title: Chloramphenicol versus ampicillin plus gentamicin for community acquired very severe pneumonia among children aged 2-59 months in low resource settings: multicentre randomised controlled trial (SPEAR study).
abstract: OBJECTIVE
  To evaluate whether five days' treatment with injectable ampicillin plus gentamicin compared with chloramphenicol reduces treatment failure in children aged 2-59 months with community acquired very severe pneumonia in low resource settings.
  
  
  METHODS
  Open label randomised controlled trial.
  
  
  METHODS
  Inpatient wards within tertiary care hospitals in Bangladesh, Ecuador, India, Mexico, Pakistan, Yemen, and Zambia.
  
  
  METHODS
  Children aged 2-59 months with WHO defined very severe pneumonia.
  
  
  METHODS
  Chloramphenicol versus a combination of ampicillin plus gentamicin.
  
  
  METHODS
  Primary outcome measure was treatment failure at five days. Secondary outcomes were treatment failure defined similarly among all participants evaluated at 48 hours and at 10 and 21 days.
  
  
  RESULTS
  More children failed treatment with chloramphenicol at day 5 (16% v 11%; relative risk 1.43, 95% confidence interval 1.03 to 1.97) and also by days 10 and 21. Overall, 112 bacterial isolates were obtained from blood and lung aspirates in 110 children (11.5%), with the most common organisms being Staphylococcus aureus (n=47) and Streptococcus pneumoniae (n=22). In subgroup analysis, bacteraemia with any organism increased the risk of treatment failure at 21 days in the chloramphenicol group (2.09, 1.41 to 3.10) but not in the ampicillin plus gentamicin group (1.12, 0.59 to 2.13). Similarly, isolation of S pneumoniae increased the risk of treatment failure at day 21 (4.06, 2.73 to 6.03) and death (5.80, 2.62 to 12.85) in the chloramphenicol group but not in the ampicillin plus gentamicin group. No difference was found in treatment failure for children with S aureus bacteraemia in the two groups, but the power to detect a difference in this subgroup analysis was low. Independent predictors of treatment failure by multivariate analysis were hypoxaemia (oxygen saturation <90%), receiving chloramphenicol, being female, and poor immunisation status.
  
  
  CONCLUSIONS
  Injectable ampicillin plus gentamicin is superior to injectable chloramphenicol for the treatment of community acquired very severe pneumonia in children aged 2-59 months in low resource settings.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN39543942.
authors.affiliation: Rawalpindi General Hospital, Rawalpindi, Pakistan.
authors.forename: Rai
authors.initials: R
authors.lastname: Asghar
authors.forename: Salem
authors.initials: S
authors.lastname: Banajeh
authors.forename: Josefina
authors.initials: J
authors.lastname: Egas
authors.forename: Patricia
authors.initials: P
authors.lastname: Hibberd
authors.forename: Imran
authors.initials: I
authors.lastname: Iqbal
authors.forename: Mary
authors.initials: M
authors.lastname: Katep-Bwalya
authors.forename: Zafarullah
authors.initials: Z
authors.lastname: Kundi
authors.forename: Paul
authors.initials: P
authors.lastname: Law
authors.forename: William
authors.initials: W
authors.lastname: MacLeod
authors.forename: Irene
authors.initials: I
authors.lastname: Maulen-Radovan
authors.forename: Greta
authors.initials: G
authors.lastname: Mino
authors.forename: Samir
authors.initials: S
authors.lastname: Saha
authors.forename: Fernando
authors.initials: F
authors.lastname: Sempertegui
authors.forename: Jonathon
authors.initials: J
authors.lastname: Simon
authors.forename: Mathuram
authors.initials: M
authors.lastname: Santosham
authors.forename: Sunit
authors.initials: S
authors.lastname: Singhi
authors.forename: Donald M
authors.initials: DM
authors.lastname: Thea
authors.forename: Shamim
authors.initials: S
authors.lastname: Qazi
mesh_terms: D000667:Ampicillin / Q000008:administration & dosage*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D002675:Child, Preschool; D002701:Chloramphenicol / Q000008:administration & dosage*; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D003906:Developing Countries; D004359:Drug Therapy, Combination; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D008297:Male; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D017211:Treatment Failure
chemical_list: D005839:Gentamicins; D002701:Chloramphenicol; D000667:Ampicillin