Early Oral Antibiotic Switch in Staphylococcus aureus Bacteraemia: The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Early Oral Switch Protocol
Authors: de Kretser Dana , Mora Jocelyn , Bloomfield Max , Campbell Anita , Cheng Matthew P , Guy Stephen , Hensgens Marjolein , Kalimuddin Shirin , Lee Todd C , Legg Amy , Mahar Robert K , Marks Michael , Marsh Julie , McGlothin Anna , Morpeth Susan C , Sud Archana , Ten Oever Jaap , Yahav Dafna , Bonten Marc , Bowen Asha C , Daneman Nick , van Hal Sebastiaan J , Heriot George S , Lewis Roger J , Lye David C , McQuilten Zoe , Paterson David L , Owen Robinson J , Roberts Jason A , Scarborough Matthew , Webb Steve A , Whiteway Lynda , Tong Steven Y C , Davis Joshua S , Walls Genevieve , Goodman Anna L ,   the SNAP Early Oral Switch Domain-Specific Working Group and SNAP Global Trial Steering Committee, Marsh J , Tong S Y C , Davis J S , Goodman A L , Walls G , Morpeth S C , Hensgens M , Mora J , Yahav D , McGlothlin A , Cheng M P ,   for the SNAP Trial Group, Anagnostou Nick , Acrhuleta Sophia , Athan Eugene , Barina Lauren , Best Emma , Brett Katie , Burden Hannah , Daley Peter , Davies Jane , Partha De P , Dishon-Benattar Yael , Flanagan Katie , Grant Jennifer , Gregson Dan , Grimwade Kate , Hatcher James , Henderson Andrew , Jankovic Dina , Johnstone Jennie , Russel Lee I , Chew Ka Lip , Llewelyn Martin , Martson Anne-Grete , McArthur Colin , McNeil Diana , Metcalf Sarah , Nourse Clare , O’Sullivan Matthew , Petrella Lina , Pett Sarah , Rogers Benjamin A , Sim James , Soares Marta O , Stone Neil , Tilley Robert , Turner Rebecca , Tutone Viliame , Underwood Jonathan , Voss Lesley , Webb Rachel H , Wilson Heather , Wuerz Terence 
Published: November 2023

Abstract

Background
Staphylococcus aureus bloodstream infection (bacteremia) is traditionally treated with at least 2 weeks of intravenous (IV) antibiotics in adults, 3–7 days in children, and often longer for those with complicated disease. The current practice of treating S. aureus bacteremia (SAB) with prolonged IV antibiotics (rather than oral antibiotics) is based on historical observational research and expert opinion. Prolonged IV antibiotic therapy has significant disadvantages for patients and healthcare systems, and there is growing interest in whether a switch to oral antibiotics following an initial period of IV therapy is a safe alternative for clinically stable patients.

Protocol
The early oral switch (EOS) domain of the S. aureus Network Adaptive Platform (SNAP) trial will assess early switch to oral antibiotics compared with continued IV treatment in clinically stable patients with SAB. The primary endpoint is 90-day all-cause mortality. Hospitalised SAB patients are assessed at platform day 7 ±2 (uncomplicated SAB) and day 14 ±2 (complicated SAB) to determine their eligibility for randomization to EOS (intervention) or continued IV treatment (current standard of care).

Discussion
Recruitment is occurring in the EOS domain of the SNAP trial. As of August 2023, 21% of all SNAP participants had been randomized to the EOS domain, a total of 264 participants across 77 centers, with an aim to recruit at least 1000 participants. We describe challenges and facilitators to enrolment in this domain to aid those planning similar trials.