Single Dose Azithromycin versus Ciprofloxacin for Cholera in

Children: A Randomized Controlled Trial

Dr Pooja DewanPostgraduate student

Department of PediatricsUniversity College of Medical Sciences & GTB Hospital

Supervisor : Dr. Piyush GuptaProfessorDept. of PediatricsUCMS & GTB HospitalDelhi

Co-Supervisors : Dr. Shukla DasProfessorDept. of MicrobiologyUCMS & GTB HospitalDelhi

Dr MMA FaridiProfessor & HeadDept. of PediatricsUCMS & GTB HospitalDelhi

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

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

• 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

ParticipantsInclusion 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

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.

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

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 testAntimicrobial susceptibility testing: Kirby-Bauer disc diffusion techinque

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

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.