Oral step-down, optimal drug and total duration of antibiotic treatment in African children hospitalised with severe community-acquired pneumonia: a factorial randomised controlled trial

Bielicki, J; Clements, M; Musiime, V; Moore, DP; Sidat, M; Mulenga, V; Mutata, C; Nalwanga, D; Waggie, Z; Chilundo, J; Chabala, C; Bwakura-Dangarembizi, M; Archary, M; Kiggwe, A; Dangor, Z; Spittle, B; Kapasa, M; Tagoola, A; Jeki, C; Sacarlal, J; Buck, CW; Chanda, S; Mujuru, H; Giaquinto, C; Madhi, SA; Walker, AS; Sharland, M

Journal article

Oral step-down, optimal drug and total duration of antibiotic treatment in African children hospitalised with severe community-acquired pneumonia: a factorial randomised controlled trial

Abstract:: Background
World Health Organization (WHO) recommends five days intravenous (IV) antibiotics for children hospitalised with severe community-acquired pneumonia (CAP). Safety of step-down to different oral antibiotics and shortest effective duration are unknown.
Methods
PediCAP was an open-label, parallel group, 2x5 factorial trial randomising children 2 months-6 years hospitalised with severe CAP in five sub-Saharan African countries initiating IV antibiotics to step-down to oral amoxicillin versus 7:1 amoxicillin-clavulanate dispersible tablets (superiority comparison) for five total (IV+oral) durations (4-8 days, non-inferiority comparison), versus 5-day fixed-duration IV-only treatment (non-inferiority comparison). Children were stepped down when clinically improved and able to take oral antibiotics. Clinicians could change antibiotics if clinically indicated. The primary outcome was 28-day readmission-or-death (non-inferiority margin versus IV-only +10%).
Findings
Primary outcome was available in 1055/1101 (96%) children randomised. Mean days antibiotic exposure was 6·0, 6·8, 7·4, 8·3, 9·2 days in the 4-, 5-, 6-, 7-, 8-day arms, respectively (global-p<0·0001), with 140 (69%), 151 (76%), 167 (85%), 179 (90%), 186 (92%) stepping down within their randomised duration (global-p<0·0001). Primary outcomes occurred in 33/475 (7%), 27/484 (6%) and 6/96 (6%) in amoxicillin-clavulanate, amoxicillin and IV-only arms, respectively, with both oral step-down strategies non-inferior to IV-only (upper 95% CI +6·0%, +5·7%, respectively) and no evidence of amoxicillin-clavulanate superiority over amoxicillin (difference +1·3% (95% CI -1·8%, +4·4%), p=0·40). Primary outcomes occurred in 8/194 (4%), 10/190 (5%), 16/188 (9%), 16/193 (8%) and 10/194 (5%) in the 4-, 5-, 6-, 7-, 8-day arms, respectively; all durations were non-inferior to eight days (upper 95% CI ≤+6·0%). There was no evidence of consistent differences in adverse events for oral antibiotic or duration comparisons.
Interpretation
For sub-Saharan African children hospitalised with severe CAP without complicating factors, a strategy of stepping down upon clinical improvement to oral amoxicillin after initial IV antibiotics, with a total treatment duration of 4-5 days, is non-inferior to WHO-recommended 5-day IV treatment, both guided by clinical judgement.
Funding Funded by EDCTP2, grant RIA2017MC-2023, ISRCTN63115131.

Publication status:: Accepted

Peer review status:: Peer reviewed

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APA Style

Bielicki, J., Clements, M., Musiime, V., Moore, D. P., Sidat, M., Mulenga, V., Mutata, C., Nalwanga, D., Waggie, Z., Chilundo, J., Chabala, C., Bwakura-Dangarembizi, M., Archary, M., Kiggwe, A., Dangor, Z., Spittle, B., Kapasa, M., Tagoola, A., Jeki, C., … Sharland, M. (2026). Oral step-down, optimal drug and total duration of antibiotic treatment in African children hospitalised with severe community-acquired pneumonia: a factorial randomised controlled trial. Lancet.

MLA Style

Bielicki, J, et al. “Oral Step-down, Optimal Drug and Total Duration of Antibiotic Treatment in African Children Hospitalised with Severe Community-Acquired Pneumonia: a Factorial Randomised Controlled Trial.” Lancet, 2026.

Chicago Style

Bielicki, J, M Clements, V Musiime, et al. 2026. “Oral Step-down, Optimal Drug and Total Duration of Antibiotic Treatment in African Children Hospitalised with Severe Community-Acquired Pneumonia: a Factorial Randomised Controlled Trial.” Lancet.
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