Three-day amoxicillin course effective for chest-indrawing pneumonia in Malawi children

1. Three-day amoxicillin treatment for chest-indrawing pneumonia was not significantly different from five-day amoxicillin treatment in HIV-uninfected children from Malawi.

2. Relapse for pneumonia was not significantly different between treatment groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Bacterial pneumonia is one of the leading causes of death for children under the age of five. Treatment for pneumonia requires appropriate duration of antibacterial therapy to maximizing adherence and minimizing antimicrobial resistance. Currently, the World Health Organization (WHO) recommends administering a five-day course of amoxicillin for chest-indrawing pneumonia defined as cough lasting for less than 14 days or difficulty breathing with visible indrawing of the chest wall. However, it is unclear whether a five-day course is necessary for effective treatment. As such, this study compared the efficacy of three-day amoxicillin treatment to the standard five-day amoxicillin treatment for pneumonia. The study determined patients with the three-day amoxicillin treatment did not have a difference in treatment failure compared to the patients with the five-day amoxicillin treatment. This randomized trial was limited by the lack of laboratory or radiologic testing and the clinical resolution of pneumonia was dependent on the physical exam. Without access to laboratory or radiographic testing, it was unknown if the pneumonia completely resolved or if traces of the infection lingered in the lungs. Nonetheless, this study was strengthened by the high treatment adherence rates and similarly matched treatment groups.

Click to read the study, published today in NEJM

Relevant Reading: Community case management of severe pneumonia with oral amoxicillin in children aged 2-59 months in Haripur district, Pakistan: a cluster randomised trial

In-Depth [randomized controlled trial]: This randomized control trial enrolled 3000 patients in a multicenter study from two sites in Malawi. Children between the ages of 2 to 59 months who presented to the outpatient departments of Kamuzu Central Hospital and Bwaila District Hospital, and met the WHO case definition of chest-indrawing pneumonia were included in this study. The exclusion criteria for the study included children with severe diseases such as malaria, HIV, and anemia. The patients were randomized in a 1:1 ratio to receive either a three-day amoxicillin treatment regimen or a five-day amoxicillin treatment regimen. The primary outcome was treatment failure by the sixth day. Both groups demonstrated high treatment adherence with 91.6% of children receiving all doses in the three-day group and 91.8% of children receiving all doses in the five-day group. There was no significant difference in treatment failure by the sixth day between the three-day amoxicillin treatment group and five-day amoxicillin treatment group (absolute difference, 0.7%; 95% confidence interval [CI], -0.9 to 2.4). Moreover, by the fourteenth day, there was no significant difference in relapse of the infection between the three-day amoxicillin treatment group and the five-day amoxicillin treatment group (absolute difference, 1.0%; 95% CI, -0.8 to 2.9). Finally, 9.8% of children in the three-day group and 8.8% of children in the five-day group experienced at least one serious adverse event from the time of enrollment until the fourteenth day. Specifically, there was one death from pneumonia in the three-day group and two deaths, one from pneumonia and one from gastroenteritis, in the five-day group. Taken together, a three-day amoxicillin regimen was not significantly different for the treatment of chest-indrawing pneumonia compared to the five-day amoxicillin regimen.

Image: PD

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