Introduction Antibiotics disrupt the normal host colonic flora which is an important factor in thwarting the protective microbiota and one of the major risk factors for the development of both antibiotic associated diarrhea, which can occur in 30% of treated patients, and of Clostridium difficile associated diarrhea (C . difficile infection, CDI) [1], [2]. For the past 30 years, therapy of CDI has relied on the use of antimicrobial agents such as metronidazole and vancomycin. The Florastor® packaging claimed a weight rather Discussion Antibiotic associated diarrhea is common and the incidence and prevalence of C . difficile infection has increased over the past two decades [2], [3]. In clinical practice, more than 60% of patients either take an unsupervised probiotic or ask about the potential benefit about probiotic use when questioned before being prescribed an antibiotic (personal experience, EJCG). This raises the question of both efficacy in general and the role of proper dosing of specific probiotics for optimal results.

Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut. 2003;52:988–97. 10.1136/gut.52.7.988 Suche in Google Scholar PubMed PubMed Central [5] Lü M, Yu S, Deng J, Yan Q, Yang C, Xia G, et al. Peadiatr Drugs. 2009;11:243–9. doi: 10.2165/00148581-200911040-00003 . Suche in Google Scholar PubMed Supplementary Material The online version of this article offers supplementary material (DOI: https://doi.org/10.1515/dmpt-2019-0032 ).

Introduction/Objective: The Medical Director of a 150 bed Skilled Nursing Facility was faced with an outbreak of Clostridium difficile colitis. As part of the Infection Control QI process the Medical Director reviewed the literature and found the following evidence: Several studies and a Meta-Analysis synthesizing data from 25 randomized controlled trials (2) demonstrate effectiveness of three probiotics (Saccharomyces boulardii, Lactobacillus rhamnosus GG and probiotic mixtures) to reduce the development of antibiotic associated diarrhea.

Nonetheless, clinicians are currently utilizing probiotics in the transplant population, due to their benefit in gastrointestinal disorders, particularly recurrent Clostridium difficile. Limited knowledge and paucity of prospective trials in this patient population demands the need for completion of studies to identify the safety of probiotics in transplant patients.

Found typically in dietary supplements, probiotics can be safely used in the treatment of acute diarrheal disease, inflammatory bowel disease, and antibiotic-associated diarrhea. Research has shown that several strains of probiotics are helpful in the prevention and treatment of antibiotic-associated diarrhea.

Clinical Infectious Diseases 60(Suppl. 2): S66–71. Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M, Guyatt GH. (2012) Probiotics for the prevention of Clostridium difficile -associated diarrhea: a systematic review and meta-analysis. Annals of Internal Medicine 157(12): 878–888. Johnston BC, Lytvyn L, Lo CK, Allen SJ, Wang D, Szajewska H, Miller M, Ehrhardt S, Sampalis J, Duman DG, Pozzoni P, Colli A, Lönnermark E, Selinger CP, Wong S, Plummer S, Hickson M, Pancheva R, Hirsch S, Klarin B, Goldenberg JZ, Wang L, Mbuagbauw L, Foster G, Maw A, Sadeghirad B, Thabane L, Mertz D. (2018) Microbial preparations (probiotics) for the prevention of Clostridium difficile infection in adults and children: An individual patient data meta-analysis of 6,851 participants.

Reprints: Shira Idit Doron, MD, 750 Washington St, NEMC No. 238, Boston, MA 02111 (e-mail: sdoron@tufts-nemc.org ). Received for publication October 25, 2007; accepted November 7, 2007 Buy Abstract Antibiotic-associated diarrhea (AAD) occurs in approximately 25% of patients receiving antibiotics . Hospitalized patients with AAD are at increased risk for nosocomial infections and have a higher mortality. The results showed an overall reduction in the risk of AAD when probiotics were coadministered with antibiotics . McFarland conducted the largest meta-analysis to date analyzing 25 randomized controlled trials of probiotics for the prevention of AAD including 2810 subjects.

