ANTIMICROBIAL RESISTANCE AND CLINICAL EFFECTIVENESS OF COTRIMOXAZOLE VERSUS AMOXICILLIN FOR PNEUMONIA AMONG CHILDREN IN PAKISTAN - RANDOMIZED CONTROLLED TRIAL

Background Cotrimoxazole is widely used in treatment of paediatric pne umonia in developing countries, but drug resistance may decrease its e ffectiveness. We studied the effectiveness of co-trimoxazole compared with that of amoxycillin in pneumonia therapy, and assessed the clinic al impact of co-trimoxazole resistance. Methods We recruited 595 child ren, aged 2-59 months, with non-severe or severe pneumonia (WHO criter ia) 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, an d were monitored in study wards. The primary outcome was inpatient the rapy failure (clinical criteria) or clinical evidence of pneumonia at outpatient follow-up examination. Findings There were 92 (23%) therapy failures in the cotrimoxazole group and 30 (15%) in the amoxycillin g roup (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 seve re pneumonia (p=0.009). For patients with severe pneumonia, age under 1 year (p=0.056) and positive chest radiographs (p=0.005) also predict ed therapy failure. There was no significant association between antim icrobial minimum inhibitory concentration and outcome among bacteraemi c children treated with co-trimoxazole. Interpretation Co-trimoxazole provided effective therapy in non-severe pneumonia. For severe, life-t hreatening pneumonia, however, co-trimoxazole is less likely than amox ycillin to be effective.