Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation

Abstract

ImportanceWhether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain.ObjectiveTo determine whether SDD reduces in-hospital mortality in critically ill adults.Design, Setting, and ParticipantsA cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021.InterventionsICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a 3-month interperiod gap. Patients in the SDD group (n = 2791) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191) received standard care.Main Outcomes and MeasuresThe primary outcome was in-hospital mortality within 90 days. There were 8 secondary outcomes, including the proportion of patients with new positive blood cultures, antibiotic-resistant organisms (AROs), and Clostridioides difficile infections. For the ecological assessment, a noninferiority margin of 2% was prespecified for 3 outcomes including new cultures of AROs.ResultsOf 5982 patients (mean age, 58.3 years; 36.8% women) enrolled from 19 ICUs, all patients completed the trial. There were 753/2791 (27.0%) and 928/3191 (29.1%) in-hospital deaths in the SDD and standard care groups, respectively (mean difference, −1.7% [95% CI, −4.8% to 1.3%]; odds ratio, 0.91 [95% CI, 0.82-1.02]; P = .12). Of 8 prespecified secondary outcomes, 6 showed no significant differences. In the SDD vs standard care groups, 23.1% vs 34.6% had new ARO cultures (absolute difference, −11.0%; 95% CI, −14.7% to −7.3%), 5.6% vs 8.1% had new positive blood cultures (absolute difference, −1.95%; 95% CI, −3.5% to −0.4%), and 0.5% vs 0.9% had new C difficile infections (absolute difference, −0.24%; 95% CI, −0.6% to 0.1%). In 8599 patients enrolled in the ecological assessment, use of SDD was not shown to be noninferior with regard to the change in the proportion of patients who developed new AROs (−3.3% vs −1.59%; mean difference, −1.71% [1-sided 97.5% CI, −∞ to 4.31%] and 0.88% vs 0.55%; mean difference, −0.32% [1-sided 97.5% CI, −∞ to 5.47%]) in the first and second periods, respectively.Conclusions and RelevanceAmong critically ill patients receiving mechanical ventilation, SDD, compared with standard care without SDD, did not significantly reduce in-hospital mortality. However, the confidence interval around the effect estimate includes a clinically important benefit.Trial RegistrationClinicalTrials.gov Identifier: NCT02389036

Staphylococcus aureus hitchhiking from colonization to bacteremia via Candida within ICU infection prevention studies: a proof of concept modelling

“…In studies where the SDD regimen containing topical polymyxin and tobramycin combined with amphotericin as the anti-fungal [10,11], prevention effects were observed. By contrast, prevention effects were not observed in the largest studies to date, where the SDD intervention contained the same TAP regimen in combination with nystatin [12,13]. The effect of concurrency could account for the striking difference in apparent prevention effects, being seemingly strong within studies of SDD and SOD using concurrent control groups, [18] which rely on an trauma ICU setting (trauma50), mean or median length of ICU stay ≥ 7 days (los7), exposure to a topical anti-septic (a_S), exposure to TAP (tap), concurrency of a control group with an antibiotic-based intervention group (CC), exposure to a non-decontamination based prevention method (non-D), greater than 90% use of mechanical ventilation (mvp90) or exposure to PPAP (ppap).…”

“…The circles contain error terms. The three part boxes represent the binomial proportion data for Candida and Staphylococcus VAP (v_can_n, v_sr_n) and candidemia (b_can_n) or bacteremia (b_sr_n) counts with the number of patients as the denominator which is logit transformed using the logit link function in the generalized model untested assumption that the concurrency effect is negligible, versus being either less evident or not observed within studies using non-concurrent control groups, [10,12,13,37]. Rebound colonization on TAP withdrawal is also a difficult to quantify ecological effect [8,38,39].…”

“…Moreover, from the first SDD/SOD study [9], TAP use within the ICU context was presumed to induce contextual effects mediated via the ICU microbiome with potential to spill over into concurrent control group patients. Several SDD studies deliberately avoided these contextual effects by using either nonconcurrent or no control group patients in the study [10][11][12][13].…”

Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19

“…The oral microbiota is altered in COVID-19 patients [ 28 , 29 ] and has been proposed as a potential reservoir of pulmonary co-infections, as well as contributing to a disturbed gut microbiota with potential for microbial translocation to the systemic circulation [ 10 ]. Studies of selective decontamination of the oral cavity and upper GI tract have shown promise in reducing in-hospital mortality in ICU patients receiving mechanical ventilation [ 30 , 31 ]. Our data, in light of the overall literature [ 10 ], suggest that such strategies could also be relevant in future intervention trials of critical COVID-19 patients.…”

Role of Selective Digestive Decontamination in the Prevention of Ventilator-Associated Pneumonia in COVID-19 Patients: A Pre-Post Observational Study

“…Therefore, in April 2021, we decided to introduce in our protocol the use of selective digestive tract decontamination (SDD). The use of SDD for reducing the VAP was proposed more than 30 years ago [ 7 , 8 ] but it is still sporadically used worldwide even though several trials indicated reasonable evidence of benefit without detrimental effects on bacterial resistance selection [ 9 , 10 ]. In COVID-19 patients, some studies investigated the effects of SDD in preventing secondary infections with promising results [ 11 , 12 , 13 ].…”