By Elizabeth V. Robilotti, MD, MPH
Assistant Attending Physician, Division of Infectious Diseases, Hospital for Special Surgery, New York, NY
SYNOPSIS: Two recent articles contribute to the ongoing discussion of whether selective decontamination of the digestive tract provides a mortality benefit for patients who are receiving mechanical ventilation.
SOURCES: SuDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group; Myburgh JA, Seppelt IM, Goodman F, et al. Effect of selective decontamination of the digestive tract on hospital mortality in critically ill patients receiving mechanical ventilation: A randomized clinical trial. JAMA 2022;328:1911-1921.
Hammond NE, Myburgh J, Seppelt I, et al. Association between selective decontamination of the digestive tract and in-hospital mortality in intensive care unit patients receiving mechanical ventilation: A systematic review and meta-analysis. JAMA 2022;328:1922-1934.
Selective decontamination of the digestive tract, or SDD, involves application of topical nonabsorbable antimicrobial agents to the oropharynx and upper gastrointestinal tract of patients who are receiving mechanical ventilation to reduce ventilator-associated pneumonia (VAP). SDD often is combined with a short-term intravenous antibiotic therapy. Whether SDD has a favorable impact on mortality among patients receiving mechanical ventilation, sufficient to merit universal adoption, has been debated for decades. Two recent articles, a randomized clinical trial (RCT) and a meta-analysis, contribute to the ongoing discussion without yielding a definitive conclusion.
In the first study, SuDDICU investigators enrolled 5,982 mechanically ventilated patients in a cluster, crossover, randomized clinical trial across 19 Australian intensive care units (ICUs) from 2017 through 2021. The SDD strategy included application of an oral paste and gastric suspension composed of colistin, tobramycin, and nystatin for the duration of mechanical ventilation and administration of at least a four-day course of empiric intravenous antibiotics that included gram-negative coverage.
The primary analysis demonstrated no difference in mortality at hospital discharge between the SDD group (27%) and the standard care group (29.1%) (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.82-1.02). Adjustments for oral chlorhexidine use (a potent topical oral antiseptic), overall intravenous antibiotic exposure, and enrollment of patients with unclear anticipated duration of mechanical ventilation also did not yield significant differences.
On an individual level, microbiologic secondary outcomes showed SDD reduced recovery of new resistant organisms and new bacteremia compared to those in the standard care group. There was no observed benefit for C. difficile infections or cumulative antibiotic exposure (measured as defined daily doses over 28 days). An ecological assessment enrolled 8,599 patients at predefined timepoints (pre-trial, period 1 intervention and gap, inter-period gap and period 2, and post-trial period) was performed to account for microbiologic variation over time at participating ICUs. SDD was noninferior to standard care for development of new positive blood cultures and C. difficile infections; however, the mean difference for cultures of new antibiotic-resistant organisms did not meet the noninferiority threshold for first (-1.71 [95% CI, -7.73 to 4.31]) and second (-0.32 [95% CI, -6.12 to 5.47]) intervention periods. Antimicrobial resistance among trial sites was low, limiting the generalizability of the ecologic assessment to detect institutional changes in antimicrobial-resistant infections. Broad applicability further limited by the brief SDD period per site (12 months) left the long-term impact of universal SDD on overall institutional microbial ecology unknown.
Hammond et al completed a systematic review and a meta-analysis encompassing 32 RCTs on the association of SDD and in-hospital mortality in ICU patients receiving mechanical ventilation. Cumulatively, the meta-analysis included 24,389 patients, with 75.2% (18,335/24,389) contributed by three trials, including the contemporaneously published SuDDICU trial. Compared to standard of care, the SDD group pooled estimate of hospital mortality was 0.91 (95% credible interval, 0.82-0.99) compared to standard care group.
Subgroup analyses included mortality at the longest follow-up, incidence of VAP, and duration of mechanical ventilation, all of which did not show a benefit of SDD. No significant difference in either ICU or hospital length of stay was identified (-0.86, [95% CI, -1.73 to 0]; -0.52 [95% CI, -2.20 to 1.20]). Microbiologic secondary outcomes assessed when available included incidence of resistant organisms, C. difficile, and bacteremia; however, these data were considered to be of low certainty by the study authors.
COMMENTARY
The main concerns expressed about universal adoption of SDD as routine practice remain lack of conclusive mortality benefit for all ventilated patients and fear of SDD impact on individual and institutional microbial ecology. These concerns are compounded by logistical and staffing issues related to the acquisition and application of an appropriate nonabsorbable antimicrobial product. Unfortunately, these recent articles do not settle this decades-long debate.
Some have adjudicated the above data to be sufficient for adoption of universal SDD in settings of low antimicrobial resistance (AMR) prevalence, arguing that the majority of evidence supporting SDD is from select countries (Netherlands, Australia, and New Zealand) with relatively low AMR. Adoption in middle and high AMR-prevalent ICU settings is less clear. For regions that must do the cost benefit calculus between mortality reduction and impact on AMR, key questions remain, including optimal SDD strategy and antimicrobial components, as well as ideal target populations for the intervention.
REFERENCE
- Bonten M. Selective decontamination of the digestive tract: An answer at last? JAMA 2022;328:2310-2311.
