Transcript Oral presentation 2

Exploring Alternative Antibiotic
Treatment Regimens: Methodology
and Implications
Dr. Tabish Hazir
MASCOT Study Group
2nd ICIUM Conference 2004
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BACKGROUND
 To reduce ARI mortality WHO introduced standardised case
management guidelines.
 Amoxicillin and cotrimoxazole are recommended as first line
treatment for non-severe pneumonia.
 The currently recommended duration of therapy is 5 days.
 This recommendation is not based on strong scientific evidence.
 Shorter antibiotic courses have shown to be effective in the
treatment of otitis media, sinusitis and tonsillopharyngitis.
 If effective, shorter antibiotic course for treatment of
pneumonia will have important policy implications.
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BACKGROUND
Contd.
 Patients tend to stop treatment once they are better which
results in non-adherence.
 Shorter course antibiotic therapy for non-severe pneumonia
would have many advantages:
a. Reduce the cost of treatment
b. Enhance patient compliance.
c. Contribute towards containment of antimicrobial resista
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METHODOLOGY
• It was an equivalence, randomized, double blind, placebocontrolled trial.
• Carried out in the outpatient departments of 6 hospitals in
Gilgit, Islamabad, Lahore, Multan and Rawalpindi.
• All children with cough and/or difficult breathing were
screened by specially hired and trained study physicians at
each site.
• Children diagnosed to have WHO defined “non-severe
pneumonia” were enrolled.
• Randomization scheme was developed at WHO, Geneva for
each site using uneven blocks of 2, 4, 6 for both groups in
ratio of 1:1.
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METHODOLOGY
• Each of the study patients received two medicine bottles,
labeled ‘Green’ containing active drug for first 3 days and
‘Red’ containing either placebo or active drug for next 2 days.
• Follow-ups were done on day 3, 6, and 14.
• Antibiotic was changed to oral Chloramphenicol in children
who did not show improvement.
• Children who showed deterioration at any stage were
admitted for injectible antibiotics.
• All children were followed up by study physicians till they
were cured.
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INCLUSION CRITERIA
• Age 2-59 months.
• History of cough and/or difficult breathing.
• Diagnosis of WHO defined non - severe pneumonia.
EXCLUSION CRITERIA
• Signs of WHO defined severe pneumonia or very severe disease.
• Known penicillin allergy.
• Complicating acute non-pulmonary or chronic illness.
• Living outside the municipal limits of city.
• Taken the appropriate doses of WHO recommended antimicrobial
drugs
for 48 hours prior to presentation.
• Prior history of wheezing or bronchial asthma and wheezing now.
• Previously enrolled patients in the present study.
• Whose parents/guardian refuse to give consent.
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SAMPLE SIZE
• Sample size was calculated to show a point estimate of
clinical failure rate.
• We assume the two modes of therapy to be equal, if the
failure rate between the two regimens is within 5%.
• For an alpha of 0.03 and a power of 90% the required
sample size was 845 in each group.
• With inclusion of 15% loss to follow-up the total estimated
sample size was 1954.
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METHODOLOGICAL ISSUES
•
GENERAL
•
SPECIFIC
1. Irritants
2. Affecting data quality
a. Trial specific
b. Site specific
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SPECIFIC METHODOLOGICAL
ISSUES
1. TRAINING:
a. Site study physicians.
b. Lady Health Workers (LHWs).
2. HOME FOLLOW-UPS.
3. 14 DAY FOLLOW-UP:
Delay in communication and feedback
4. STANDARDIZATION OF RADIOLOGICAL
INTERPRETATION.
5. MICROBIOLOGY.
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