'Digestive Tract Decontamination Fails to Cut Deaths in Intubated ICU Patients'

 

• Selective decontamination of the digestive tract (SDD) did not lower in-hospital deaths among patients undergoing mechanical ventilation.
• At 90 days, 27.9% of patients who underwent SDD died before they were discharged from the hospital, compared with 29.5% of patients who had standard care.
• Secondary analyses showed lower rates of new bloodstream infections with the SDD approach.

Using antibiotics to decontaminate the digestive tracts of mechanically ventilated patients in the intensive care unit (ICU) wasn't significantly better than standard care at preventing in-hospital deaths, according to an international trial of more than 9,000 patients.

At 90 days, 27.9% of patients who underwent selective decontamination of the digestive tract (SDD) died before they were discharged from the hospital, compared with 29.5% of patients who had standard care only (OR 0.94, 95% CI 0.84-1.05, P=0.27), reported John Myburgh, MBBCh, PhD, of the George Institute for Global Health in Sydney, and colleagues in the New England Journal of Medicine.

Despite the mortality outcomes, "there is strong evidence that SDD, particularly when used as a combination of intravenous and topical antibiotics, is associated with improved patient-centered outcomes in mechanically ventilated patients in the ICU," Myburgh told MedPage Today.

"While the overall result for the primary patient-centered outcome -- death in hospital -- did not reach statistical significance, the direction and magnitude of the point estimate includes a clinically important difference that represents a number needed to treat of 50 patients to prevent one death," Myburgh suggested.

The findings were also presented at the annual congress of the European Society of Intensive Care Medicine in Munich.

SDD uses oral and intravenous antibiotics during mechanical ventilation to prevent hospital-acquired lower respiratory tract infections from upper gastrointestinal tract bacteria and yeasts. Although it has shown a consistent benefit in reducing mortality in numerous studies, concerns about potential development of SDD-associated antibiotic resistance has kept adoption low.

There were some trends toward better outcomes with SDD compared with standard care among the study's secondary clinical outcomes, but with the study's statistical design none of those differences were significant. Deaths in the ICU occurred in 22% of the 4,223-patient SDD group compared with 24.2% of the 5,066-patient standard-care group. Median days alive and free of ICU admission were 59.3 in the SDD group and 56.9 in those receiving standard care.

In a concurrent observational study assessing patients' microbial ecology, 4.9% of SDD patients developed new bloodstream infections compared with 6.8% of standard-care patients (adjusted mean difference -1.30 percentage points, 95% CI -2.55 to -0.05).

New antibiotic-resistant organisms were cultured in 16.8% of SDD patients and 26.8% of standard-care patients (adjusted mean difference -9.60 percentage points, 95% CI -12.40 to -6.80). An ecological assessment was unable to confirm noninferiority with SDD for new antibiotic-resistant organisms, but SDD was noninferior with regard to new bloodstream and Clostridioides difficile infections.

The two groups saw virtually no difference in median defined daily dose of antibiotics over 28 days, at 12 days in the SDD group and 11.8 days in the standard-care group.

Those microbial results counter a substantial concern among clinicians about SDD, Myburgh said.

"The SuDDICU trial confirms that the use of SDD is not associated with the development of new hospital-acquired infections and antibiotic resistance," he noted. "This is an important result because of the long-held and largely unsubstantiated concerns that the use of SDD would increase these outcomes."

The Selective Decontamination of the Digestive Tract in Intensive Care Unit (SuDDICU) trial used a crossover, cluster-randomized design in which 19 ICUs in Australia and seven ICUs in Canada were randomly assigned to use either SDD or standard care during two alternating 12-month periods. Patients crossed over to the other treatment group after a 3-month gap between the periods. The study also included an observational study from baseline to the trial's end to assess changes to patients' microbial ecology.

Eligible patients were receiving mechanical ventilation via an endotracheal tube on ICU admission or received mechanical ventilation during ICU admission. The study's Australian trial enrolled patients from 2017 through 2022, while the Canadian trial was conducted from 2019 through 2023.

There were 9,289 patients enrolled in the trial. Mean age was about 58 years, and 36% were female; median APACHE II score was 20.0 and the median MODS score was 5.0.

SDD patients received topical oral antibiotic paste applied to the oropharynx and buccal mucosa, as well as an antibiotic suspension delivered to the upper gastrointestinal tract by tube. The group also received a 4-day course of intravenous antibiotics.

The study's primary outcome was all-cause in-hospital death within 90 days after enrollment during the initial hospital admission. In a post hoc subgroup analysis, investigators observed lower mortality in the SDD group among patients with acute brain injuries (OR 0.80, 95% CI 0.68-0.94).

SDD has shown a consistent benefit signal in mechanically ventilated patients with acute brain injuries, such as traumatic brain injury, stroke syndromes, and encephalopathy, Myburgh told MedPage Today. Based on the SuDDICU results, a large pragmatic, randomized clinical trial is underway in Australia to assess the effect of preventive antibiotics in such patients.

Study limitations included the use of a nonblinded intervention. The ecological assessment's relative lack of power and short observation period allowed the researchers limited ability to confirm or refute SDD's noninferiority. The overall low incidence of antibiotic-resistant infections may make the study's results not generalizable to areas with greater antibiotic resistance rates.

Disclosures

The National Health and Medical Research Council of Australia and the Canadian Institutes of Health Research supported the study.

Myburgh had no relevant conflicts. Colleagues disclosed relationships with AM Pharma, AstraZeneca, Baxter, Matisse Pharmaceuticals, Health Research Council of New Zealand, Unity Health Toronto, University of Toronto, and Partner Therapeutics.

Primary Source

New England Journal of Medicine

Source Reference: Cuthbertson BH, et al "Selective decontamination of the digestive tract during ventilation in the ICU" N Engl J Med 2025; DOI: 10.1056/NEJMoa2506398.

https://www.medpagetoday.com/criticalcare/generalcriticalcare/118323