Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children

Amy-Sarah Ginsburg, M.D., M.P.H., Tisungane Mvalo, M.M.E.D., Evangelyn Nkwopara, M.S., Eric D. McCollum, M.D., Melda Phiri, M.B., B.S., Robert Schmicker, M.S., Jun Hwang, M.S., Chifundo B. Ndamala, Dip., Ajib Phiri, M.D., Norman Lufesi, M.Phil., and Susanne May, Ph.D.

Aim

To see if 3 day course of amoxicillin is non-inferior to a 5 day course of amoxicillin for children with pneumonia and chest indrawing (marker for severity)

Rationale

The WHO recommends a 5 day course of amoxicillin for paediatric pneumonia with indrawing and a 3 day regime if just fast breathing. However there is significant uncertainty whether these antibiotics are necessary. 

Design

Double-blinded randomised controlled trial 

Non-inferiority

Power for 50% inferiority margin 

Setting

Outpatient department of 2 hospitals in Lilongwe, Malawi. 

Population

3000 children 

Inclusion; Aged 2-59 months, WHO criteria of chest indrawing pneumonia 

Exclusion; HIV, severe anaemia, severe respiratory distress, cough >14 days, recent antibiotic use. 

Intervention

3 days of oral amoxicillin (dosed by age)

Control

5 days of oral amoxicillin (dosed by age)

Most patients hospitalised until day 3

Primary outcome

Treatment failure by day 6 . 

Results

5.9% of children in the 3 day group had treatment failure

5.25 of children in the 5 day group had treatment failure 

An absolute difference of 0.7%

Slightly larger absolute difference of 1.1% at day 14

Similar adverse events (9.8% in day 3, 8.8% day 5)

Author's Discussion

3 days of amoxicillin is non-inferior to 5 days in non-immunocompromised children with chest indrawing pneumonia.

They draw attention to previous research suggesting that a significant proportion of pneumonias are viral and the disease should be viewed as a continuum 

Strengths

Randomised 

Impressively large study

Power calculation based on previous research 

Intention to treat analysis 

Low numbers of loss to follow up

Weakness

Large inferiority margin (50%) (although author’s provide rationale)

High percentage of treatment failure in both groups

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. However, chest in-drawing pneumonia are normally classified as quite unwell. 

I noted that the majority of patients were admitted. Therefore if I had the ability to watch the patient for a few days I would be happy to discharge without any further antibiotics after 3 days.  Depending on the admitting capabilities of where I would be working, it also seems a simple message to provide to care-givers that if still unwell after 3 days of treatment to return, and can switch to second-line/intravenous antibiotics at this stage.