PediCAP Trial - Impact of duration of antibiotic therapy and of oral step-down to amoxicillin or co-amoxiclav on effectiveness, safety and selection of antimicrobial resistance in severe and very severe childhood community-acquired pneumonia (CAP): a randomised controlle

Antibiotics are key to managing childhood pneumonia, especially severe/very severe pneumonia, which remains a leading cause of hospitalisation in lower/middle income countries. WHO recommends children with severe/very severe pneumonia receive injectable antibiotics for at least 5 days. One major advantage of injectable regimens is that they cover a greater spectrum of bacterial pathogens than oral amoxicillin alone.
However, this means that severe/very severe pneumonia is associated with longer hospital stays, high healthcare and societal costs, and carries an increased risk of nosocomial infection and acquisition of multidrug-resistant colonising bacteria. Currently there are no data to support a safe early step-down to oral antibiotics after initial treatment with injectable antibiotics. While step-down treatment with oral amoxicillin may be effective, co-amoxiclav, a combination of amoxicillin and a beta-lactamase inhibitor, maintains the advantage of a wider spectrum of activity provided by injectable regimens. Its potential disadvantages may be higher rates of unwanted sideeffects and selection of antimicrobial resistance (AMR). Duration of exposure is an equally important influence on AMR as longer treatment courses represent greater selection pressure on commensal flora. Limited evidence is available to define optimal duration of treatment for severe/very severe pneumonia. Especially when considering broader-spectrum antibiotics for childhood infections, such as severe/very severe pneumonia, it is essential to identify the minimum duration of treatment delivering effective cure rates, while reducing the impact of resistance and toxicity. Our overarching objective is to optimise antibiotic treatment for children aged 3 months to 10 years hospitalised with severe/very severe community-acquired pneumonia in South Africa, Uganda, Zambia and Zimbabwe by answering the following questions in a randomised trial using an innovative duration-responsedesign:
1. Is the rate of clinical cure superior with co-amoxiclav vs amoxicillin oral step-down therapy?
2. What is the optimal antibiotic treatment duration that achieves high rates of clinical cure while minimising length of hospital stay, toxicity and antimicrobial resistance?
3. Does this optimal duration vary by key characteristics, such as age or severity, suggesting that antibiotic duration should be personalised to specific subgroups?
These directly address the call topic by optimising treatment for lower respiratory tract infections (LRTI) in children in sub-Saharan Africa, and the EDCTP strategic research agenda for LRTI through “evaluating the efficacy of short duration antibiotic treatment regimens for community acquired LRTI (or CAP)”. We will also provide pharmacokinetic data on dispersible oral formulations of co-amoxiclav tested within the trial and determine health economic and household equity outcomes.

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