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).
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.
Asghar
Rai
R
Rawalpindi General Hospital, Rawalpindi, Pakistan.
Banajeh
Salem
S
Egas
Josefina
J
Hibberd
Patricia
P
Iqbal
Imran
I
Katep-Bwalya
Mary
M
Kundi
Zafarullah
Z
Law
Paul
P
MacLeod
William
W
Maulen-Radovan
Irene
I
Mino
Greta
G
Saha
Samir
S
Sempertegui
Fernando
F
Simon
Jonathon
J
Santosham
Mathuram
M
Singhi
Sunit
S
Thea
Donald M
DM
Qazi
Shamim
S
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
D005839:Gentamicins; D002701:Chloramphenicol; D000667:Ampicillin