Is shorter, lower dose amoxicillin safe in kids discharged with pneumonia in a UK setting?
Julia A. Bielicki, PhD1; Wolfgang Stöhr, PhD2; Sam Barratt, MPH2; et al
To see if a shorter duration or lower dose of amoxicillin is non-inferior to a full 7 day course
It is unclear which children discharged from hospital with infectious/respiratory features will benefit from antibiotics.
2x2 non-inferiority multi-centre randomised controlled trial.
Emergency departments and wards in 28 UK and Irish hospitals.
824 children aged >6 months of age who were planned to be discharged with antibiotics.
British thoracic society definition of pneumonia (cough+fever +laboured breathing or focal signs)
Exclusion; recent antibiotics, complicated pneumonia or underlying chronic condition.
3 days of treatment
7days of oral amoxicillin
Re-treatment for infection within 28 days
No difference between higher(12.4%) and lower dose( 12.6%) treatment failure (difference, 0.2% [1-sided 95% CI –∞ to 4.0%])
No difference between 3 days and 7 days of amoxicillin (both 12.5% treatment failure)
Amongst those with severe pneumonia (x2 deranged observations) there was a non-significance difference between low dose (17.3%) and high dose (13.5%)
Low dose or 3 days of amoxicillin is non-inferior to 7 days at higher dose. However, considerations of disease severity, setting and prior antibiotics should be considered.
Impressively large study
Power calculation based on previous research
Intention to treat analysis
Low numbers of loss to follow up
8 % seems like a small inferiority-margin with relatively benign outcome
High percentage of treatment failure in both groups
Author’s concerned that do not identify patients with confirmed pneumonia; however this increased applicability of this to everyday practice.
My humble opinion
This is an excellent, well conducted trial.
There seems to be a growing body of evidence that antibiotics do not have as much of an effect as we used to think in relatively well patients therefore shorter, twice daily courses of lower dose antibiotics seems appropriate. In the sub-group of those with x2 deranged observation markers (more severe) I would be admitted for a period of observations anyway so for my ED practice this would not change management.