NEW YORK (Reuters Health) – Enterally administered probiotic treatment with Lactobacillus rhamnosus GG can cut the rate of ventilator-associated pneumonia (VAP) in high-risk patients, according to pilot study results.
“The mechanism(s) of action of Lactobacillus (or any probiotic) is/are not known,” lead author Dr. Lee E. Morrow told Reuters Health via email. “However, there is general agreement (and data supporting) that benefits are primarily seen through four primary avenues.”
“These include: (1) competition of probiotics with pathogens for key nutrients; (2) interactions of probiotics with the surfaces of the host organism in a manner that reduces the ability of microbes to penetrate into the host’s body; (3) probiotic secretion of various substances that create unfavorable conditions for the growth of pathogens; (4) probiotic stimulation of the host’s immune system in a manner that maintains the ability of the immune system to resist infections — so called immunomodulation.”
Dr. Morrow, at Creighton University School of Medicine in Omaha, Nebraska, and his associates chose L. rhamnosus because of its “robust safety data” and suggestions that it may have preferential activity in the upper airways
Their randomized, double-blind study included 138 adult patients likely to require mechanical ventilation for at least 72 hours. The active treatment arm received L. rhamnosus suspended in sterile, water-based surgical lubricant, applied as a slurry to the oropharynx, as well L. rhamnosus mixed in sterile water given through the nasogastric tube. Placebo treatment with inert plant starch inulin was given the same way. Treatment started within 24 hours of intubation.
Microbiologically confirmed VAP was diagnosed in 28 of 70 patients (40.0% in the placebo arm) and in 13 of 68 patients (19.1%) in the probiotics arm (p=0.007), the team reports in the American Journal of Respiratory and Critical Care Medicine, published online on June 3. They estimate a number needed to treat of approximately 5.
The active intervention also significantly reduced rates of Clostridium difficile diarrhea and the number of days of related antibiotic treatment.
Dr. Morrow’s group observed no adverse events ascribed to treatment, including cases of Lactobacillus infection.
The authors emphasize that their findings are preliminary and cannot be generalized to the general ICU population. They note that their study population was very sick (mean APACHE score ~ 23, mean duration of mechanical ventilation ~ 10 days), and that their sample size was underpowered for most end points.
They also caution that there may be the potential for iatrogenic infection, as seen in another trial, highlighting the need for scrupulous patient monitoring.
Concluding, they write, “Lactobacillus may represent a novel, inexpensive, and non-antibiotic approach to prevention of nosocomial infections in properly selected ICU patients.”
Despite their optimistic conclusion, Dr. Morrow advised that “probiotics should not be used in critically ill patients outside of a clinical trial until more rigorous and academically sound studies clearly establish safety and efficacy for each proposed indication.”
“The surprising results of the PROPATRIA study (increased mortality in pancreatitis patients treated with a novel probiotic preparation) should remind us all of the potentially disastrous outcomes when novel therapies are studied in such a fragile patient population,” he continued. “The margin for error is essentially non-existent.”
His team is now looking at the potential use of killed bacteria for VAP prevention.
“If immunomodulation is the primary mechanism of action, we could theoretically see the same benefit using dead agents — without the potential safety concerns,” Dr. Morrow said. “We are also proposing a larger, multi-center study wherein the criteria for study entry would be liberalized, thereby giving a more real-world assessment of the utility of probiotics for routine VAP prophylaxis in the ICU.”
Am J Resp Crit Care Med 2010.