Adherence to oral amoxicillin dispersible tablets in children with community-acquired pneumonia enrolled in clinical trials in Malawi

Abstract

Pneumonia remains the leading infectious cause of child mortality worldwide. Despite highly effective interventions to prevent and treat pediatric pneumonia, globally, it is estimated that only 60% of children under 5 years of age with symptoms of pneumonia are taken to a healthcare provider [1]. Healthcare provider adherence with pneumonia treatment guidelines is reported to be poor in many settings, preventing some children who do visit a healthcare setting from receiving appropriate antibiotics. Furthermore, among those who are prescribed antibiotics, patient adherence to the complete treatment course is also frequently reported to be poor. As part of our Innovative Treatments in Pneumonia (ITIP) project, we conducted a secondary analysis to assess factors associated with adherence to amoxicillin DT in the setting of clinical trials [2, 3]. The ITIP project was conducted at Kamuzu Central Hospital and Bwaila District Hospital in Lilongwe, Malawi between June 2016 and April 2019 and included two prospective, double-blind, randomized controlled clinical trials evaluating the duration of amoxicillin dispersible tablet (DT) treatment for non-severe community-acquired pneumonia among children 2–59 months of age. Children in the ITIP1 fast-breathing pneumonia trial were randomized to either placebo DT (intervention) or amoxicillin DT (control) administered twice daily for 3 days, and children in the ITIP2 chestindrawing pneumonia trial were randomized to either 3 (intervention) or 5 (control) days of twice-daily amoxicillin DT, with those in the 3-day group receiving placebo for the last 2 days of study participation. Adherence was defined as the proportion of study drug doses taken by the enrolled child of those that were expected; children who were switched to a different course of antibiotics or otherwise experienced treatment failure were not expected to continue the original course of study drug, and thus doses after such events were not counted toward the adherence denominator. For example, if an ITIP1 study participant was switched to a different treatment course after dose 4 and ingested 3 out of 4 expected study drug doses, their adherence was 75%. Similarly, if an ITIP2 study participant was switched to a different treatment course after dose 6 and ingested 3 out of 6 expected study drug doses, their adherence was 50%. Upon enrollment and randomization, the blinded study staff prepared and administered the first dose of study drug and instructed the caregiver how to administer the remaining doses using customized job aids and patient instructions with pictograms [4]. Children were kept under observation in the hospital (2–24 h in ITIP1 and 48 h in ITIP2) and assessed for treatment failure prior to discharge. Instructions on how to administer the study drug were repeated at each visit. Children were followed in the hospital, in the clinic, or at home if they missed their scheduled clinic visits for 14 days with follow-up visits at Days