title: Randomized controlled trial of standard versus double dose cotrimoxazole for childhood pneumonia in Pakistan.
abstract: OBJECTIVE
  Increasing concern over bacterial resistance to cotrimoxazole, which is recommended by WHO as a first-line drug for treating non-severe pneumonia, led to the suggestion that this might not be optimal therapy. However, changing to alternative antimicrobial agents, such as amoxicillin, is costly. We compared the clinical efficacy of twice-daily cotrimoxazole in standard versus double dosage for treating non-severe pneumonia in children.
  
  
  METHODS
  A randomized controlled multicentre trial was implemented in seven hospital outpatient departments and two community health programmes. A total of 1143 children aged 2-59 months with non-severe pneumonia were randomly allocated to receive 4 mg trimethoprim plus 20 mg sulfamethoxazole/kg of body weight or 8 mg trimethoprim plus 40 mg sulfamethoxazole/kg of body weight orally twice-daily for 5 days Treatment failure occurred when a child required a change of therapy, died or was lost to follow-up. Children required a change of therapy if their condition worsened (they developed chest indrawing or danger signs) or if at 48 hours after enrollment, their clinical condition was the same (defined as having a respiratory rate that was 5 breaths/minute higher or lower than at the time of enrollment).
  
  
  RESULTS
  The results of 1134 children were analysed: 578 were assigned to the standard dose of cotrimoxazole and 556 to the double dose. Treatment failed in 112 children (19.4%) in the standard group and 118 (21.2%) in the double-dose group (relative risk 1.10; 95% confidence interval = 0.87-1.37). Using multivariate analysis we found that treatment was more likely to fail in children who were not given the medicine correctly (P = 0.001), in those younger than 12 months (P = 0.004), those who had used antibiotics previously (P = 0.002), those whose respiratory rate was > or =20 breaths/minute above the age-specific cut-off point (P = 0.006), and those from urban areas (P = 0.042).
  
  
  CONCLUSIONS
  Both standard and double strength cotrimoxazole were equally effective in treating non-severe pneumonia. Close follow-up of patients is essential to prevent worsening of disease. Definitions of clinical failure need to be more specific. Surveillance in both rural and urban areas is essential in the development of treatment policies that are based on clinical outcomes.
authors.affiliation: Department of Community Health Sciences, Aga Khan University, House 32B Street 25, Secotr F-8-2 Islamabad, Pakistan. zeba@comstats.net.pk
authors.forename: Zeba A
authors.initials: ZA
authors.lastname: Rasmussen
authors.forename: Abdul
authors.initials: A
authors.lastname: Bari
authors.forename: Shamim
authors.initials: S
authors.lastname: Qazi
authors.forename: Gul
authors.initials: G
authors.lastname: Rehman
authors.forename: Iqbal
authors.initials: I
authors.lastname: Azam
authors.forename: SherBaz
authors.initials: S
authors.lastname: Khan
authors.forename: Farida
authors.initials: F
authors.lastname: Aziz
authors.forename: Sadia
authors.initials: S
authors.lastname: Rafi
authors.forename: Mehr Taj
authors.initials: MT
authors.lastname: Roghani
authors.forename: Imran
authors.initials: I
authors.lastname: Iqbal
authors.forename: Abdul Ghaffar
authors.initials: AG
authors.lastname: Nagi
authors.forename: Waqar
authors.initials: W
authors.lastname: Hussain
authors.forename: Nahida
authors.initials: N
authors.lastname: Bano
authors.forename: Late J C
authors.initials: LJ
authors.lastname: van Latum
authors.forename: Mushtaq
authors.initials: M
authors.lastname: Khan
mesh_terms: D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010044:Outpatient Clinics, Hospital; D010154:Pakistan; D011014:Pneumonia / Q000188:drug therapy*; D012423:Rural Health; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage* / Q000627:therapeutic use*; D014504:Urban Health
chemical_list: D015662:Trimethoprim, Sulfamethoxazole Drug Combination