Reviewed by Rebekah Moehring, MD, MPH, FSHEA, FIDSA, Duke University, Durham, NC and Vanessa Stevens, PhD, Veteran’s Affairs Office of Quality and Patient Safety, Salt Lake City, UT
October’sissue of JAMA reported a large, Australian multicenter trial, “Selective Decontamination of the Digestive Tract in Intensive Care Patients” or SuDDICU, which aimed to evaluate the effect of selective decontamination of the digestive tract (SDD) on mortality among ventilated patients. An accompanying systematic review and meta-analysis incorporated SuDDICU data using Bayesian methods.
SuDDICU was a cluster-randomized, crossover trial performed in 19 Australian ICUs including 5982 ventilated patients. This trial was powered to evaluate in-hospital mortality, with secondary outcomes including positive blood cultures and identification of antibiotic-resistant organisms. Intervention patients received an oral paste and a gastric suspension containing colistin, tobramycin, and nystatin for the duration of ventilation plus a 4-day course of intravenous antibiotic. Group imbalances were noted: intervention patients had delayed enrollment (16h vs. 3h from ICU admission), higher exposure to oral chlorhexidine, and higher receipt of antibiotics prior. Mortality outcomes were not statistically different (753/2791 (27.0%) for SDD vs. 928/3191 (29.1%) for standard of care, odds ratio, 0.91 [95% CI, 0.82-1.02]; P = .12). Recovery of antibiotic-resistant organisms was lower in the intervention group, but so were rates of culturing. Limitations also note low rates of resistance events and relatively short period of follow up. Thus, this study does not offer definitive evidence about potential effects on resistance.
Bayesian meta-analyses are becoming increasingly popular because they can account for prior information, incorporate more sources of uncertainty, and directly estimate the probability that the treatment is better than the comparator. Data from 30 trials and >24,000 patients were analyzed to assess SDD versus standard of care on risk of in-hospital mortality among ventilated patients. The estimate of ~10% reduction in the risk of in-hospital mortality (relative risk (RR) 0.91) was similar to the point estimate from SuDDICU, which was also the 2nd largest trial included in the analysis. The posterior probability, which can be interpreted as the probability that SDD reduces in-hospital mortality, was 99.3%. Heterogeneity among studies was acceptable (I2= 33.9%). Of note, the primary outcome was described as in-hospital mortality, but only one-third (n=10) of pooled studies reported mortality at this time point. The rest (n=20) reported ICU mortality. Subgroup analysis suggested differential effects depending on use of IV (RR 0.84, 95% CrI 0.74 – 0.94) versus non-IV agents (1.01, 95% CrI 0.91 – 1.11). Reductions were observed in the risk of ICU-associated bacteremia and ventilator-associated pneumonia. Importantly, impacts on antimicrobial resistance could not be estimated due to data quality, low event rates, and sample size.
We’ve seen trial data on SDD since the 1980s and found it difficult to generalize. The 2022 updated SHEA compendium on prevention of VAP identified SDD as an “additional strategy” to be employed in select ICUs where baseline prevalence of antibiotic resistance is low and essential strategies are not enough. Caution was advised to monitor for development of resistance prospectively if implemented. Even though data quality was graded high, downsides of routine broad-spectrum antibiotics in high-risk hospitalized patients plus limited long-term follow up data to understand risks of emerging antibiotic resistance are cause for caution – like knowing a crocodile may be lurking in murky waters. It’s unlikely that SuDDICU and this meta-analysis will change this assessment in most hospitals.