Probiotic, prebiotic, and synbiotic use in critically ill patients.

PURPOSE OF REVIEW: To summarize the existing data regarding the use of probiotics, prebiotics, and synbiotics in select disorders encountered in the intensive care unit setting. RECENT FINDINGS: Recent systematic reviews and meta-analyses have more rigorously aggregated the fragmented primary data which suffers from multiple limitations. SUMMARY: Probiotics are living microorganisms which, when ingested in adequate amounts, provide health benefits to the host. The mechanisms of these benefits include improved gastrointestinal barrier function, modification of the gut flora by inducing host cell antimicrobial peptides, releasing probiotic antimicrobial factors, competing for epithelial adherence, and immunomodulation to the advantage of the host. In the intensive care unit, probiotics appear to provide benefits in antibiotic-associated diarrhea, ventilator-associated pneumonia, and necrotizing enterocolitis. With increasing rates of antibiotic resistance among common nosocomial pathogens and fewer new antibiotics in the research pipeline, increasing attention has been placed on nonantibiotic approaches to the prevention and treatment of nosocomial infections. Existing studies of probiotics in critically ill patients are limited by heterogeneity in probiotic strains, dosages, duration of administration, and small sample sizes. Although probiotics are generally well tolerated and adverse events are very rare, the results of the PROPATRIA (Probiotics Prophylaxis in Patients with Predicted Severe Acute Pancreatitis) trial highlight the need for meticulous attention to safety monitoring. Better identification of the ideal characteristics of effective probiotics coupled with improved understanding of mechanisms of action will help to delineate the true beneficial effects of probiotics in various disorders.

Probiotics' effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis.

INTRODUCTION: To evaluate the efficacy of probiotics in preventing nosocomial pneumonia in critically ill patients. METHODS: We searched PubMed, EMBASE, and the Web of Science for relevant studies. Two reviewers extracted data and reviewed the quality of the studies independently. The primary outcome was the incidence of nosocomial pneumonia. Study-level data were pooled using a random-effects model when I(2) was > 50% or a fixed-effects model when I(2) was < 50%. RESULTS: Twelve randomized controlled studies with a total of 1,546 patients were considered. Pooled analysis showed a statistically significant reduction in nosocomial pneumonia rates due to probiotics (odd ratio [OR]= 0.75, 95% CI 0.57 to 0.97, P = 0.03, I(2) = 46%). However, no statistically significant difference was found between groups regarding in-hospital mortality (OR = 0.93, 95% CI 0.50 to 1.74, P = 0.82, I(2) = 51%), intensive care unit mortality (OR = 0.84, 95% CI 0.55 to 1.29, P = 0.43, I(2) = 0%), duration of stay in the hospital (mean difference [MD] in days = -0.13, 95% CI -0.93 to 0.67, P = 0.75, I(2) = 46%), or duration of stay in the intensive care units (MD = -0.72, 95% CI -1.73 to 0.29, P = 0.16, I(2) = 68%). CONCLUSIONS: The use of probiotics was associated with a statistically significant reduction in the incidence of nosocomial pneumonia in critically ill patients. However, large, well-designed, randomized, multi-center trials are needed to confirm any effects of probiotics clinical endpoints such as mortality and length of ICU and hospital stay.

Effects of Probiotics in Conditions or Infections Similar to COVID-19 on Health Outcomes: An Evidence Analysis Center Scoping Review.

