A Sunnybrook-led study – the world’s largest and longest clinical trial in critical care – has shown a significant reduction in hospital-acquired infection in critically-ill patients on mechanical ventilation (assisted breathing) when given antibiotics preventatively, before a new infection can develop.
“While the evidence supporting the preventative use of antibiotics is strong, many health-care professionals around the world don’t use this approach, out of a concern of the effects of antibiotic resistance. But we now have irrefutable evidence, gathered from over 26 intensive care units (ICU’s) across Australia and Canada, that point to the benefits for their use,” says Dr. Brian Cuthbertson, international principal investigator of the trial, a critical care physician and a senior scientist in the Evaluative Clinical Sciences and Tory Trauma Research Programs at Sunnybrook Health Sciences Centre.
Presented at the European Society of Intensive Care Medicine on October 29, 2025 and published in the New England Journal of Medicine, the study results showed that while the use of preventative antibiotics in an ICU did not reduce hospital mortality compared to standard care, their use was associated with a clinically and statistically significant reduction in the development of new blood stream infection.
Led by Sunnybrook Research Institute in Canada and the U.K., and by the George Institute in Australia, the large randomized controlled trial and international research collaboration recruited over 20,000 participants over a 10-year period from 2009 to 2023 – over 9,200 of which were enrolled into the randomised trial.
Using selective decontamination of the digestive tract (SDD) – a preventative strategy consisting of the application of non-absorbable oral antibiotics to parts of the mouth, tongue, tonsils, throat, and stomach, combined with a short course of intravenous (IV) antibiotics – the researchers sought out to test:
- whether using antibiotics to prevent infections acquired in the hospital increases the number of patients who get better and go home after being critically unwell, and
- whether using antibiotics in this way affects patterns of antibiotic resistance – when antibiotics are no longer effective – in the ICU.
“The results came as a bit of a surprise,” says Dr. Cuthbertson, also a professor in the Department of Anesthesiology and Pain Medicine at University of Toronto’s Temerty Faculty of Medicine. “Not only did infection rates drop in this population, but the use of antibiotics did not cause antibiotic resistance, as we would have thought they would have.”
Critically-ill patients in an ICU are particularly at risk for hospital-acquired infections – infections that can develop while patients are in hospital receiving care, and are a major cause of illness, sometimes death, and increases to the costs of care.
“This research aims to give health-care professionals and patients data on the benefits so they can make informed decisions about providing preventive antibiotics as part of care,” adds Dr. Cuthbertson.