Table 1 Characteristics of the study
Study | Design/duration | Participants | Intervention | Outcome | Definition of VAP |
|---|---|---|---|---|---|
Barraud et al. [19] | Double-blind/until weaning | Adults intubated on MV > 2 days n = 167 SOFA score in probiotics: 9 ± 4.6 and control: 9.7 ± 4.8 | Probiotic: enterally administered once a day pro-biotics Ergyphilus capsule (multispecies Lactobacillus rhamnosus GG, L. casei, L. acidophilus, and Bifidobacterium bifidum) 2 × 1010 CFU/d Control: Placebo Started soon after admission, continued during entire period of mechanical ventilation but not more than 28 days | Primary endpoint: 28-day mortality Secondary endpoints: 90-day mortality, the reversal of organ failure, the occurrence of ICU-acquired infections, colonization by day 28, and ICU length of stay | 1. CXR + [1 sign: (1) PTS, (2) Temp ≥ 38.3 °C, (3) WBC ≥ 10,000/mm3] 2. Positive quantitative cultures from BAL |
Giamarellos-Bourboulis et al. [20] | Double-blind/28 days | Multiorgan injuries; tracheal intubation; MV n = 72 APACHE II, GCS score in probiotic group: 19.36, 7.64, and control group: 19.36, 7.80 | Probiotic: Synbiotic 2000 Forte*; 1011CFU/d by NGT/gastrostomy for 15 days Control: Placebo Started on admission to the ICU | Analyzed the microbiological and laboratory findings of patients | All of the following: (1) CXR, (2) PTS, (3) CPIS > 6 |
Knight et al. [17] | Double blind/28 days | Critically ill patients on ventilator; MV > 48 h n = 300 APACHE II score in probiotic: 17 (12-23) and control: 17 (12-22) | Probiotic: Synbiotic 2000 Forte; 1010CFU/d twice daily by NGT/OGT for 28 days/death/discharge Control: Placebo Started within 24 h of admission to ICU | Primary outcome: incidence of VAP Secondary outcome variables: oropharyngeal flora, ventilator days, and VAP rates per 1000 ventilator days, ICU length of stay, ICU mortality, and hospital mortality | CXR + 2 sign: (1) T ≥ 38.0 °C, (2) WBC ≥ 12,000/mm3 or ≤ 4000/mm3, (3) PTS |
Kotzampassi et al. [21] | Double blind, 15 days | Severe multiple organ failure; adults; MV ≥ 48 h; life expectancy > 15 days n = 77 APACHE II, GCS score in probiotic group: 19.36, 7.64, and control group: 19.36, 7.80 | Probiotic: Synbiotic 2000 Forte*; 1011CFU/d by NGT/gastrostomy Control: Placebo (powdered glucose polymer) Started at time of ICU admission given for 15 days | Primary endpoints: systemic infection rate during ICU stay, or the development of SIRS and MODS Secondary endpoints: Mortality, length of stay in the ICU, and number of days under mechanical ventilation | All of the following: (1) CXR, (2) PTS, (3) T ≥ 38.5 °C, (4) WBC > 12,000/mm3 or < 4000/mm3, (5) positive quantitative cultures from BAL |
Mahmoodpoor et al. [22] | Double blind, 2 weeks | Critically ill adults, in ICU, MV > 48 h APACHE II score in probiotic: 24.1 ± 6.2; control: 22.8 ± 4.7 | Probiotic: 1 capsule in 12 h, 1010 bacteria × 14 days (Lactobacillus species (casei, acidophilus, rhamnosus, bulgaricus), Bifidobacterium species (breve, longum), Streptococcus thermophilus administered using feeding tube; not with gavage formula) Control: Placebo (sterile maize starch powder) | Primary outcome: VAP occurrence Secondary outcomes: ICU and hospital length of stay, duration of mechanical ventilation, and complications during the study | CXR + 2 sign: (1) T ≥ 38.0 °C or ≤ 36.0 °C, (2) leukocytosis or leucopenia, (3) purulent sputum underwent BAL |
Morrow et al. [7] | Double blind, not stated | Adults requiring MV > 72 h n = 146 APACHE II score in probiotic group: 22.7 ± 7.5, control: 23.7 ± 8 | Probiotic: L. rhamnosus GG 2 × 109 CFU/d twice daily; NGT or OGT Control: placebo Started within 24 of admission until extubated/tracheostomy placement/death | Primary outcome: Microbiologically confirmed VAP Secondary outcome: mortality; time to occurrence of VAP; durations of MV, ICU stay, and hospital stay; Clostridium difficile–associated diarrhea; other ICU-associated diarrhea; antibiotic consumption (total, VAP-specific, and C. difficile-specific); and hospital charges | CXR + 2 sign: (1) T ≥ 38.5 °C or ≤ 35.0 °C, (2) WBC ≥ 10,000/mm3 or ≤ 3000/mm3, (3) PTS |
Shimizu et al. [18] | Single blind/4 week | Adults; diagnosed sepsis; on MV APACHE II score in probiotic: 19 (14-24) and control: 20 (14-26) | Probiotic: Yakult BL Seichoyaku (contains 6 × 108 CFU of B. breve and L. casei with galactooligosaccharides as prebiotic) NGT daily control: Placebo doses Started within 3 days of admission | Primary outcome: infectious complications such as enteritis, ventilator-associated pneumonia (VAP), and bacteremia Secondary outcomes: mortality, fecal bacterial counts, and organic acid concentration | Pneumonia after 48-72 h of MV |
Tan et al. [23] | Single blind/28 day | Closed head injury, adult, patients with severe TBI and Glasgow Coma Scale scores between 5 and 8 n = 52 | Probiotic group: Golden Bifid containing 0.5 × 108 Bifidobacterium longum, 0.5 × 107 Lactobacillus bulgaricus and 0.5 × 107 Streptococcus thermophilus. Started within 48 h of ICU admission for 21 days | VAP rate, duration of ICU stay, duration of antibiotics use, and 28-day mortality rate | CXR + 2 sign: (1) T > 38.0 °C or < 35.5 °C, (2) WBC > 12,000/mm3 or < 4000/mm3, (3) PTS, (4) positive semiquantitative cultures of TBS |
Zeng et al. [16] | Open label/14 day | Critically ill adults with MV > 48 h n = 250 APACHE II score in probiotic: 14.7 ± 3.9; control: 16.6 ± 3.3 | Probiotic group: Probiotic capsule (Medilac-S**) 0.5 g (1.5 × 1010) three times/day by NGT Control group: Placebo Started within 24 h of admission to the ICU given for 14 days | Primary endpoints: incidence of microbiologically confirmed VAP, proportions of eradication of colonization and acquired colonization with PPMOs in the oropharynx and stomach Secondary endpoints: duration of MV, duration of ICU stay, duration of hospital stay, mortality (in ICU, in-hospital) and number of days of antibiotic use for VAP | CXR + 2 sign: (1) T > 38.0 °C or < 35.5 °C, (2) WBC > 12,000/mm3 or < 3000/mm3 (3) TBS |