Do Probiotics Have a Role in the Prevention of Clostridium Difficile Diarrhea?

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23/09/19 Sciences Reference this

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Topic: Do probiotics have a role in the prevention of Clostridium difficile diarrhea?


Clostridium difficile is a bacterial infection that results in almost half a million cases annually.1 It typically occurs following or during the use of antibiotics, due to the disruption of bacteria in gut flora. Symptoms typically include colitis and frequent loose watery stools. C. difficile is seen in all ages, but is common among older patients, especially those in long-term care facilities or those hospitalized for a long period of time. C. difficile is a spore-producing bacteria and because of this, it is highly contagious. It is also because of this, that treatment for C. difficile is rigorous and includes strict isolation of the patient, discontinuation of the suspected antibiotic and initiation of oral vancomycin, good hygiene, and nutrition.2 Patients that get C. difficile are more likely to get recurrent infection, and prophylactic treatment is limited. Current recommendations for preventing C. difficile include frequent hand-washing if caring for a patient with C. difficile, as well as daily sporicidal disinfection.2 In recent years, studies have suggested the use of probiotics for primary prevention in patients susceptible to infection. This is because probiotics replenish the gut with the bacteria lost from antibiotics, and thus preventing C. difficile associated diarrhea. However, these suggestions have not been accepted by the Infectious Diseases Society of America because there has not been enough evidence to conclude the use of probiotics for primary prevention.2 It is important to evaluate the use of probiotics for the prevention of C. difficile associated diarrhea since the patient population is typically at greater risk of more serious complications due to dehydration, such as older patients and immunocompromised patients.

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A meta-analysis composed of randomized controlled trials assessed the use of probiotics for the prevention of Clostridium difficile-associated diarrhea (CDAD). Thirty-one trials (8672 participants) showed that probiotics reduced the risk of CDAD by 60%. Trials that enrolled participants at high risk for the development of CDAD (> 5%) claimed that probiotics reduced the risk of CDAD by 70%. Adult and pediatric patients who received antibiotic therapy were included in the meta-analysis. Moreover, inpatient and outpatient participants originated from several countries. The incidence of CDAD was the primary outcome. The detection of C. difficile in stool, adverse events, antibiotic-associated diarrhea, and length of hospital stay were secondary outcomes. The most prevalent adverse events were abdominal cramping, nausea, fever, flatulence, and soft stools.

The Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older patients (PLACIDE) trial was a randomized, double-blind trial.  Patients were included in this study if they were at least 65 years of age and were on either oral or intravenous antibiotic therapy at least 7 days prior.  Patients were randomized into groups by a computer software to receive either a combination probiotic of lactobacilli and bifidobacteria for twenty- one days, or a placebo, with 1493 patients receiving the probiotic and 1488 receiving placebo.4  Each patient was monitored closely daily by researchers and stool samples were collected for testing after each occurrence.  However, not all stool samples were able to be collected and tested for C.difficile due to some patients having a milder and shorter case of antibiotic-associated diarrhea.  In this study, the primary outcome was antibiotic-associated diarrhea within eight weeks of starting the trial as well as C. difficile within 12 weeks.4  After the conclusion of the trial and interpretation of results, it was found that the probiotic combination capsule did not provide any more protection against C. difficile than placebo. 

 Secondary endpoints included length of hospital stay and the severity of the diarrhea.  Antibiotic-associated diarrhea occurred in 10.8% of patients taking the probiotic combination and in 10.4% of patients taking placebo.  Of those patients, C. difficile occurred in 0.8% of patients on the probiotic supplement and 1.2% of those taking placebo.4  This evidence is not sufficient enough to claim that probiotics are helpful in preventing antibiotic-associated diarrhea, specifically C. difficile.  Also, results from the trial indicate that the production of lactic acid from this probiotic formula did not show any effect on patients developing antibiotic-associated diarrhea. 

 At the time, this trial was the largest trial completed that studied the correlation between probiotics and C. difficile.  More testing should be done against other probiotic strains to see if they provide any protection against C. difficile infections.  A weakness of this trial is that not many cases of antibiotic-associated diarrhea was actually caused by C. difficile.   This information makes it difficult to draw a formal conclusion that probiotics play a role in C. difficile prevention.  Although patients remained adherent to the probiotic/placebo during the trial, an increasing pill burden for the older population could pose an issue.  Most elderly patients are already on several medications and this could cause patients to potentially be non-compliant outside the means of a trial. 

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After evaluating statistics from both sides of this controversial debate we suggest adding a probiotic formula, especially in patients who are at a higher risk of developing C. difficile infections.  Probiotics will help to replenish the good bacteria in the gut that is destroyed by antibiotics and therefore promote a healthy gastrointestinal tract, and there is no harm to the patient by adding a probiotic to their at- home medication regimen.  Both sides of this argument presented promising data, but statistics urging the addition of a probiotic proved to be the most promising in that they decreased the risk of C. difficile infections by 70%.3  According to a journal article evaluating the cost-effectiveness of using probiotics for prevention of C. difficile diarrhea, all hospitalized patients receiving 1 capsule of probiotics daily in conjunction with antibiotic therapy lowered the overall risk of C. difficile diarrhea and resulted in a savings of $518 per patient.5  After evaluating cost of treatment of both C. difficile prevention and treatment, adding a probiotic in patients who are at risk, such as older patients and those who are immunocompromised, will have a decreased financial burden in the long-run, and is why we suggest adding this supplement. This would also decrease the financial burden for hospitals by reducing length of stays for patients as well as reducing the costs to treat and prevent C. difficile. Adding a probiotic regimen in conjunction with antibiotic therapy should be done in all patients receiving antimicrobial therapy to reduce the incidence of C. difficile diarrhea, because it will reduce the financial burden in patients and hospitals, and will reduce the risk of more serious complications in patients at higher risk, including older patients and immunocompetent patients.



  1. Clostridioides difficile infection | HAI | CDC. Updated 2019. Accessed Jan 16, 2019.
  2. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for clostridium difficile infection in adults and children: 2017 update by the infectious diseases society of america (IDSA) and society for healthcare epidemiology of america (SHEA). Clin Infect Dis. 2018;66(7):e48. doi: 10.1093/cid/cix1085.
  3. Goldenberg  JZ, Yap  C, Lytvyn  L, Lo  CKF, Beardsley  J, Mertz  D, Johnston  BC. Probiotics for the prevention of Clostridium difficileā€associated diarrhea in adults and children. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD006095. DOI: 10.1002/14651858.CD006095.pub4.
  4. Allen, Stephen J, Prof, Wareham, Kathie, MPH, Wang, Duolao, PhD, et. al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and clostridium difficile diarrhoea in older inpatients (PLACIDE): A randomised, double-blind, placebo-controlled, multicentre trial. Lancet, The. 2013;382(9900):1249-1257.
  5. Leal JR, Heitman SJ, Conly JM, Henderson EA, Manns BJ. Cost-effectiveness analysis of the use of probiotics for the prevention of clostridium difficile-associated diarrhea in a provincial healthcare system. Infect Control Hosp Epidemiol. 2016;37(9):1079-1086. Accessed Jan 18, 2019. doi: 10.1017/ice.2016.134.

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