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.

Autor:	Anpalagan K; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia.; School of Medicine, University of Western Australia, Perth, Western Australia, Australia., Dotel R; Department of Infectious Diseases, Blacktown Hospital, Westmead, New South Wales, Australia.; Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, New South Wales, Australia., MacFadden DR; Faculty of Medicine, University of Ottawa, Canada, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., Smith S; Department of Infectious Disease, Cairns Hospital, Cairns, Queensland, Australia., Voss L; Starship's Children Health, Te Toka Tumai Auckland, New Zealand., Petersiel N; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia., Marks M; Clinical Research Department, London School of Hygiene & Tropical Medicine, London, United Kingdom.; Hospital for Tropical Diseases, University College London Hospital, London, United Kingdom.; Division of Infection and Immunity, University College London, London, United Kingdom., Marsh J; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia., Mahar RK; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia.; Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia., McGlothlin A; Berry Consultants, Austin, Texas, USA., Lee TC; Clinical Practice Assessment Unit and Division of Infectious Diseases, McGill University, Montreal, Quebec, Canada., Goodman A; Medical Research Council Clinical Trials Unit, Department of Infectious Diseases, University College London, Guy's and St Thomas' Foundation NHS Trust, London, United Kingdom., Morpeth S; Middlemore Hospital, Auckland, New Zealand., Davis JS; Global and Tropical Health, Menzies School of Health Research, Darwin, Northern Territory, Australia.; The Immunology and Infectious Diseases Unit, John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia.; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia., Tong SYC; Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia., Bowen AC; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia.; School of Medicine, University of Western Australia, Perth, Western Australia, Australia.; Global and Tropical Health, Menzies School of Health Research, Darwin, Northern Territory, Australia.; Department of Infectious Diseases, Perth Children's Hospital, Perth, Western Australia, Australia.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Sep 26; Vol. 79 (3), pp. 626-634.
DOI:	10.1093/cid/ciae289
Abstrakt:	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. Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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