Ambulatory Treatment of Fast Breathing in Young Infants Aged Shiyam S Tikmani  1 , Amber A Muhammad  2 , Yasir Shafiq  2 , Saima Shah  2 , Naresh Kumar  2 , Imran Ahmed  2 , Iqbal Azam  3 , Omrana Pasha  3 , Anita K M Zaidi  2 Affiliations Expand Affiliations 1 Departments of Paediatrics and Child Health, shiyam.sunder@aku.edu. 2 Departments of Paediatrics and Child Health. 3 Community Health Sciences, Aga Khan University, Karachi, Pakistan. PMID: 27941119 PMCID: PMC5853586 DOI: 10.1093/cid/ciw690 Free PMC article Item in Clipboard

Abstract

(See the Editorial Commentary by Jehan and Qazi on pages 190-1) BACKGROUND: Integrated Management of Childhood Illness recommends that young infants with isolated fast breathing be referred to a hospital for antibiotic treatment, which is often impractical in resource-limited settings. Additionally, antibiotics may be unnecessary for physiologic tachypnea in otherwise well newborns. We tested the hypothesis that ambulatory treatment with oral amoxicillin for 7 days was equivalent (similarity margin of 3%) to placebo in young infants with isolated fast breathing in primary care settings where hospital referral is often unfeasible.

Methods: This randomized equivalence trial was conducted in 4 primary health centers of Karachi, Pakistan. Infants presenting with isolated fast breathing and oxygen saturation ≥90% were randomly assigned to receive either oral amoxicillin or placebo twice daily for 7 days. Enrolled infants were followed on days 1-8, 11, and 14. The primary outcome was treatment failure by day 8, analyzed per protocol. The trial was stopped by the data safety monitoring board due to higher treatment failure rate and the occurrence of 2 deaths in the placebo arm in an interim analysis.

Results: Four hundred twenty-three infants fulfilled per protocol criteria in the amoxicillin arm and 426 in the placebo arm. Twelve infants (2.8%) had treatment failure in the amoxicillin arm and 25 (5.9%) in the placebo arm (risk difference, 3.1; P value .04). Two infants in the placebo arm died, whereas no deaths occurred in the amoxicillin arm. Other adverse outcomes, as well as the proportions of relapse, were evenly distributed across both study arms.

Conclusions: This trial failed to show equivalence of placebo to amoxicillin in the management of isolated fast breathing without hypoxemia or other clinical signs of illness in term young infants.

Clinical trials registration: NCT01533818.

Keywords: amoxicillin; clinical trial.; fast breathing; newborn; young infants.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Figures

Figure 1.

Trial interim flowchart. Abbreviation: CHW, community health worker.