Question

• In patients 0-18 years diagnosed with pertussis, is azithromycin as effective as erythromycin in treating pertussis with less side effects?

Clinical Bottom Lines

1. In a large randomized controlled trial of children from Canada and United States, azithromycin was as effective as erythromycin in eradicating B. pertussis on NP cultures in subjects.
2. Azithromycin causes fewer GI symptoms than erythromycin.
3. Compliance is better achieved with azithromycin than erythromycin.

Summary of Key Evidence

1. Randomized controlled trial including 477 patients from primary care practices in 11 Canadian and 1 American urban centre and randomly assigned to azithromycin (n=239) or erythromycin (n=238) treatment groups.¹
2. Of these children, 58 in the azithromycin groups and 56 in the erythromycin group had positive cultures.
3. Treatment was either 5 days of Azithromycin 10mg/kg on day1 then 5mg/kg on days 2-5 or Erythromycin estolate 40mg/kg div tid for 10 days.
4. In the culture- positive groups, cultures at the end of treatment and 1 week post-treatment were obtained. For all participants, a treatment-related adverse event (nausea, vomiting, diarrhea, GI complaint) diary and medication diary were completed by parents and reviewed with study personnel. Medication containers were also examined by the pharmacist at study completion
5. Eradication of NP bacteria was not significantly different between the azithromycin (53/53 or 53/58 ITT) and erythromycin (53/53 or 53/56 ITT) culture-positive groups. The same was true at 1 week post-treatment azithromycin (51/51 or 51/58ITT) ; erythromycin (53/53 or 53/56 ITT).
6. There were more GI adverse events in the erythromycin group than in the azithromycin group.
7. Compliance (taking 100% of prescribed dose) was significantly better for the azithromycin group (90%) than for the erythromycin group (55%).
8. Cough -related symptoms were not statistically different between the two groups at end of treatment.

Additional Comments

• Comparison in children younger than six months needs to be completed.
• Results may not be applicable to children younger than 6 months of age; there has been at least one small study⁴ which showed in children 2-28 months, there is bacterial eradication with azithromycin after 3 and 5 day courses, but up to 20% of participants experienced elevated ALT.
• To treat a 20kg child a full course of erythromycin (as per the study) would cost $3.20 (based on hospital cost for drug) vs. for azithromycin $19.60 (again based on hospital prices)
• When taking azithromycin, patients need to time doses to be 1 hour before or 2 hours after eating for better absorption, whereas erythromycin can be taken at any time.
  

Citation

1. Langley JM, Halperin SA, Boucher FD, Smith B; Azithromycin is as effective as and better
   tolerated than erythromycin estolate for the treatment of pertussis. Pediatrics 2004;114:e96-101.
2. Bace A, Zrnic T, Begovac J, Kuzmanovic N, Culig J. Short-term treatment of pertussis
   with azithromycin in infants and young children. Eur J Clin Microbiol Infect Dis. 1999 Apr;18(4):296-8.

CAT Author: Yaa Ohene-Fianko, MD

CAT Appraisers: Stephen M. Park, MD

Date appraised: May 3, 2006