Does Adjunctive Clindamycin Have a Role in Staphylococcus aureus Bacteremia? A Protocol for the Adjunctive Treatment Domain of the Staphylococcus aureus Network Adaptive Platform (SNAP) Randomized Controlled Trial
Year: 2024
Type: article
Study design: Study Protocol
Abstract: BACKGROUND: The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and it is recommended in many guidelines, but this is based on limited evidence. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leukocidins (eg, Panton-Valentine leukocidin, toxic shock syndrome toxin 1, exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question. METHODS AND ANALYSIS: The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multicenter adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality rates. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either 5 days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard-of-care antibiotics. Most participants with SAB (within 72 hours of index blood culture and with no contraindications) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol, and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and Panton-Valentine leukocidin-positive isolate.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciae289
Authors: Keerthi Anpalagan, Ravindra Dotel, Derek R MacFadden, Simon Smith, Lesley Voss, Neta Petersiel, Michael Marks, Julie Marsh, Robert K Mahar, Anna McGlothlin, Todd C Lee, Anna Goodman, Susan Morpeth, Joshua S Davis, Steven Y C Tong, Asha C Bowen, the Adjunctive Clindamycin Domain-Specific Working Group for the Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Group, Keerthi Anpalagan, Ravindra Dotel, Derek R MacFadden, Simon Smith, Lesley Voss, Neta Petersiel, Michael Marks, Joshua S Davis, Asha C Bowen, Marc Bonten, Asha C Bowen, Nick Daneman, Sebastiaan J van Hal, George S Heriot, Roger J Lewis, David C Lye, Zoe McQuilten, David L Paterson, J Owen Robinson, Jason A Roberts, Matthew Scarborough, Steve A Webb, Lynda Whiteway, Genevieve Walls, Todd C Lee, Dafna Yahav, Marjolein Hensgens, Matthew P Cheng, Susan Morpeth, Steven Y C Tong, Joshua S Davis
Institutions: The Kids Research Institute Australia, The University of Western Australia, Blacktown & Mount Druitt Hospital, Westmead Hospital, University of Ottawa, Ottawa Hospital Research Institute, Cairns Hospital, Starship Children's Health, The Royal Melbourne Hospital, The University of Melbourne, Peter Doherty Institute, University College Hospital, London School of Hygiene & Tropical Medicine, Hospital for Tropical Diseases, University College London, Murdoch Children's Research Institute, Berry Consultants, LLC (United States), McGill University, Guy's and St Thomas' NHS Foundation Trust, Medical Research Council, Middlemore Hospital, John Hunter Hospital, Menzies School of Health Research, University of Newcastle Australia, Princess Margaret Hospital for Children, Perth Children's Hospital
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,001
Funders: McGill University, McGill University Health Centre, National Institute for Health and Care Research, Department of Health and Social Care, University of Oxford, Monash University, Murdoch University, ZonMw, Universiteit Utrecht, University of Toronto, Universitair Medisch Centrum Utrecht, Medical Research Council Canada, Université de Montpellier, Fiona Stanley Hospital, Starship Foundation, National Institutes of Health, Metro North Hospital and Health Service, Canadian Institutes of Health Research, Medical Research Council, National Health and Medical Research Council, National Medical Research Council, Health Research Council of New Zealand, Lee Kong Chian School of Medicine, Nanyang Technological University, National Institute of Allergy and Infectious Diseases, Institute of Infection and Immunity
Awards: G1270426774, G1677556024, Staphylococcus aureus Network Adaptive Platform (SNAP) Trial, G2271994619, G2339531072, G4231845750, G4767190930, G5521966596, SNAP-PY: Staphylococcus aureus Network Adaptive Platform trial for Paediatrics and Youth, G5895291598, Syndromic infections, G6215216097, The Staphylococcus aureus Network Adaptive Platform Trial, Clinical Impact of the Cefazolin Inoculum Effect
OpenAlex ID: W4399102732