Antimicrobial resistance and clinical effectiveness of co-trimoxazole versus amoxycillin for pneumonia among children in Pakistan: randomised controlled trial. Pakistan Co-trimoxazole Study Group

Lancet. 1998 Jul 25;352(9124):270-4. doi: 10.1016/s0140-6736(97)10294-x.


Background: Co-trimoxazole is widely used in treatment of paediatric pneumonia in developing countries, but drug resistance may decrease its effectiveness. We studied the effectiveness of co-trimoxazole compared with that of amoxycillin in pneumonia therapy, and assessed the clinical impact of co-trimoxazole resistance.

Methods: We recruited 595 children, aged 2-59 months, with non-severe or severe pneumonia (WHO criteria) diagnosed in the outpatient wards of two urban Pakistan hospitals. Patients were randomly assigned on a 2:1 basis co-trimoxazole (n=398) or amoxycillin (n=197) in standard WHO doses and dosing schedules, and were monitored in study wards. The primary outcome was inpatient therapy failure (clinical criteria) or clinical evidence of pneumonia at outpatient follow-up examination.

Findings: There were 92 (23%) therapy failures in the co-trimoxazole group and 30 (15%) in the amoxycillin group (p=0.03)-26 (13%) versus 12 (12%) among children with non-severe pneumonia (p=0.856) and 66 (33%) versus 18 (18%) among those with severe pneumonia (p=0.009). For patients with severe pneumonia, age under 1 year (p=0.056) and positive chest radiographs (p=0.005) also predicted therapy failure. There was no significant association between antimicrobial minimum inhibitory concentration and outcome among bacteraemic children treated with co-trimoxazole.

Interpretation: Co-trimoxazole provided effective therapy in non-severe pneumonia. For severe, life-threatening pneumonia, however, co-trimoxazole is less likely than amoxycillin to be effective.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Amoxicillin / therapeutic use*
  • Ampicillin Resistance
  • Anti-Infective Agents / therapeutic use*
  • Bacteremia / drug therapy
  • Bacteremia / epidemiology
  • Child, Preschool
  • Developing Countries*
  • Drug Resistance, Microbial
  • Female
  • Humans
  • Infant
  • Male
  • Pakistan / epidemiology
  • Penicillins / therapeutic use
  • Pneumonia, Bacterial / classification
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / epidemiology
  • Treatment Failure
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*


  • Anti-Infective Agents
  • Penicillins
  • Amoxicillin
  • Trimethoprim, Sulfamethoxazole Drug Combination