Background
Mechanical ventilation is a life-saving intervention frequently required for critically ill patients in intensive care units (ICUs). However, ventilated patients are at high risk of infections, particularly ventilator-associated pneumonia (VAP) and bloodstream infections, leading to increased morbidity, length of stay, and mortality. One strategy proposed to reduce infection risk is selective decontamination of the digestive tract (SDD), which involves the application of topical non-absorbable antibiotics to the oropharynx and gastrointestinal tract, combined with a brief course of intravenous antibiotics.
While some prior studies suggested that SDD might reduce infections and mortality, concerns persist regarding whether it alters the ICU microbial ecology unfavorably, leading to antibiotic-resistant organisms. Previous regional analyses, including data from Australia, failed to demonstrate a mortality benefit, necessitating comprehensive international data to clarify the clinical effectiveness and safety of SDD in mechanically ventilated ICU patients.
Study Design
The recent landmark trial led by the SuDDICU Investigators was a large, pragmatic, cluster-randomized, crossover trial conducted in 26 ICUs across Australia and Canada. The study enrolled nearly 9,300 patients who required mechanical ventilation and randomized ICUs to either implement SDD or continue with standard care over two 12-month periods.
Patients allocated to the SDD group received oral and gastric antimicrobial interventions throughout the duration of mechanical ventilation, alongside intravenous antibiotics administered for the first four days after enrollment. The standard care group received routine management without targeted decontamination. Additionally, over 10,700 other patients in the participating ICUs were followed observationally to assess overall ecosystem impact.
The primary endpoint was all-cause in-hospital mortality at 90 days. Secondary endpoints included ICU mortality, duration alive and free of mechanical ventilation, ICU stay, and hospital stay. Microbiological outcomes assessed the incidence of new bloodstream infections and the emergence of antibiotic-resistant organisms. The ecological impact on resistance patterns was evaluated for noninferiority against a predefined margin of 2 percentage points.
Key Findings
The trial enrolled a total of 9,289 patients in the randomized component and evaluated 20,000 patients overall, including ecological surveillance.
Mortality: At 90 days, mortality was 27.9% (1,175/4,215) in the SDD group versus 29.5% (1,494/5,065) in the standard care group, yielding an odds ratio (OR) of 0.93 (95% confidence interval [CI], 0.84 to 1.05; P = 0.27), indicating no statistically significant reduction in mortality with SDD.
Bloodstream Infections: New bloodstream infections were less frequent in the SDD group at 4.9% versus 6.8% in standard care, with an adjusted mean difference of –1.30 percentage points (95% CI, –2.55 to –0.05), suggesting a modest but significant reduction in infections.
Antibiotic-Resistant Organisms: Antibiotic-resistant organisms were cultured in 16.8% of SDD patients versus 26.8% in standard care, an adjusted mean difference of –9.60 percentage points (95% CI, –12.40 to –6.80), indicating a lower incidence of resistant organisms with SDD in the randomized trial.
Ecologic Assessment: However, in the broader ecological assessment including all ICU patients, the noninferiority criterion for SDD regarding the development of new antibiotic-resistant organisms was not met. This raises caution about potential negative effects on ICU microbial ecology over time.
Safety: Adverse events potentially related to SDD were rare, occurring in 0.3% of SDD patients, with no such events in standard care. Serious adverse event rates were comparable between groups (1.1% vs. 1.2%).
Expert Commentary
This extensive and rigorously conducted trial provides important clarity on the clinical role of SDD in critical care. Although SDD did not confer a statistically significant survival benefit, the reduction in bloodstream infections and antibiotic-resistant organisms within the treated patients is notable and may translate to clinical advantages in select settings.
Yet, the failure to establish ecological noninferiority highlights concerns that widespread use of SDD might alter microbial populations negatively at the institutional level, potentially fostering resistant strains indirectly. This ecological safety concern is crucial for stewardship and infection control policies.
Some limitations include the cluster-randomized design which may be vulnerable to ecological fallacy and variation in ICU practices across countries. Also, the short-term intravenous antibiotic component of SDD complicates attribution solely to topical decontamination.
Current guidelines remain divided on SDD implementation, and this trial reinforces the importance of balancing potential patient-level benefits with population-level risks.
Conclusion
In mechanically ventilated ICU patients, selective decontamination of the digestive tract does not reduce overall in-hospital mortality but does modestly decrease bloodstream infections and antibiotic-resistant organisms among treated patients. However, concerns regarding microbial ecology in ICU populations suggest cautious and judicious use of SDD is warranted. Future research should focus on optimizing protocols to maximize benefits while safeguarding antimicrobial resistance at the institutional level.
Funding and Registration
This study was funded by the National Health and Medical Research Council of Australia and the Canadian Institutes of Health Research. The trial is registered under ClinicalTrials.gov number NCT02389036.
References
- SuDDICU Investigators for the Australia and New Zealand Intensive Care Society Clinical Trials Group and the Canadian Critical Care Trials Group; Cuthbertson BH, Billot L, Campbell MK, Daneman N, Davis JS, et al. Selective Decontamination of the Digestive Tract during Ventilation in the ICU. N Engl J Med. 2025 Oct 29. doi: 10.1056/NEJMoa2506398. Epub ahead of print. PMID: 41159880.