Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation
Authors:   The SuDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Boschert Catherine , Broadfield Emma , Chimunda Timothy , Fletcher Jason , Knott Cameron , Porwal Sanjay , Smith Julie , Bhonagiri Deepak , Leijten Monique , Narayan Sandhya , Sanchez David , Saunders Peta , Sherriff Carli , Barrett Jonathan , Hanlon Gabrielle , Jelly-Butterworth Sarah , O'Donnell Julie , Watson Judith , Bihari Shailesh , Brown Julia , Comerford Sharon , Laver Russell , McIntyre JoAnne , Shrestha Tapaswi , Xia Jin , Bates Samantha , Fennessy Gerard , French Craig , Kootayi Sathyajith , Marshall Fiona , McEldrew Rebecca , McGain Forbes , Morgan Rebecca , Mulder John , Tippett Anna , Towns Miriam , Barker Ellie , Donovan Shelley , Ellis Katrina , Gaur Atul , Gibbons Hannah , Gregory Rebecca , Hair Eloise , Keehan Mary , Naumoff Jess , Turner Elisha , Brinkerhoff Gail , Bush Dustin , Cazzola Federica , Havill Ken , Healey Paul , Poulter Amber , Sunkara Krishna , Aneman Anders , Choit Rachel , Dobell-Brown Kelsey , Guo Kairui , Lee Jillian , Lombardo Lien , Manalil Zachariah , Miller Jennene , Rogers Jordan , Stewart Antony , Yanga Jana , Gresham Rebecca , Lowrey Julie , Masters Kristy , Whitehead Christina , Zaratan Beverly , Grigg Matthew , Harward Meg , Jones Cassie , Mackay Josephine , Meyer Jason , Saylor Emma , Venz Ellen , Walsham James , Wetzig Krista , Brown Nerissa , Chapman Marianne , Glasby Kathleen , Gluck Samuel , Murthy Tejaswini , O'Connor Stephanie , Raith Eamon , Rivett Justine , Yap Joannies , Ashelford Angela , Bass Frances , Fitzgerald Emily , Flower Oliver , Hudson Bernard , Janin Pierre , Limbrey Elizabeth , Mar Sharon , O'Connor Anne , Owen Melissa , Pallas Naomi , Pilowsky Julia , Roach Veronica , Ruse Elizabeth , Stedman Wade , Tokumitsu Miyuki , Yarad Elizabeth , Inskip Deborah , Jacques Theresa , Kintono Adeline , Milner Catherine , Sidoli Rebecca , Kurenda Catherine , Peake Sandra , Williams Patricia , Cohen Jeremy , Davie Amanda , Owens Amy , Purcell Roslyn , Venkatesh Balasubramanian , Costello Cartan , Davey-Quinn Alan , Davies Michael , Elgendy Ahmed , Geng Wenli , Jagarlamudi Veerendra , Mac Partlin Matthew , Patil Mahadev , Purdon Adam , Sterba Martin , Marshall Andrea , Delaney Anthony , Abdel-All Marwa , Clark Hayley , Espinosa Natalie , Finfer Benjamin , Hardie Miranda , Moungatonga Dijlah , Nangla Conrad , Osbourne Fiona , Schneider Tina , Shrestha Prakriti , Wilson Elizabeth , Schoeler Isabella , Armenis Manuela , Byrne Dominic , Nagarajaiah Amrutha , Velappan Prakesh , Glass Parisa , Myburgh Kate , Smith Philippa , Bachmaier Martina , Knowles Daryll , Tattersall Michael , Myburgh John A. , Seppelt Ian M. , Goodman Fiona , Billot Laurent , Correa Maryam , Davis Joshua S. , Gordon Anthony C. , Hammond Naomi E. , Iredell Jon , Li Qiang , Micallef Sharon , Miller Jennene , Mysore Jayanthi , Taylor Colman , Young Paul J. , Cuthbertson Brian H. , Finfer Simon R. 
Published: October 2022

ImportanceWhether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain.ObjectiveTo determine whether SDD reduces in-hospital mortality in critically ill adults.Design, Setting, and ParticipantsA cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021.InterventionsICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a 3-month interperiod gap. Patients in the SDD group (n = 2791) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191) received standard care.Main Outcomes and MeasuresThe primary outcome was in-hospital mortality within 90 days. There were 8 secondary outcomes, including the proportion of patients with new positive blood cultures, antibiotic-resistant organisms (AROs), and Clostridioides difficile infections. For the ecological assessment, a noninferiority margin of 2% was prespecified for 3 outcomes including new cultures of AROs.ResultsOf 5982 patients (mean age, 58.3 years; 36.8% women) enrolled from 19 ICUs, all patients completed the trial. There were 753/2791 (27.0%) and 928/3191 (29.1%) in-hospital deaths in the SDD and standard care groups, respectively (mean difference, −1.7% [95% CI, −4.8% to 1.3%]; odds ratio, 0.91 [95% CI, 0.82-1.02]; P = .12). Of 8 prespecified secondary outcomes, 6 showed no significant differences. In the SDD vs standard care groups, 23.1% vs 34.6% had new ARO cultures (absolute difference, −11.0%; 95% CI, −14.7% to −7.3%), 5.6% vs 8.1% had new positive blood cultures (absolute difference, −1.95%; 95% CI, −3.5% to −0.4%), and 0.5% vs 0.9% had new C difficile infections (absolute difference, −0.24%; 95% CI, −0.6% to 0.1%). In 8599 patients enrolled in the ecological assessment, use of SDD was not shown to be noninferior with regard to the change in the proportion of patients who developed new AROs (−3.3% vs −1.59%; mean difference, −1.71% [1-sided 97.5% CI, −∞ to 4.31%] and 0.88% vs 0.55%; mean difference, −0.32% [1-sided 97.5% CI, −∞ to 5.47%]) in the first and second periods, respectively.Conclusions and RelevanceAmong critically ill patients receiving mechanical ventilation, SDD, compared with standard care without SDD, did not significantly reduce in-hospital mortality. However, the confidence interval around the effect estimate includes a clinically important benefit.Trial RegistrationClinicalTrials.gov Identifier: NCT02389036