This document describes a randomized controlled trial comparing the effectiveness of azithromycin versus ciprofloxacin for treating cholera in children. The trial aims to evaluate whether a single dose of oral azithromycin is as effective as a single dose of oral ciprofloxacin for resolving diarrhea and stopping the excretion of Vibrio cholerae in children with cholera. Over 87 children between ages 2-12 with acute watery diarrhea will be randomly assigned to receive either azithromycin or ciprofloxacin after rehydration. The primary outcomes will be clinical and bacteriological success after 72 hours. Secondary outcomes include recovery time, fluid requirements, and relapse rates, which will be compared between the

1. Single Dose Azithromycin versus
Ciprofloxacin for Cholera in
Children: A Randomized
Controlled Trial
Dr Pooja Dewan
Postgraduate student
Department of Pediatrics
University College of Medical Sciences & GTB Hospital

2. Supervisor : Dr. Piyush Gupta
Professor
Dept. of Pediatrics
UCMS & GTB Hospital
Delhi
Co-Supervisors : Dr. Shukla Das
Professor
Dept. of Microbiology
UCMS & GTB Hospital
Delhi
Dr MMA Faridi
Professor & Head
Dept. of Pediatrics
UCMS & GTB Hospital
Delhi

3. Background
• Cholera is a significant health problem in
children
• Ciprofloxacin proven an effective drug
• Emergence of flouroquinolone resistance in
Vibrio cholerae
• Alternate drug required
• Single-dose oral azithromycin shown good
results for cholera in adults
• No similar studies in Children

4. Aim: to evaluate the role of Azithromycin in
children with cholera
Primary Objective:
To compare Azithromycin with Ciprofloxacin, both as
single dose treatment, in children with cholera, in terms
of clinical success (resolution of diarrhea) and
bacteriological success (cessation of excretion of Vibrio
cholerae)
Secondary Objectives:
To compare recovery time, requirement of ORS or IV fluids, and
relapse rate

5. • Setting: Departments of Pediatrics and
Microbiology, University College of Medical
Sciences and GTB Hospital, Delhi.
• Study Design: Randomized, open labeled,
clinical controlled trial.
• Study Period: April 1, 2011-March 31, 2012
• Consent and Ethics: Written informed consent
and Institutional Ethical Clearance

6. Participants
Inclusion criteria
Children between 2-12 years with
•Acute watery diarrhea for ≤24 h
•Severe dehydration, and
•Positive for V. cholerae by HD examination or stool culture
Exclusion criteria
•Severe undernutrition
•Co-existing systemic illness
•Blood in stool
•Receiving an antibiotic/antidiarrheal within preceding 24 h

7. Sample size
• Equivalence study
• At least 87 patients in each treatment group to
show that the difference in rates of clinical
success between the two groups does not exceed
10%; Power= 80%, α error= 5%, β error= 20%
Khan WA, et al. Randomised controlled comparison of single-
dose ciprofloxacin and doxycycline for cholera caused by
Vibrio cholerae 01 or 0139. Lancet. 1996;348(9023):296-300.

8. Methods
• Randomization: Simple randomization
• Allocation by sealed envelope technique
• Intervention: Immediate rehydration (WHO Guidelines)
followed by
Oral azithromycin {20 mg/kg, dispersible tab} single dose
Oral ciprofloxacin {20mg/kg dispersible tab} single dose
• Monitoring: Every 8 hourly from time of drug delivery
• Time of discharge: 72 hours (day 3) or until resolution of
watery diarrhea, whichever is later.
• Follow-up visit on day 7

9. Bacteriological procedures
• Stool collection: Fresh stool sample/ rectal swab
• Hanging drop examination
• Transport : Alkaline peptone water or Cary Blair media.
• Stool culture: Bile salt agar, Mac Conkey agar and
thiosulphate citrate bile sucrose agar.
Incubation at 37ºC for 24 hours, followed by enrichment
(alkaline peptone water)
Serotyping: Slide agglutination test
Antimicrobial susceptibility testing: Kirby-Bauer disc
diffusion techinque

10. Outcome measures
Primary
• Clinical success (resolution
of diarrhea within 72 hrs
after the start of therapy )
• Bacteriological success
(cessation of excretion of
Vibrio cholerae by day 3)
Secondary
• Total duration of diarrhea
(recovery Time)
• Total requirement of ORS or
intravenous therapy
• Proportion of children with
clinical or bacteriological
relapse

11. Statistical analysis
• Frequency of Clinical and Bacteriological success, and
clinical or bacteriological relapse will be compared by
Chi-square or Fisher’s exact test.
• Duration of diarrhea and excretion of Vibrio and
requirement of RL and ORS will be compared by
unpaired t-test.
• Significant @ P<0.05
• Variables measured repeatedly like mean frequency of
stool (Days 1, 2, 3 and 7) and vomiting, will be analyzed
with repeated measure ANOVA at 1% level of
significance to allow for multiple comparisons.