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


RESULTS
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.


CONCLUSIONS
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.
Centers for Disease Control and Prevention, Public Health Service, Department of Health and Human Services, Atlanta, USA. walter_straus@merck.com
W L
WL
Straus
S A
SA
Qazi
Z
Z
Kundi
N K
NK
Nomani
B
B
Schwartz
D000658:Amoxicillin / Q000627:therapeutic use*; D000668:Ampicillin Resistance; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000453:epidemiology; D002675:Child, Preschool; D003906:Developing Countries; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010154:Pakistan / Q000453:epidemiology; D010406:Penicillins / Q000627:therapeutic use; D018410:Pneumonia, Bacterial / Q000145:classification / Q000188:drug therapy* / Q000453:epidemiology; D017211:Treatment Failure; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
D000890:Anti-Infective Agents; D010406:Penicillins; D000658:Amoxicillin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination