Chapter 2: Severe Infections

Section 2.1: Selective Digestive Decontamination: Insights from the SuDD-ICU Trial

ICU-acquired infections remain one of the leading causes of mortality in critically ill patients. As early as 1984, researchers proposed the use of non-absorbable antibiotics for selective digestive decontamination (SDD) to reduce microbial colonization, thereby preventing ventilator-associated pneumonia and bloodstream infections, and reducing mortality in critically ill patients. Since 1984, this field has accumulated a substantial body of peer-reviewed literature, including randomized controlled trials conducted in ICUs and meta-analyses, sparking multiple rounds of public debate both in support of and against the practice. Yet, to this day, its global clinical application remains limited.

I. Benefits and Risks of Selective Digestive Decontamination
The longstanding debate over whether SDD should be used in critically ill patients has centered on two core issues: (1) whether there is definitive evidence that SDD reduces overall mortality in critically ill patients, and (2) whether the risk of antimicrobial resistance from broad antibiotic use outweighs its potential benefits.

Beyond these factors, another major barrier to the widespread clinical adoption of SDD is the lack of high-quality evidence regarding its impact on antimicrobial resistance, coupled with profound concerns about its potential to drive antibiotic resistance. These fundamental concerns, combined with inconsistent mortality outcomes and cost-effectiveness considerations, have contributed to persistently low clinical adoption rates.

Multiple studies (2007–2023, encompassing 65 RCTs and 11 meta-analyses) have confirmed that SDD significantly reduces the incidence of ICU-acquired bloodstream infections and ventilator-associated pneumonia. However, evidence regarding its impact on overall mortality remains highly inconsistent. The 2022 JAMA publication of the SuDDICU trial provided pivotal new evidence. This large, rigorously designed cluster-cross-over RCT was conducted across 19 ICUs in Australia and New Zealand, enrolling 2,791 patients receiving SDD and 3,191 patients receiving standard care. The primary endpoint, in-hospital mortality, was 27.0% in the SDD group versus 29.1% in the standard care group. The odds ratio for mortality was 0.91, corresponding to a 1.7% reduction in mortality (95% CI −4.8% to +1.3%). Although the difference did not reach statistical significance, the confidence interval suggests a potential clinical benefit. A subsequent meta-analysis by Hammond et al., which incorporated these new findings, pooled 32 randomized clinical trials (24,389 patients total). The pooled relative risk for mortality with SDD versus standard care was 0.91 (95% CI 0.82–0.99), with a Bayesian posterior probability of 99.3%, indicating a 95% probability that SDD reduces in-hospital mortality by 1% to 18%. Notably, mortality benefits were only observed when the SDD protocol included intravenous antibiotic administration. The SuDDICU trial was originally planned for four countries but primarily enrolled data from Australia and Canada (low-resistance environments). Given the low endemic antimicrobial resistance in the study setting and the failure to demonstrate a statistically significant mortality benefit, the generalizability and clinical guidance value of these findings in high-resistance settings remain limited.

II. Insights from the SuDDICU Research Update
In October 2025, the SuDDICU Research Group published the final integrated results, including data from Canadian sites, in the New England Journal of Medicine. The Canadian cohort employed the identical protocol and standardized investigational preparations as the Australian SuDDICU trial. Between 2019 and 2023, seven Canadian ICU centers enrolled an additional 3,307 patients, thereby expanding the overall dataset.

The results revealed a complex landscape: while microbiological and infection control metrics improved, no significant survival benefit was observed. Regarding the primary endpoint, SDD did not significantly reduce 90-day in-hospital mortality: 27.9% (1,175/4,215) in the SDD group versus 29.5% (1,494/5,065) in the standard care group (OR=0.94, 95% CI 0.84–1.05, P=0.27). However, SDD demonstrated clear benefits in key microbiological secondary endpoints: the incidence of new bloodstream infections was 4.9% in the SDD group, significantly lower than the 6.8% in the control group. The proportion of newly cultured antibiotic-resistant bacteria was 16.8% versus 26.8%, and the incidence of new C. difficile infections was 0.7% versus 1.2%. Prespecified subgroup analyses based on age, sex, geographic region, trauma status, and disease severity revealed no differential mortality effects. However, a post hoc exploratory analysis suggested a potential survival benefit in patients with acute brain injury (OR=0.80, 95% CI 0.68–0.94).

The ecological evaluation aimed to assess the non-inferiority of SDD regarding ICU-level microbiological impact. Results indicated that for incident bloodstream infections and C. difficile infections, SDD was non-inferior to standard care. However, for the key endpoint of “new antibiotic-resistant bacterial isolates,” SDD failed to meet the predefined non-inferiority margin. The upper limit of the confidence interval (4.82) exceeded the 2-percentage-point non-inferiority threshold, meaning that an increased risk of ICU-level antimicrobial resistance with SDD cannot be ruled out. Regarding safety, the SDD group experienced a higher rate of intervention-related adverse drug reactions, though the incidence of serious adverse events was comparable between groups.

The SuDDICU study was an international multicenter RCT employing a cluster-randomized, cross-over design, alongside a concurrent observational ecological assessment. Addressing the controversies surrounding SDD application, its objective was to determine whether implementing SDD in mechanically ventilated patients reduces mortality and affects ICU microbial ecology. Each participating ICU served as the randomization unit, rather than individual patients. ICUs were randomized into two groups: one implementing the SDD protocol, and the other continuing standard care, each for 12 months. After a 3-month washout period, interventions were swapped for the next 12-month cycle. ICU randomization was stratified by bed count. The SDD protocol utilized topical agents (colistin, tobramycin, and nystatin) combined with intravenous antibiotics (third-generation cephalosporin or ciprofloxacin) for 4 days, continued until mechanical ventilation cessation or day 90. The study enrolled 20,000 patients, of whom 9,289 mechanically ventilated patients were included in the RCT per-protocol analysis. Concurrently, 10,711 ICU patients not randomized were observationally studied to assess SDD’s impact on microbial ecology. The primary endpoint was all-cause in-hospital mortality within 90 days post-randomization; secondary endpoints included ICU mortality, ventilator-free/hospital-free days, and microbiological indicators (new bloodstream infections, new resistant bacterial isolates, and C. difficileinfections).

The core conclusion is that in a broad population of critically ill, mechanically ventilated patients, routine SDD effectively reduces specific infection types but does not lower 90-day in-hospital mortality. This highlights a critical clinical reality: microbiological benefits do not invariably translate into survival advantages. Key strengths of the study include its large scale, international multicenter pragmatic design ensuring generalizability to real-world ICU settings, the use of commercially standardized preparations ensuring intervention reproducibility, and enrollment of a high-risk population with a baseline mortality of 29.5%. Major limitations include: (1) the 10-year study duration allowed for evolution in standard critical care practices, potentially diluting the intervention effect, and the open-label nature of the intervention (despite high compliance); (2) limited statistical power in the ecological evaluation to detect long-term antimicrobial resistance risks; and (3) the findings, derived from low-resistance environments, may not be generalizable to regions with high endemic antimicrobial resistance. The SuDDICU investigators emphasized that while this single trial did not demonstrate a mortality benefit, its incorporation into the latest meta-analysis suggests a high probability that SDD reduces mortality. Furthermore, exploratory subgroup analyses hinted at greater potential benefits in specific high-risk populations such as those with acute brain injury, pointing directions for future research.

III. Summary and Outlook
The SuDDICU trial provides unprecedented high-level evidence regarding the clinical value and risks of selective digestive decontamination (SDD), yet it deliberately avoids a simplistic, blanket recommendation. Instead, it elevates clinical decision-making to a more nuanced level: clinicians, hospital administrators, and policymakers must carefully balance the immediate, well-documented benefits of SDD in reducing bloodstream infections and bacterial colonization against its potential, albeit not yet fully quantified, long-term risks to the ICU microbial ecology and antimicrobial resistance landscape. This decision is highly contingent upon an institution’s specific antimicrobial resistance epidemiology, infection control infrastructure, and capacity to identify targeted high-risk patient populations. Future research should prioritize validating SDD’s clinical benefits in specific subgroups (e.g., patients with acute brain injury, severe burns, severe enteric-source infections, or profound immunodeficiency) and rigorously assess its safety and efficacy in settings with high endemic antimicrobial resistance.

In conclusion, routine implementation of SDD should not be recommended for all critically ill patients receiving mechanical ventilation. However, for defined high-risk populations, potential benefits exist, and its use may be considered following a careful risk-benefit assessment. Conducting comparable studies in high-resistance environments remains essential to evaluate the risk-benefit profile of SDD across diverse microbiological ecosystems. Furthermore, it is critical to emphasize that topical SDD regimens must exclusively utilize non-systemically absorbed antibiotics, such as colistin, tobramycin, and nystatin.
(Xie Hui; First People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Chen Dechang; Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine)

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