First Nations children have one of the world’s highest published rates of hospitalised pneumonia and chronic lung disease including bronchiectasis (BE). Children from developing countries are also at a similar risk. Yet, optimal treatment of pneumonia and how to prevent its long-term effects remain unclear. Trials have focused upon short-term (1-2 weeks) outcomes and reduced antibiotic (AB) courses in children with non-severe (viral) pneumonia. However, in high-risk populations from Australia and Malaysia, a longer course of ABs may enhance bacteria clearance and thus reduce the risk of chronic lung disease after severe bacterial pneumonia in young children whose lungs are still developing.

Aims:

A double-blinded randomised controlled trial (RCT) designed to answer the following research question: Does a longer course (12-13 days) of antibiotics compared to shorter course (5-6), improve short and medium-term clinical outcomes of children hospitalised with severe community-acquired pneumonia.

Objectives:

Primary 

• Does a longer course (13-14 days) of amoxicillin-clavulanic acid, compared to a shorter course (5-6 days), improve clinical outcomes of children hospitalised with severe community-acquired CXR confirmed pneumonia?

(i)    improving clinical cure rates

(ii)    reducing risk of chronic respiratory symptoms and/or signs or bronchiectasis (at 24 months) and/or

(iii)   increasing time to the next respiratory hospitalisation

Secondary

1. Monitor the effects of the duration of antibiotic treatment on antibiotic resistance in respiratory pathogens isolated from the nasopharynx (NP).
2. Determine the predictors of chronic respiratory symptoms or bronchiectasis, specifically the contributions of:  

(i)     Host gene expression signatures associated with lower airway bacterial infection; and 

(ii)    Persistent CXR abnormalities following treatment for pneumonia.

Data from this study will substantially advance child pneumonia treatment with implications for future lung health, especially in high-risk Indigenous children. Results would lead to changes in national and international guidelines.

As a longer AB treatment for all children may increase AB resistance and lead to ‘over-treatment’ in some, we will address these two issues by monitoring for AB resistance and embark on a discovery program to identify biomarkers that predict poor long-term respiratory health outcomes. Availability of novel biomarkers from host gene expression will help clinicians decide which children are at high risk, and therefore in need of more intensive follow up, and may enable targeting of longer AB treatment to those at highest risk of BE.

Funded by: Pilot project (CRE 2012-18) and current NHMRC Project Grant

Chief Investigators: Chang AB, Grimwood K, Teo TW, Upham JW, Ooi MH, Fong S, Nathan AM, Byrnes C

Collaborating sites: Likas Hospital, Kota Kinabalu (Sabah, Malaysia), Nanyang Technological University (Singapore), Griffith University (Qld, Australia), University of Malaya (Kuala Lumpur, Malaysia), Tengku Ampuan Rahimah Hospital (Kluang, Malaysia), University of Queensland (Brisbane), University of Auckland (New Zealand).