A1259802909LbajQ

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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, placebo-
• controlled 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 11.

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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
• Irritants
• Affecting data quality
• Trial specific
• Site specific

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SPECIFIC METHODOLOGICAL ISSUES

• 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.