Probiotics for the Prevention and Treatment of Clostridium difficile in Older Patients

Jasmin Islam; Jonathan Cohen; Chakravarthi Rajkumar; Martin J. Llewelyn


Age Ageing. 2012;41(6):706-711. 

In This Article

Primary Prevention

Multiple published studies describe the use of probiotics to prevent AAD and two relevant meta-analyses have been performed. D'Souza et al. identified nine placebo-controlled studies, seven in adults and two in children with a total of 1,214 subjects; four using S.-boulardii, four Lactobacillus species preparations and one strain of Enterococcus species. All but one study of S. boulardii indicated a protective effect and the combined odds ratio in favour of active treatment was 0.37 [95% confidence interval (CI) 0.26–0.53].[29] Sazawal et al. identified 18 studies describing the prevention of AAD and one, the prevention of CDI specifically. The largest study included in the earlier meta-analysis was excluded because it was written in French but 10 studies published after 2001 were included. All showed a positive effect and the authors concluded that probiotics significantly reduce AAD by 52% (95% CI: 35–65%).[30] Both analyses suggested a bias away from the publication of negative results, but Sazawal et al. estimated that 330 unpublished negative trials would have to exist to overturn their findings. Nevertheless, both meta-analyses should be interpreted with caution given the inconsistency in study design between trials including the definition of AAD, duration of follow-up, the age of patients recruited and the type and number of probiotic strains used.

Since 2006, there have been 10 randomised controlled trials investigating the role of probiotics in the prevention of AAD, with seven suggesting a benefit.[31–37] In a small Swedish study, patients in the active group experienced fewer gastrointestinal symptoms including loose watery stool (odds ratio: 0.69; 95% CI: 0.52–0.92) and nausea (odds ratio: 0.51; 95% CI: 0.30–0.85) compared with the placebo group, although there was no difference in AAD.[38] The remaining studies were methodologically flawed, lacking an appropriate matched placebo, inadequate dosing of the active product and limited follow-up.[39,40]

There have been fewer studies specifically addressing the effect of probiotics on CDI which is usually measured as a secondary outcome (Table 1). In a study by Hickson et al., 135 patients were randomised to receive a probiotic (Lactobacillus casei DN-114001, Lactobacillus bulgaricus and Streptococcus thermophilus) or placebo milkshake drink twice daily for the duration of antibiotic use and the following 7 days. An absolute risk reduction of 17% (7–27%) occurred with no cases of CDI in the probiotic group. However, this study only recruited 8% of the total screened population due to stringent exclusion criteria, suggesting these results may not be applicable to the wider hospital community.[32] Recently, the first dose-response effect study was conducted at a single centre in China. Patients were randomised to two probiotic capsules containing Lactobacillus acidophilus CL1285® and Lactobacillus casei LBC80R® (Pro-2), single probiotic capsule and placebo capsule (Pro-1) or two placebo capsules. The incidence of CDI was lowest in the Pro-2 group (1.2%) with higher rates seen in the Pro-1 (9.4%) and placebo groups (23.8%). The overall rates of CDI were greater in this study compared with those in Europe and North America; possibly reflecting the exclusive inclusion of patients receiving antibiotics associated with an increased risk of CDI.[31]