Session : Pediatric Infections and Immunology

171 - Short-course Antimicrobial Therapy for Paediatric Respiratory Infections (SAFER): a multicentre, Randomized, Controlled, Blinded, Noninferiority Trial

Oral Abstract

Location: On Demand

Background: Community-acquired pneumonia (CAP) is a common occurrence in childhood; consequently, evidence-based recommendations for its treatment are required. The study objective was to determine if, in previously healthy children presenting to the emergency department (ED), 5 days of high-dose amoxicillin led to noninferior rates of clinical cure at 14-21 days post-enrolment compared with 10 days of high-dose amoxicillin.

Methods: The SAFER study was a multicentre, randomized, parallel-group, multiple-blinded, controlled, noninferiority study, enrolling between 2012-2014 (single centre pilot) and then 2016-2019 (follow-up main study). Children aged 6 months – 10 years with all of the following were eligible: fever within 48h; a respiratory symptom/sign; a chest radiograph consistent with pneumonia as per the emergency MD; and a primary diagnosis of CAP. Children were excluded if they required hospitalization, had any medical comorbidities, or if they were already receiving beta-lactam antibiotic therapy. The intervention of interest was 5 days of high-dose amoxicillin followed by 5 days placebo. The control (standard care) arm received 5 days of high-dose amoxicillin followed by a different formulation of 5 days of high-dose amoxicillin. The primary outcome was clinical cure at 14-21 days post-enrolment. The pre-set noninferiority margin was 0.075 less than the clinical cure risk difference (1-sided 97.5% CI).

Results: Of the 281 participants, 119 (42%) were female; the median age was 2.6 y (25-75%ile 1.6-4.9 y). There were 140 randomized to short-course treatment and 141 to standard care. Clinical cure at 14-21 days was observed in 108/126 (86%) in the short-course arm and in 106/126 (84%) in the standard-care arm (risk difference 0.023, lower limit of 1-sided 97.5%CI -0.061). There were no participants who, after finishing amoxicillin, later deteriorated and required hospitalization for progressive CAP.

Conclusion: Short-course antibiotic therapy was noninferior to standard care for the treatment of previously healthy children with non-severe CAP diagnosed in Canadian EDs. Clinical practice guidelines should recommend no more than 5 days of amoxicillin for paediatric pneumonia management, in accordance with antimicrobial stewardship principles.

Presenting Author(s)

Jeffrey Pernica, MD, MSc, FRCPC, DTMH

Head, Division of Infectious Disease
Department of Pediatrics, McMaster University
Hamilton, ON, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Slides Slides and Audio

Co-Author(s)

SH

Stuart Harman, MD, FRCPC

Assistant Professor
University of Ottawa
Ottawa, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
AK

April J. Kam, MD MScPH FRCPC

Associate Professor
McMaster University
Hamilton, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
RC

Redjana Carciumaru, MSc

Research Coordinator
McMaster University
Hamilton, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
TV

Thuva Vanniyasingam, PhD

Biostatistician
The Research Institute of St Joe's Hamilton
Hamilton, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
TC

Tyrus Crawford, B.Soc.Sc.

Research Coordinator
Children's Hospital of Eastern Ontario Research Institute
Ottawa, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DD

Dale Dalgleish, RN, BHScN, RN, BHScN

Research Assistant
CHEO
Manotick, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SK

Sarah Khan, MD, MSc, FRCPC

Assistant Professor, Associate Medical Director Infection Prevention and Control
McMaster University, Hamilton, Ontario, Canada
Hamilton, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MF

Martha Fulford, MD FRCPC

Associate Professor
McMaster University
Hamilton, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CM

Cheryl L. Main, MD, FRCPC

Medical Microbiologist and Infectious Disease physician
Hamilton Health Sciences and Hamilton Regional Laboratory Medicine Program
Hamilton, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
RS

Robert Slinger, MD

Pediatric Infectious Diseases Specialist
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MS

Marek Smieja, MD PhD FRCPC

Professor
McMaster University
Hamilton, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
LT

Lehana Thabane, PhD

Associate Department Chair, Professor
McMaster University
Hamilton, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
ML

Mark Loeb, FRCPC, MD

ID Physician
McMaster University, Hamilton, ON
Hamilton, Ontario, Canada

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.