Erythromycin and Infantile Hypertrophic Pyloric Stenosis

Abstract & Commentary

Synopsis: A retrospective study of 14,876 newborns found that infants prescribed systemic erythromycin during the first 2 weeks of life had a significantly increased risk of developing infantile hypertrophic pyloric stenosis.

Source: Mahon BE, Rosenman MB, Kleiman MB. J Pediatr. 2001;139:380-384.

A retrospective cohort study of 14,876 infants born from June 1993 through December 1999 found 43 (0.29%) developed infantile hypertrophic pyloric stenosis (IHPS). The highest risk was with systemic erythromycin use during the first 2 weeks of life, with a relative risk (RR) of 10.51 (95% CI, 4.48, 24.66). Prescriptions for longer treatment periods were associated with higher risk; 6 (3%) of the 201 infants with prescriptions for > 14 days developed IHPS. Erythromycin ophthalmic ointment was not associated with an increased risk for IHPS. Only 6 infants received azithromycin, none of which developed IHPS. No infants were prescribed clarithromycin. Maternal macrolide antibiotics (erythromycin, azithromycin, or clarithromycin) administered within 10 weeks of delivery may have been associated with higher risk of IHPS (RR 1.47; 95% CI 0.7, 3.3).

Comment by Hal B. Jenson, MD, FAAP

An association of erythromycin and IHPS was first reported in 1976 by SanFilippo.1 In 1999, another report of a cluster of cases of IHPS among infants treated with erythromycin after exposure to pertussis found an absolute risk of IHPS of 4.5% among the 157 infants treated with erythromycin compared to no cases among 125 untreated control infants.2 This new study confirms the association of erythromycin use during early infancy with IHPS. There is a plausible biologic basis for this association. Erythromycin is a motilin agonist and at doses used as an antibiotic can result in strong, nonprogagated contractions that may lead to hypertrophy of the pylorus.

Erythromycin (40-50 mg/kg/d in 4 divided doses for 14 days; maximum, 2 g/d) is the recommended drug in children for treatment of pertussis and prophylaxis following exposure to pertussis. Studies suggest that the newer drugs azithromycin (10-12 mg/kg/d orally in 1 dose) or clarithromycin (15-20 mg/kg/d orally in 2 divided doses; maximum, 1 g/d), may be effective in shorter courses of 5-7 days; however, their efficacy is unproven. The risk of IHPS after treatment with these drugs is unknown. Trimethoprim-sulfamethoxazole is another possible alternative, but its efficacy is also unproven. Since alternative therapies are not as well studied, the American Academy of Pediatrics continues to recommend erythromycin for treatment and prophylaxis of disease caused by B pertussis.

Erythromycin (50 mg/kg/d in 4 divided doses for 14 days) is also recommended in infants for treatment of Chlamydia trachomatis infection, which is the most common cause of afebrile pneumonia in early infancy and causes 20-30% of all pneumonia among hospitalized infants < 6 months of age. However, this usually has onset from 4-18 weeks of age (median, 9 weeks), apparently beyond the period of greatest risk for erythromycin-associated IHPS. The American Academy of Pediatrics continues to recommend erythromycin for treatment of C trachomatis infection in infants.

Despite the historically safe record of erythromycin, it should be used with prudence in early infancy. Physicians who prescribe erythromycin—and possibly other macrolides—to newborns and young infants should be aware of this association with IHPS and inform parents about the potential risks of developing IHPS and the signs of IHPS. Reports of IHPS associated with erythromycin can be reported to MedWatch, the Food and Drug Administration (FDA) Medical Products Reporting Program (by fax at 800-FDA-0178), or by using the interactive form on the MedWatch website (www.fda.gov/medwatch).

References

1. SanFilippo JA. J Pediatr Surg. 1976;11:177-180.

2. Honein MA, et al. Lancet. 1999;354:2101-2105.

Dr. Jenson, Chief, Pediatric Infectious Diseases, University of Texas Health Sciences Center, San Antonio, is Associate Editor of Infectious Disease Alert.