Selective digestive tract decontamination assessed in ventilated ICU patients

A systematic review found that mechanically ventilated ICU patients had lower in-hospital mortality rates with selective digestive tract decontamination versus standard care or placebo, while a trial found improvement in rates of positive blood cultures and antibiotic-resistant organisms, but not mortality, with the intervention.

ICU patients receiving mechanical ventilation may benefit from selective decontamination of the digestive tract (SDD), according to two recent studies.

In the first study, a systematic review and meta-analysis of randomized clinical trials, researchers evaluated whether SDD is associated with lower in-hospital mortality rates in adults receiving mechanical ventilation in ICUs versus standard care or placebo. SDD is an infection control strategy that usually involves administering nonabsorbable, topical antimicrobial agents to the oropharynx and upper GI tract, with or without short-term broad-spectrum IV antibiotics. The study's primary outcome was in-hospital mortality. Secondary outcomes included ventilator-associated pneumonia, ICU-acquired bacteremia, and incidence of positive cultures of antimicrobial-resistant organisms. Results were published Oct. 26 by JAMA.

Thirty-two randomized clinical trials involving 24,389 participants were included in the analysis. Median patient age was 54 years, and the median proportion of women was 33%. Data from 30 trials and 24,034 participants contributed to the primary outcome. The pooled estimated risk ratio (RR) for death for SDD compared with standard care was 0.91 (95% credible interval [CrI], 0.82 to 0.99; moderate certainty), with a 99.3% posterior probability that SDD reduced hospital mortality. Trials in which SDD included an IV agent showed benefit (RR, 0.84; 95% CrI, 0.74 to 0.94), while trials without an IV agent did not (RR, 1.01; 95% CrI, 0.91 to 1.11). SDD was associated with reduced risk for ventilator-associated pneumonia (RR, 0.44; 95% CrI, 0.36 to 0.54) and ICU-acquired bacteremia (RR, 0.68; 95% CrI, 0.57 to 0.81).

The authors noted that the prevalence of antibiotic resistance in the included studies was relatively low and that the evidence of an association between SDD and the secondary outcomes was of very low certainty, among other limitations. They concluded that SDD compared with standard care or placebo was associated with lower in-hospital mortality in mechanically ventilated ICU patients.

The second study, conducted by some of the same researchers and also published Oct. 26 by JAMA, was a cluster crossover trial of 5,982 mechanically ventilated adults from 19 ICUs in Australia to determine whether SDD reduced mortality. The study was performed between April 2018 and May 2021, with final follow-up in August 2021. In addition, a contemporaneous ecological assessment recruited 8,599 patients from participating ICUs between May 2017 and August 2021 to determine changes in microbiological flora.

ICUs were randomly assigned to adopt SDD or not for two alternating 12-month periods separated by a three-month gap. Every six hours for as long as they were ventilated, patients in the SDD group received an application of oral paste and administration of a gastric suspension of colistin, tobramycin, and nystatin, plus four days of an IV antibiotic, while those in the control group received standard care. The primary outcome was in-hospital mortality within 90 days. The ecological assessment had a prespecified noninferiority margin of 2% for three outcomes.

A total of 2,791 patients were assigned to the SDD group and 3,191 were assigned to the control group. All patients completed the trial. Mean age was 58.3 years, and 36.8% were women. In-hospital mortality rates were 27.0% in the SDD group and 29.1% in the standard care group (mean difference, −1.7% [95% CI, −4.8% to 1.3%]; odds ratio, 0.91 [95% CI, 0.82 to 1.02]; P=0.12). There were eight prespecified secondary outcomes, and six showed no significant differences. For those receiving SDD versus standard care, 23.1% versus 34.6% had new cultures of antibiotic-resistant organisms (absolute difference, −11.0%; 95% CI, −14.7% to −7.3%), 5.6% versus 8.1% had new positive blood cultures (absolute difference, −1.95%; 95% CI, −3.5% to −0.4%), and 0.5% versus 0.9% had new Clostridioides difficile infections (absolute difference, −0.24%; 95% CI, −0.6% to 0.1%). In the ecological assessment, SDD was not shown to be noninferior for change in the proportion of patients who developed new antibiotic-resistant organisms in the first period (−3.3% vs. −1.59%; mean difference, −1.71% [1-sided 97.5% CI, −infinity to 4.31%]) or second period (0.88% vs. 0.55%; mean difference, −0.32% [1-sided 97.5% CI, −infinity to 5.47%]).

Among other limitations, the trial was unblinded and the ecological assessment had limited power due to the overall low rate of antimicrobial resistance and the relatively short observation period, the authors said. They concluded that while SDD did not significantly improve in-hospital mortality versus standard care in mechanically ventilated patients, the confidence interval around the effect estimate included a clinically important benefit. In addition, SDD was associated with reduced positive blood cultures and cultures of antibiotic-resistant organisms and no significant increase in new C. diff infections.

“While clinicians will need to consider the primacy of the effectiveness of SDD in improving patient-centered outcomes over the effect on microbiological outcomes, the use of SDD may confer benefits in specific patient populations such as those with trauma, and further trials are needed to confirm benefits in these patients, particularly in environments with high endemic antibiotic resistance,” the authors wrote.