NASHVILLE, Tenn — Supported by several case series, a large cohort analysis has associated intensive care unit (ICU) exposure to probiotics with a measurable increase in bacteremia and bacteremia-related mortality due to the organisms in these preparations, according to new findings presented in the American College of Chest Physicians (CHEST) Annual Meeting 2022.
According to data presented by Scott Mayer, MD, chief resident at HealthONE Denver, Colorado, part of the HCA Healthcare chain of hospitals, the risk increases with any exposure to probiotics. However, the risk is particularly acute for powder formulations, presumably because dust spreads more easily to contaminate central venous catheters.
“We believe that probiotics should be completely eliminated from the ICU. Otherwise, we encourage eliminating powdered formulations,” said Mayer, who led the study.
Data linking probiotics to ICU bacteraemia were extracted from 23,533 ICU admissions over a 5-year period in the HCA hospital database. Bacteremia demonstrably related to probiotics was rare (0.37%), but the consequences were serious.
For those with probiotic-related bacteremia, the mortality rate was 25.6% or essentially twice the mortality rate of 13.5% among those without probiotic bacteremia. An odds ratio (OR) extracted from a regression analysis confirmed a significant difference (OR, 2.23; 95% CI, 1.30 – 3.71; P < .01).
“The absolute risk of mortality is modest but not negligible,” Mayer said. This suggests a probiotic-related mortality for every 200 patients taking a probiotic in the ICU.
These deaths occur without any clear compensatory benefit from taking probiotics, according to Mayer. There is a long list of potential benefits of probiotics that could be relevant to ICU patients, particularly prophylaxis for Clostridium difficile infection, but also includes a variety of gastrointestinal disorders, such as irritable bowel syndrome; however, none of these are firmly established in general, and for ICU patients in particular.
“The American College of Gastroenterology currently recommends against using probiotics for the prevention of hard Csaid Mayer. Although the American Gastroenterological Association has issued a “conditional recommendation” for the prevention of hard C infection with probiotics, Mayer noted that this is qualified by “low-quality evidence” and is not specific to the ICU setting.
“Evidence of benefit is weak or non-existent, but the risks are real,” Mayer said.
To confirm that the probiotic-associated ICU bacteremias in the HCA hospital database were, in fact, related to the probiotics patients were taking on admission, Mayer evaluated the record of each of the 86 patients with mortality. associated with bacteremia by probiotics.
“I identified the organism that grew from the blood cultures to confirm that it was contained in the probiotic the patient was taking,” explained Mayer, who said this information was available in electronic medical records.
The risk of probiotic-associated bacteremia in ICU patients was consistent with a number of case series that prompted the study. Mayer explained that she became interested when he came across patients on his ICU rounds who were taking probiotics. He knew very little about these agents and scoured the medical literature to see what evidence was available.
“I found several case reports of ICU patients with probiotic-associated infections, several of which were suspected to be associated with central line contamination,” Mayer said. In one case, the patient was not taking a probiotic but a patient in an adjacent bed was receiving an implicated probiotic powder. This led to the suspicion that the cause was contamination of the central line.
This was assessed in the HCA ICU database and was also found to be a significant risk. Among the 67 patients in whom a capsule or tablet was used, the rate of probiotic-associated bacteraemia was 0.33%. For those in which the probiotic was a powder formulation, the rate was 0.76%, a significant difference (P < .01).
Mayer acknowledged that these data do not rule out all the potential benefits of probiotics in the ICU. He believes that an obstacle to proving benefit has been the heterogeneity of available products, which are likely to be relevant to any therapeutic role, including prevention of hard C infection.
“There are now a large number of products available and they contain a wide variety of strains of organisms, so it has been a difficult area to study,” he said. However, he maintains that at this point it is prudent to avoid probiotics in the ICU because the risks are not limited to the patient making this decision.
“My concern is not just the lack of evidence of benefit relative to risk to the patient, but the potential for probiotics in the ICU to put other patients at risk,” Mayer said.
Others have also noted the potential benefits of probiotics in the ICU, but the promise remains elusive. in a 2018 review article published in the Journal of Emergency Medicine and Critical Care, the authors evaluated a series of possible applications of probiotics in critically ill patients. These included treatment of ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTIs), and surgical site infections (SSIs). For each, the data was negative or inconclusive.
Over the 4 years since the publication of the review, several trials have further explored the potential benefits of probiotics in the ICU, but have not changed this basic conclusion. for example, a Multinational test 2021 published in the lancet randomized more than 2,600 patients to probiotics or placebo and showed no effect on the incidence of VAP (21.9% vs. 21.3%).
Lead author of the 2018 review, Heather A. Vitko, PhD, an associate professor in the Department of Acute and Tertiary Care at the University of Pittsburgh, Pennsylvania, School of Nursing, also emphasized that the potential for benefit cannot be considered without the risk potential. She, like Mayer, cited case studies implicating probiotics in systemic infections.
For administration, capsules or sachets of probiotics “often need to be opened for administration through a feeding tube,” he noted. The risk of contamination comes from both air and contaminated hands, the latter of which “may cause translocation to a central line catheter where microbes have direct entry into the systemic circulation.”
He did not call for a ban on probiotics in the ICU, but recommended “a precautionary approach”, encouraging doctors to “distinguish between reality [of what has been proven] and what is presented in the commercialization of antibiotics”.
Mayer and Vitko have disclosed that they have no relevant financial relationships.