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Infectious Diseases in Clinical Practice:
doi: 10.1097/IPC.0b013e3182a1eec1
Editorial Comment

Probiotics for Recurrent Clostridium difficile Infection in Solid Organ Transplant Recipients

Bose, Diptiman D. PhD, MS

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From the Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA.

Correspondence to: Diptiman Bose, PhD, MS, Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, 1215 Wilbraham Rd, Springfield, MA 01119. E-mail: diptiman.bose@wne.edu.

The author has no conflicts of interest to declare.

Transplant recipients on immunosuppressive therapy have a weakened immune system and therefore are at a greater risk for Clostridium difficile infection (CDI) and recurrence.1 Approximately 1 in 3 transplant recipients will develop symptomatic CDI, and a third of those can develop recurrence.2 The risk factors for recurrence are varied and can depend on the type of transplantation, immunotherapy, and concurrent antibiotics. The management of the first CDI recurrence includes treatment used during the initial CDI episode and a pulsed or tapered vancomycin for the second CDI recurrence.3 Probiotics have been under investigation as adjunctive therapy for the treatment of recurrent CDI; however, the studies demonstrating the use and efficacy of probiotics remain inconclusive and controversial. Although the exact mechanism of action is unclear, it is hypothesized that probiotics might help prevent CDI recurrence by reducing the risk of colonization by pathogenic bacteria. However, there is limited evidence to support the use of probiotics as treatment to decrease CDI recurrence. Two randomized controlled trials that used Lactobacillus rhamnosus GG did not show any benefit for the treatment of recurrent CDI.4,5 A 2008 Cochrane analysis that assessed the effectiveness of probiotics for the treatment of CDI concluded that there was a lack of evidence to recommend probiotics as adjunct therapy.6 However, a 2013 Cochrane analysis that assessed the effectiveness of probiotics in preventing CDI in participants taking antibiotics reported that when probiotics are given with antibiotics they reduce the risk of developing CDI by 64%.7 More studies are therefore needed to bolster evidence for the use of probiotics for recurrent CDI. In a retrospective study conducted by Deshpande et al,8 published in the current issue, 2 high-risk populations of solid organ transplant patients with recurrent CDI were treated with or without Lactobacillus. They concluded that the administration of Lactobacillus was associated with a decreased rate of relapse in 1 of the 2 transplant recipient patient groups. The administration of probiotics was concluded to be safe with no reported bacteremia. More importantly, the use of probiotics was associated with a significant decrease in C. difficile recurrence in lung transplants. However, a similar decrease in CDI was not observed in liver recipients. A few other studies have shown that other probiotics, particularly Saccharomyces boulardii, can shorten the duration of CDI diarrhea and/or decrease relapse rates in patients with CDI. However, the current study has limitations, and the results should be interpreted with caution. First, the Lactobacillus preparations were heterogeneous, and the duration of therapy was uncertain. Second, although various reasons for differences in the CDI recurrence between the lung and liver transplant recipients were hypothesized, no clear underlying cause was identified. Although the authors report no incidence of bacteremia, the use of live microorganisms in immunosuppressed individuals should be carried out with extreme caution. There are a few reported cases of probiotic-induced bacteremia/fungemia in patients with central venous catheters and the elderly.9 With no clear guidelines on the type, dosage, and duration of probiotics, more studies are needed to help understand the role of probiotic therapy in CDI recurrence. However, the current findings of a reduction in CDI recurrences for the Lactobacillus group overall and its safety profile in the solid organ transplant recipients suggest that probiotics may be beneficial in preventing CDI recurrences.

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REFERENCES

1. Boutros M, Al-Shaibi M, Chan G, et al. Clostridium difficile colitis: increasing incidence, risk factors, and outcomes in solid organ transplant recipients. Transplantation. 2012; 93: 1051–1057.

2. Fekety R, McFarland LV, Surawicz CM, et al. Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin Infect Dis. 1997; 24: 324–333.

3. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010; 31: 431–455.

4. Pochapin M. The effect of probiotics on Clostridium difficile diarrhea. Am J Gastroenterol. 2000; 95: S11–S13.

5. Lawrence SJ, Korzenik JR, Mundy LM. Probiotics for recurrent Clostridium difficile disease. J Med Microbiol. 2005; 54: 905–906.

6. Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile–associated colitis in adults. Cochrane Database Syst Rev. 2008; : CD004611

7. Goldenberg JZ, Ma SS, Saxton JD, et al. Probiotics for the prevention of Clostridium difficile–associated diarrhea in adults and children. Cochrane Database Syst Rev. 2013; 5: CD006095

8. Deshpande A, Pasupuleti V, Mossad SB, et al. Use of Lactobacillus in prevention of recurrences of Clostridium difficile infection in solid organ transplant recipients. Accessed 19 March 2013. Infect Dis Clin Pract. 2013; .

Doi: 10.1097/IPC.0b013e31828d7231


9. Snydman DR. The safety of probiotics. Clin Infect Dis. 2008; 46:(suppl 2): S104–S111;

discussion S144–S151


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