Table 1: Summary of design and risk of bias in randomized controlled trials of probiotics in the prevention of diarrhea associated with Clostridium difficile
Author, yearDefinition of diarrheaMethod for detecting C. difficileSample sizeProbiotic dosage,CFUs × 109*Treatment durationLength of follow-upRisk of bias†Industry funded‡
Ouwehand et al.,24 2014 3 stools Bristol scale 7GDH and toxin A EIA; toxin B by cell culturePro-2 168
Pro-1 168
Pla 167
LA, LPl, B (capsule; L pro-1 4.7, pro-2 17)Duration of antibiotic treatment + 7 d4 wk (post antibiotic treatment)AYes
Allen et al.,10 2013 3 stools Bristol scale 5-7, or looser than normal by patient report, in 24 hIn-house tissue culture assay + EIA for toxins or ELFA for toxins or GDH and toxin A EIAPro 1493
Pla 1488
LA, B (capsule; all 60)21 d8 wk total for AAD/ 12 wk for CDADANo
Selinger et al.,25 2013 3 stools Bristol scale 6-7ELFA for toxins or GDH and toxin A EIAPro 112
Pla 117
LA, LPl, LPa, LD, B, ST (powder; all 450)Duration of antibiotic treatment + 7 d4 wk (post pro/pla treatment)BYes
Gao et al.,20 2010 3 liquid stools in 24 hTriage panel (not specified) and toxin B by cell culturePro-2 86
Pro-1:85
Pla 84
LA, LC (capsule; pro-1 L 50, pro-2 L 100)Duration of antibiotic treatment + 5 d21 dAYes
Sampalis et al.,26 2010 1 episodes unformed or liquid stool in 24 hToxin A and B (not specified)Pro 216
Pla 221
LA, LC (milk; L 50)Duration of antibiotic treatment + 5 d21 dCYes
Safdar et al.,27 2008§Watery or liquid stools for  2 consecutive daysToxin (not specified)Pro 23
Pla 17
LA (capsule; L 20)Pro 22.8 (9.4) d, pla 24.5 (4.8) dNRBNo
Beausoleil et al.,28 2007 3 liquid stools in 24 hCytotoxin assay (not specified)Pro 44
Pla 45
LA and LC (milk; L 50)Duration of antibiotic treatment21 dCYes
Hickson et al.,29 2007 2 liquid stools daily in excess of normal for  2 dToxin (not specified)Pro 69
Pla 66
LC, LB, ST (yogourt; L 0.1, 0.01, O 0.1)Duration of antibiotic treatment + 7 d28 dANo
Plummer et al.,30 2004¶NALatex agglutination or EIA for toxinsPro 69
Pla 69
LA, B (capsule, total 20)20 dNRCYes
Heimburger et al.,31 1994> 200 g stool in 24 hCulture and titresPro 16
Pla 18
LA, LB (granules, dosage not given) 5 d5 dCNo

Note: AAD = antibiotic-associated diarrhea, B = Bifidobacterium, CDAD = Clostridium-difficile-associated diarrhea, CFUs = colony-forming units, EIA = enzyme immunoassay, ELFA = enzyme-linked fluorescent assay, GDH = glutamate dehydrogenase, L = Lactobacillus spp., LA = L. acidophilus, LB = L. bulgaricus, LC = L. casei, LD = L. delbrueckii subsp. bulgaricus, LPa = L. paracasei, LPl = L. plantarum, NA = not available, NR = not reported, Pla = placebo, Pro = probiotics, ST = Streptococcus thermophilus.

*Dosage is given in colony-forming units unless specified otherwise. Where 2 figures are given, the first represents the total dosage of Lactobacillus species (L), and the second the dosage of other species (O).

†A = no major sources of bias, B = 1 possible source of bias, C = 2 possible sources of bias.

‡Included direct study sponsorship. We did not consider supply of investigational material without conditions or support for activities not associated with the study as support from the manufacturer.

§Treatment duration is given as mean and standard deviation. Although follow-up was mentioned as part of the study design, the precise duration was not reported.

Follow-up was post discharge, but no details were given as to treatment duration post intervention or post discharge.