Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia

The CAP-IT Randomized Clinical Trial

Julia A. Bielicki, PhD1; Wolfgang Stöhr, PhD2; Sam Barratt, MPH2; et al

Aim

To see if a shorter duration or lower dose of amoxicillin is non-inferior to a full 7 day course

Rationale

It is unclear which children discharged from hospital with infectious/respiratory features will benefit from antibiotics. 

Design

2x2 non-inferiority multi-centre randomised controlled trial. 

Setting

Emergency departments and wards in 28 UK and Irish hospitals. 

Population

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.

Intervention

3 days of treatment

35-50mg/kg/day6

Control

7days of oral amoxicillin 

70-90mg/kg/day

Primary outcome

Re-treatment for infection within 28 days

Results

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%)

Author's Discussion

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. 

Strengths

Randomised 

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

Weakness

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.