Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis

Figures & data

Figure 1 CONSORT diagram of the study selection process.

Abbreviations: RCT, randomized control trial; CONSORT, Consolidated Standards of Reporting Trials.

Table 1 Characteristics of all published randomized control trials evaluating the use of probiotics for the prevention of CDAD (1966–2015)

Study	Total number of patients (numbers on probiotics, numbers on placebo)	Age of patients (adults versus pediatrics)	Health care setting (inpatient versus outpatient)	Probiotic used	Age (years), (mean ± SD)
Surawicz et al (I989)^Citation49	180 (116; 64)	Adults	Inpatient	Saccharomyces boulardii	Probiotic: 48.6 Placebo: 45.4
McFarland et al (I995)^Citation48	193 (97; 96)	Adults	Inpatient	Saccharomyces boulardii	Probiotic: 40.7±16.0 Placebo: 42.3±17.7
Arvola et al (I999)^Citation50	119 (61; 58)	Children	Mix	Lactobacillus GG	Probiotic: 4.7 (range: 2 weeks–11.8 years) Placebo: 4.4 (range: 2 weeks–12.8 years)
Thomas et al (2001)^Citation44	267(133; 134)	Adults	Inpatient	Lactobacillus GG	Probiotic: 57.2±18.0 Placebo: 54.4± 17.4
Plummer et al (2004)^Citation51	138 (69; 69)	Adults	Inpatient	Lactobacillus acidophilus, Bifidobacterium bifidum	Patients > 18 years
Duman et al (2005)^Citation42	376(196; 180)	Adults	Outpatient	Saccharomyces boulardii	Probiotic: 45.68±12.7 Placebo: 44.65±13.9
Kotowska et al (2005)^Citation52	246(119; 127)	Children	Mix	Saccharomyces boulardii	Probiotic: 39.3±29 months Placebo: 39.3±41 months
Can et al (2006)^Citation53	151 (73; 78)	Adults	Inpatient	Saccharomyces boulardii	Range: 25–50
Beausoleil et al (2007)^Citation45	89 (44; 45)	Adults	Inpatient	Lactobacillus acidophilus CLI285 and Lactobacillus casei	Probiotic: 68.8±14.5 Placebo: 72.9±13.4
Cindoruk et al (2007)^Citation46	124 (62; 62)	Adults	Outpatient	Saccharomyces boulardii	Probiotic: 45.82±13.35 Placebo: 47.56±13.53
Hickson et al (2007)^Citation54	113 (57; 56)	Adults	Inpatient	Lactobacillus casei imunitass, Lactobacillus bulgaricus, Streptococcus thermophilus	All patients: 74
Rafiq et al (2007)^Citation55	100 (45; 55)	Adults	Inpatient	Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium bifidum, Streptococcus thermophilus	Patients > 18
Miller et al (2008; a)^Citation56	189 (95; 94)	Adults	Inpatient	Lactobacillus GG	Patients > 18
Miller et al (2008; b)^Citation56	316(157; 159)	Adults	Inpatient	Lactobacillus GG	Patients > 18
Ruszczynski et al (2008)^Citation57	240(120; 120)	Children	Mix	Lactobacillus rhamnosus	Probiotic: 18.6±13.7 months Placebo: 32.6±41 months
Safdar et al (2008)^Citation58	40 (23; 17)	Adults	Inpatient	Lactobacillus acidophilus	Probiotic: 66.56±14.53 Placebo: 72.47±11
Wenus et al (2008)^Citation59	63 (34; 29)	Adults	Inpatient	Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5, Bifidobacterium Bb-12	Probiotic: 58.8±16.5 Placebo: 56.2±18.7
Gao et al (2010)^Citation60	255 (171; 84)	Adults	Inpatient	Lactobacillus acidophilus CLI285 and Lactobacillus casei LBC80R	Probiotic: 60±6 Placebo: 60±6
Lonnermark et al (2010)^Citation47	163 (80; 83)	Adults	Mix	Lactobacillus plantarum	Probiotic: median =47 Placebo: median =43
Sampalis et al (2010)^Citation61	437 (216; 221)	Adults	Mix	Lactobacillus acidophilus CLI285, Lactobacillus casei	Probiotic: 59.5±18.1 Placebo: 58.1±19.1
Pozzoni et al (2012)^Citation62	204 (106; 98)	Adults	Inpatient	Saccharomyces boulardii	Probiotic: 79.9±9.9 Placebo: 78.5±9.7
Allen et al (2013)^Citation19	2,941 (1,470; 1,471)	Adults	Inpatient	Lactobacillus acidophilus, Bifidobacterium bifidum, Bifidobacterium lactis	Probiotic: median (IQR) =77.2 (70.8–83.6) Placebo: median (IQR) =77.0 (71.3–83.5)
Selingeret al (2013)^Citation63	122(61; 61)	Adults	Inpatient	Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii bulgaricus, Streptococcus thermophilus	Probiotic: 57.9 Placebo: 57.0
Shan et al (2013)^Citation20	283 (139; 144)	Children	Inpatient	Saccharomyces boulardii	Probiotic: 49.8±36 months Placebo: 48.7±34 months
Wong et al (2014)^Citation21	158 (76; 82)	Adults	Inpatient	Lactobacillus casei	Probiotic: 52.5 Placebo: 51
Ouwehand et al (2014)^Citation22	450 (304; 146)	Adults	Inpatient	Lactobacillus acidophilus, Lactobacillus paracasei, Bifidobacterium lactis Bi-07, Bifidobacterium lactis Bi-04	Probiotic high dose: 50.5±11.0 Probiotic low dose: 49.3±11.4 Placebo: 50.0±11.0

Abbreviations: CDAD, Clostridium difficile-associated diarrhea; GG, Gorbach/Goldin (a strain of Lactobacillus rhamnosus isolated by Dr Sherwood Gorbach and Dr Barry Goldin); IQR, interquartile range; SD, standard deviation.

Figure 2 Forest plot evaluating the RR of CDAD associated with probiotic use.

Abbreviations: RR, relative risk; CI, confidence interval; CDAD, Clostridium difficile-associated diarrhea.

Figure 3 Forest plot evaluating the RR of CDAD associated with various species of probiotic use.

Abbreviations: RR, relative risk; CI, confidence interval; CDAD, Clostridium difficile-associated diarrhea.

Figure 4 Forest plot evaluating the RR of CDAD associated with probiotic use in adult and pediatric populations.

Abbreviations: RR, relative risk; CI, confidence interval; CDAD, Clostridium difficile-associated diarrhea.

Figure 5 Forest plot evaluating the RR of CDAD associated with probiotic use in both inpatient and outpatient populations.

Abbreviations: RR, relative risk; CI, confidence interval; CDAD, Clostridium difficile-associated diarrhea.

Figure 6 Funnel plot assessing publication bias (analyzing the effect of probiotic supplementation on the incidence of CDAD).

Abbreviation: CDAD, Clostridium difficile-associated diarrhea.

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