Ambulatory short-course high-dose oral amoxicillin for treatment of severe pneumonia in children: a randomised equivalency trial.
BACKGROUND
WHO case management guidelines for severe pneumonia involve referral to hospital for treatment with parenteral antibiotics. If equally as effective as parenteral treatment, home-based oral antibiotic treatment could reduce referral, admission, and treatment costs. Our aim was to determine whether home treatment with high-dose oral amoxicillin and inpatient treatment with parenteral ampicillin were equivalent for the treatment of severe pneumonia in children.


METHODS
This randomised, open-label equivalency trial was done at seven study sites in Pakistan. 2037 children aged 3-59 months with severe pneumonia were randomly allocated to either initial hospitalisation and parenteral ampicillin (100 mg/kg per day in four doses) for 48 h, followed by 3 days of oral amoxicillin (80-90 mg/kg per day; n=1012) or to home-based treatment for 5 days with oral amoxicillin (80-90 mg/kg per day in two doses; n=1025). Follow-up assessments were done at 1, 3, 6, and 14 days after enrollment. The primary outcome was treatment failure (clinical deterioration) by day 6. Analyses were done per protocol and by intention to treat. This trial is registered, ISRCTN95821329.


RESULTS
In the per-protocol population, 36 individuals were excluded from the hospitalised group and 37 from the ambulatory group, mainly because of protocol violations or loss to follow-up. There were 87 (8.6%) treatment failures in the hospitalised group and 77 (7.5%) in the ambulatory group (risk difference 1.1%; 95% CI -1.3 to 3.5) by day 6. Five (0.2%) children died within 14 days of enrollment, one in the ambulatory group and four in the hospitalised group. In each case, treatment failure was declared before death and the antibiotic had been changed. None of the deaths were considered to be associated with treatment allocation; there were no serious adverse events reported in the trial.


CONCLUSIONS
Home treatment with high-dose oral amoxicillin is equivalent to currently recommended hospitalisation and parenteral ampicillin for treatment of severe pneumonia without underlying complications, suggesting that WHO recommendations for treatment of severe pneumonia need to be revised.
Hazir
Tabish
T
Children's Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan.
Fox
LeAnne M
LM
Nisar
Yasir Bin
YB
Fox
Matthew P
MP
Ashraf
Yusra Pervaiz
YP
MacLeod
William B
WB
Ramzan
Afroze
A
Maqbool
Sajid
S
Masood
Tahir
T
Hussain
Waqar
W
Murtaza
Asifa
A
Khawar
Nadeem
N
Tariq
Parveen
P
Asghar
Rai
R
Simon
Jonathon L
JL
Thea
Donald M
DM
Qazi
Shamim A
SA
D000284:Administration, Oral; D000658:Amoxicillin / Q000008:administration & dosage / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D018575:Home Care Services, Hospital-Based; D006760:Hospitalization; D006801:Humans; D007223:Infant; D008297:Male; D010154:Pakistan; D011014:Pneumonia / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology; D012307:Risk Factors; D012720:Severity of Illness Index; D017211:Treatment Failure
D000900:Anti-Bacterial Agents; D000658:Amoxicillin