Probiotics have been suggested as a potential intervention for improving outcomes, particularly ventilatory-associated pneumonia, in patients infected with coronavirus disease 2019 (COVID-19). However, with the rapid development of the COVID-19 pandemic, there is little direct evidence available in infected patients. The objective of this scoping review is to examine the availability and nature of literature describing the effect of probiotics in adults with conditions or infections similar to COVID-19 infection on related health outcomes. MEDLINE, Cumulative Index to Nursing & Allied Health Literature, and Cochrane Databases were searched for studies published from 1999 to May 1, 2020, examining the effect of probiotics in conditions applicable to individuals infected with COVID-19, including, but not limited to, other forms of coronavirus, critical illness, and mechanical ventilation. The databases search identified 1925 unique articles, 77 full-text articles were reviewed, and 48 studies were included in this scoping review, including 31 primary studies and 17 systematic reviews. Primary studies examined a range of interventions that varied by probiotic diversity and types, including 8 studies that focused on synbiotics, which include both pre- and probiotics. Several systematic reviews examined the effect of probiotics on ventilator-associated pneumonia and other infections. Although most systematic reviews concluded probiotics may improve these outcomes, most systematic review authors concluded that the evidence was low in quality and high in heterogeneity. In the absence of direct evidence with patients infected with COVID-19, studies in comparable populations are currently the best resource to guide probiotics interventions in conjunction with clinical expertise and multidisciplinary health care planning.

Effect of a Probiotic Preparation on Ventilator-Associated Pneumonia in Critically Ill Patients Admitted to the Intensive Care Unit: A Prospective Double-Blind Randomized Controlled Trial.

BACKGROUND: Ventilator-associated pneumonia (VAP) occurs as a life-threatening complication in critically ill mechanically ventilated patients. Probiotic administration may modify the gut microbiota; however, whether this modification could decrease VAP occurrence is not known. METHODS: In this study, 100 adult critically ill patients undergoing mechanical ventilation for >48 hours were randomly assigned to either the probiotic or the control group. The patients in the probiotic group received 2 capsules of probiotic preparation containing Lactobacillus, Bifidobacterium, and Streptococcus spp., and those in the control group received placebo daily for 14 days. RESULTS: The patients in the probiotic group had a lower incidence of statistically microbiologically confirmed VAP. The duration of intensive care unit (ICU) and hospital stay was also lower in the probiotic group (P < .05). More than half of the patients in the control group had gastric residuals during ICU stay, compared with only 30% of patients in the probiotic group (P = .004). Probiotic usage led to a nonsignificant decrease in diarrhea, gastric and oropharyngeal colonization, and incidence of multidrug-resistant pathogens. The Kaplan-Meier survival curves for time to the first episode of VAP did not show a significant difference between probiotic and control groups (log-rank test = 1.89; P = .17). CONCLUSIONS: The results of probiotic administration for the prevention of VAP remain inconclusive in this trial. However, such an approach can decrease the length of ICU and hospital stay. Well-designed multicenter clinical studies with defined combinations of probiotics and definite end points are necessary in this field.

Diagnosis of ventilator-associated pneumonia.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is difficult to diagnose. Recent data suggest quantitative endotracheal aspirate (ETA) may be noninferior diagnostically to quantitative bronchoalveolar lavage (BAL). We hypothesized this would be the case. METHODS: Blind quantitative ETA and BAL were performed on 150 consecutive ventilated patients with suspected VAP in a prospective single-centre medical intensive care unit study over a 2-year inclusion period. Patients were either antibiotic-naive or antibiotic-free for 72 hours. Diagnostic yield, Gram stain and culture results, and impact on antibiotic therapy were assessed. The independent impact of a positive BAL or ETA result on ventilator settings and 28-day mortality was calculated. The BAL/ETA safety was assessed hemodynamically. RESULTS: Bronchoalveolar lavage had significantly higher diagnostic yield (49.3% vs 34.0%, P = .01), more frequent impact on antibiotic therapy (usually de-escalation) (48.0% vs 32.7%, P = .01), and greater sensitivity (64.1% vs 42.6%, P = .0003) than ETA. There was moderate intertest agreement and no difference in specificity and positive and negative predictive values. A positive BAL or ETA result did not independently alter the frequency of ventilator changes or 28-day mortality. Both procedures were well tolerated. CONCLUSION: Quantitative BAL is safe and has greater diagnostic utility than ETA for VAP facilitates de-escalation. This study provides support for quantitative BAL in VAP diagnosis.