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Table 1 Characteristics of the study

From: Efficacy of probiotics in the prevention of VAP in critically ill ICU patients: an updated systematic review and meta-analysis of randomized control trials

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
  1. MV mechanical ventilation, CXR chest X-ray, BAL broncho alveolar lavage, PTS purulent tracheal secretion, CPIS clinical pulmonary infection score, WBC white blood cells, CFU colony forming units, T temperature, ICU intensive care unit, VAP ventilator-associated pneumonia, NGT nasogastric tube, OGT orogastric tube, TBS tracheobronchial secretions
  2. *Synbiotic 2000Forte contains 1011 CFU of P. pentoseceus 5–33:3, L. mesenteroides 32–77:1, L. paracasei ssp. 19, and L. plantarum 2362 along with inulin, betaglucan, pectin, and resistant starch as prebiotic
  3. **Medilac S contains Bacillus subtilis and Enterococcus faecalis