of patients 1
• Clarithromycin produces moderate gastrointestinal effects with overall adverse effect rates of 14-26% in children 2
• Azithromycin demonstrates the most favorable profile with adverse effect rates of 6-27%, and is associated with significantly lower incidence of gastrointestinal side effects compared to erythromycin 3, 2

Mechanism of Erythromycin-Induced Vomiting

The gastrointestinal toxicity is not due to alterations in gut flora as originally thought, but rather:

• Erythromycin acts through direct interactions with motilin receptors in the gut, potentiating gastric and small bowel motility, increasing lower esophageal sphincter pressure, and influencing colonic transit 1
• This prokinetic effect is so pronounced that erythromycin is therapeutically used for conditions with reduced gastrointestinal motility, including diabetic gastroparesis and postoperative ileus 1
• Intravenous erythromycin causes gastrointestinal toxicity in 53% of hospitalized patients, with clinically important toxicity (severe enough to consider discontinuation) occurring in 37% 4

Age-Related Vulnerability

Younger patients are significantly more susceptible to erythromycin-induced vomiting:

• Among patients under age 40,67% experienced gastrointestinal toxicity compared to only 28% of patients over age 40 (p = 0.018) 4
• This age-related pattern makes erythromycin particularly problematic in pediatric populations 4

Clinical Implications and Mitigation Strategies

When erythromycin must be used despite its gastrointestinal effects:

• Dose reduction may improve tolerability, though this may also reduce clinical efficacy 1
• For intravenous administration, prolonging infusion time to 60 minutes combined with glycopyrrolate 0.1 mg IV pretreatment reduces clinically important toxicity by 79% (from 47% to 10%, p = 0.007) 4
• Patients should be warned of gastrointestinal side effects prior to initiating therapy 1
• Clinicians should carefully consider the risk-to-benefit balance when prescribing for patients with pre-existing gastrointestinal symptoms 1

Preferred Alternatives in Pediatric Practice

The newer macrolides azithromycin and clarithromycin should be preferentially selected over erythromycin when macrolide therapy is indicated in children:

• Both demonstrate superior tolerability profiles with lower rates of drug discontinuation due to side effects 3, 2
• Azithromycin shows no significant drug interactions, unlike erythromycin which has contraindications with theophylline, carbamazepine, warfarin, cyclosporine, terfenadine, and digoxin 3, 2
• For children ≥5 years with pneumonia, macrolides (azithromycin, clarithromycin, or erythromycin) are first-line empirical treatment, but azithromycin or clarithromycin are preferred over erythromycin due to better tolerability 5