Table 1: Evidence summary of probiotic use in critically ill adult patients with pneumonia.
Study | # of subjects | Study design | Strain of probiotic used | Patient population | Results |
Zeng, et al. [17] |
235 |
Prospective, open-label, randomized, controlled, multicenter |
Bacillus subtilis 4.5 × 109/0.25 g and Enterococcus faecalis 0.5 × 109/0.25 g. |
Medical, surgical, trauma, and neurologic critical care patients expected to be on mechanical ventilation for 48 hours or longer |
• 43 patients in the probiotic group vs. 59 in control diagnosed with microbiologically confirmed VAP (36.4% vs. 50.4%; p = 0.031) • No significant difference in clinically diagnosed VAP between groups (40.7% vs. 53%; p = 0.059) • Patients who received probiotics had a greater probability of not developing VAP (p = 0.004) • The use of probiotics resulted in a reduction of 0.28 in risk ratio for VAP (95% CI 0.03-0.47) with number needed to treat of 7 patients to prevent one case of VAP • Patients in the probiotic group experienced longer time to onset of VAP (10.4 vs. 7.5 days; p = 0.022) • No significant difference between the probiotic and control groups in eradication of PPMO colonization (46.9% vs. 32.1%; p = 0.245) or acquisition of PPMO colonization (44.2% vs. 52.8%; p = 0.254) • Probiotics did not affect the gastric colonization of PPMOs (27.8% vs. 19.2%; p = 0.756) • No significant difference in duration of mechanical ventilation, duration of antibiotics for VAP, number of antibiotic-free days, days in the ICU, days in the hospital after ICU admission, ICU mortality, or in-hospital mortality • No adverse events reported with probiotic use |
Barraud, et al. [18] |
167 |
Double-blind, randomized, placebo controlled |
2 × 1010 Lactobacillus rhamnosus GG, Lactobacillus casei, Lactobacillus acidophilus, and Bifidobacterium bifidum). |
Mechanically ventilated patients in a medical ICU expected to be intubated for at least 2 days |
• No significant difference in 28-day mortality (25.3% probiotic vs. 23.7% placebo; p = 0.80) or mortality at 90 days (31% vs. 30%; p = 0.90) • Probiotics did not affect ICU or hospital length of stay or organ failure reversal. • Decreased incidence of catheter-related bloodstream infections in the probiotic group (1.84 vs. 6.78 catheter-days; p = 0.005) • Less patients with catheter-related bloodstream infections in the probiotic group (3.4% vs. 13.7%; p = 0.005) • No difference in urinary tract infections, VAP, or combined ICU-acquired infections • Probiotic use did not affect colonization with multi-drug resistant bacteria • Subgroup analysis: reduction in 28-day mortality in patients with severe sepsis who received probiotics (odds ratio 0.38; 95% CI 0.16-0.93; p = 0.035) • No adverse effects were observed |
Morrow, et al. [19] |
146 |
Prospective, randomized, double-blind, placebo controlled |
Lactobacillus rhamnosus GG |
Mechanically ventilated patients at high risk for developing VAP |
• Less VAP in probiotic group (19.1% vs. 40%; p = 0.007) • Patients who received probiotics received less days of antibiotics for VAP (5.6 vs. 8.6; p = 0.05) and Clostridium difficile associated diarrhea (0.5 vs. 2.1; p = 0.02) • Less Clostridium difficile associated diarrhea in probiotic group (5.8% vs. 18.6%; p = 0.02) • Similar duration of diarrhea between groups • No significant differences in mortality, duration of mechanical ventilation, hospital and ICU length of stay, or hospital charges between the two groups |
Knight, et al. [20] |
259 |
Prospective, randomized, placebo controlled |
Synbiotic 2000 FORTE: Pediococcus pentosaceus, Leuconostoc mesenteroides, Lactobacillus paracasei (1010 bacteria per sachet) and betaglucan, inulin, pectin, and resistant starch (prebiotics) |
Enterally fed patients requiring mechanical ventilation for 48 hours or more |
• VAP incidence similar in the synbiotic and placebo groups (9% vs. 13%; p = 0.42) • No significant differences in ventilator days, VAP episodes/1000 ventilator days, length of ICU stay, ICU or hospital mortality were observed between groups • The use of synbiotics did not affect the microbial species or colonization rates of potential pathogens • No adverse effects were reported |
Forestier, et al. [21] |
208 |
Prospective, randomized, double blind, placebo-controlled |
Lactobacillus casei rhamnosus |
Patients 18 years or older with an ICU stay longer than 48 hours and a nasogastric feeding tube |
• Six patients in the placebo group acquired gastric P. aeruginosa (3 ceftazidime-resistant isolates). • Three patients in the probiotic group acquired gastric P. aeruginosa (1 ceftazidime-resistant isolate). • No statistically significant differences between the two arms in the delay in gastric acquisition of P. aeruginosa. • Thirteen positive samples of P. aeruginosa was detected in respiratory tract specimens (5 ceftazidime-resistant isolates) of subjects in the placebo arm. • Five positive samples of P. aeruginosa was detected in respiratory tract specimens (all ceftazidime-sensitive) of subjects in the probiotic arm. • A statistically significant difference between two arms was seen in acquisition delay of P. aeruginosa in the respiratory tract (p < 0.05). • P. aeruginosa caused VAP in 8 patients in the placebo arm and 3 patients in the probiotic arm (no statistically significant difference). • Seventeen patients in placebo arm and 6 patients in the probiotic arm either had gastric or respiratory tract P. aeruginosa growth (p = 0.02). |
Shinotsuka, et al. [22] |
49 |
Prospective, controlled, randomized, open-labeled |
Probiotic: Lactobacillus johnsonii La1 Prebiotic: Soybean polysaccharide |
Patients on mechanical ventilation admitted to the ICU |
• The proportion of enterobacteria growth in the tracheal secretion of subjects in the pre- and probiotic groups was not statistically significant. • There was non-significant decrease in bacterial isolation and increase in negative samples of gastric secretions on the 7th day in the pre, pro, and symbiotic groups compared to placebo. • There was no statistically significant difference between study groups in rates of nosocomial infections and VAP. |
Klarin, et al. [23] |
50 |
Prospective, randomized, active-controlled |
Lactobacillus plantarum 299 |
Critically ill patients 18 years or older with an anticipated need for mechanical ventilation for at least 24 hours |
• Eight patients in the probiotic arm and 13 patients in the chlorhexidine arm grew pathogenic bacteria in their oropharyngeal samples (p = 0.13) |