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August, 2006

Literature Review

Single-Dose Azithromycin for the Treatment of Cholera in Adults
Go to full text in PubMed: Saha D, Karim MM, Khan WA, et al. N Engl J Med 2006;354:2452

The report is from the International Center for Diarrhoeal Disease Research, Dhaka, Bangladesh and Oxford. The study was designed to compare azithromycin vs. ciprofloxacin for treatment of severe cholera caused by Vibrio cholerae 01 or 0139. 

Methods: This was a double-blind, randomized trial in which patients received either azithromycin or ciprofloxacin in a dose of 1 gm. Participants were hospitalized on a study ward for a period of five days. During this time, they had daily stool cultures and monitoring for the frequency, volume and duration of watery stool and the frequency, volume and duration of vomiting. 

Results: The outcome with azithromycin was significantly better in terms of clinical success (defined as cessation of watery stools within 48 hours) and bacteriologic success (negative stool cultures within 48 hours) as the primary outcome measurements. Azithromycin was also superior in terms of virtually all secondary outcome measurements including duration of diarrhea, number of stools, IV fluid requirements, amount of vomitus, amount of watery stool, requirement for oral rehydration, weight change and frequency of bacteriologic relapse. These data are summarized in the following table:

 Outcomes

Azithromycin
n = 97

Ciprofloxacin
n = 98

 Primary Outcome
   Clinical success
   Bacteriologic success


71 (73%)
76 (78%)


26 (27%)*
10 (10%)*

 Secondary Outcome
   Duration diarrhea (hr. median)
   No. stools (median)
   IV fluids no.
   Watery stool (ml/kg median)
   Vomitus (ml/kg median)
   Oral rehydration (median)
   Weight change (kg)
   Bacteriologic relapse


30
36
19%
114
0
802
+ 0.08
3 (3%)


78*
52*
49%*
322*
28*
1369*
-0.36
9 (10%)

P = < 0.001

Conclusions: The authors conclude that azithromycin is superior to ciprofloxacin in treatment of cholera in Bangladesh. They attribute this in part to diminished in vitro activity of ciprofloxacin vs. V. cholerae 01 strains which are present locally. They also acknowledge that now there is emerging resistance to azithromycin as well.  Consequently, they emphasize the need for monitoring antibiotic resistance as treatment strategies evolve.

Literature Review by John G. Barlett, M.D. Professor, Division of Infectious Diseases

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