Patterson, Division of Pharmacy Practice and Administration, University of Missouri–Kansas City School of Pharmacy, 4245 Health Sciences Bldg, 2464 Charlotte St, Kansas City, MO 64108-2718 (pattersonmar@umkc.edu ). Search for other works by this author on: Bridget Bransteitter , Department of Medicine, Centerpoint Medical Center, Independence , Missouri, USA Search for other works by this author on: Lisa R Gillen Department of Pharmacy, Centerpoint Medical Center, Independence , Missouri, USA Search for other works by this author on: Received: 18 February 2020 Editorial decision: 08 May 2020 Corrected and typeset: 16 October 2020 PDF Split View Article contents Figures & tables Video Audio Supplementary Data Cite Cite Eric Wombwell, Mark E Patterson, Bridget Bransteitter, Lisa R Gillen, The Effect of Saccharomyces boulardii Primary Prevention on Risk of Hospital-onset Clostridioides difficile Infection in Hospitalized Patients Administered Antibiotics Frequently Associated With C. difficile Infection, Clinical Infectious Diseases , Volume 73, Issue 9, 1 November 2021, Pages e2512–e2518, https://doi.org/10.1093/cid/ciaa808 Close Email Twitter Facebook More Close Navbar Search Filter Microsite Search Term Search Abstract Background Hospital-onset Clostridioides difficile infection (HO-CDI) is a costly problem leading to readmissions, morbidity, and mortality. Conclusions Saccharomyces boulardii administered to hospitalized patients prescribed antibiotics frequently linked with HO-CDI was associated with a reduced risk of HO-CDI. (See the Editorial Commentary by McFarland on pages e2519–20.) Clostridioides difficile infection (CDI) has become one of the most common healthcare-associated infections in the United States, with the incidence nearly doubling between 2001 and 2010 [ 1 , 2 ]. The Centers for Disease Control and Prevention (CDC) considers CDI an urgent threat requiring prevention and monitoring [ 1 ]. Risk factors for CDI include increasing age, proton pump inhibitor (PPI) use, and most significantly, broad-spectrum antibiotics that are hypothesized to accelerate C. difficile colonization by reducing levels of beneficial bacteria that serve as barriers to infection [ 3 ]. Coadministering probiotics with antibiotics may prevent CDI development by reinforcing the barrier of good bacteria lost through antibiotic administration [ 4 , 5 ]. Beyond restoring altered intestinal microflora, administering probiotics may stimulate the immune system to prevent pathogen adhesion and invasion, and clear pathogens and toxins from the intestinal tract [ 6 ]. Saccharomyces boulardii , a specific yeast-derived probiotic, may prevent CDI by inducing direct inhibitory actions against C. difficile toxins [ 5 , 6 ]. Two studies demonstrate upregulation of total and specific intestinal antibodies (immunoglobulin A) to toxin A in response to S. boulardii exposure, consequently reducing C. difficile pathogenicity [ 7 , 8 ]. Other evidence demonstrates that S. boulardii directly inhibits C. difficile toxin by releasing a protease to hydrolyze C. difficile toxins [ 6 , 9 ]. The available literature examining the clinical outcomes of probiotics in preventing hospital-onset C. difficile infection (HO-CDI) is contentious.

Differential diagnosis It has been well documented that antibiotics place selective pressure on microflora and, as a result, people exposed to antibiotics may develop diarrhoea within 8 weeks of therapy.1 2 Antibiotic-associated diarrhoea (AAD) has been described as a patient-specific inflammatory infection which ranges in severity from diarrhoea (defined as an increase in frequency of ≥3 bowel movements per day with a decrease in consistency) with no additional complications to debilitating forms, such as colitis.3 4 Data estimate that AAD affects 3–29% of hospitalised patients receiving antibiotics, but only 33% are diagnosed as C difficile infections.5 Evidence that certain MRSA strains can cause diarrhoea and are enterotoxin-producing demonstrates a need to recognise MRSA as a possible causative agent of AAD.5 6 Stool specimens testing positive for MRSA establishes MRSA colonisation; however, it does not necessarily indicate MRSA AAD.5 According to Boyce et al 5 the following is necessary to classify MRSA AAD: negative stool assay for C difficile , no other identified enteric pathogen, diarrhoea unrelated to medications, heavy growth of MRSA in stool, and little or no normal flora. However, routine stool sampling is not recommended and should only be screened when diarrhoea is present.11 Intestinal decolonisation, also called intestinal decontamination or Selective Digestive Tract Decontamination (SDD), involves using oral non-absorbed medications to remove a specific pathogen or groups of pathogens cultivating in the intestines to circumvent the possibility of future infections in high-risk patients.1 Regimens historically contain agents impeding Gram-negative and fungal organisms that significantly reduced endogenous infections compared to oropharyngeal decontamination and standard care.14 27 However, SDD remains controversial.28 29 A 2003 Cochrane review of six studies found no benefit in using oral antimicrobials for routine decolonisation and suggested that there may be adverse reactions from systemic agents including rifampin and trimethoprim-sulfamethoxazole (TMP-SMX).20 Consequently, the IDSA recommends oral agents only for active infections of MRSA and suggests combining rifampin with doxycycline or TMP-SMX.19 Recently, proponents of SDD have recommended the addition of enteral vancomycin to the SDD regimen in order to eliminate the primary source of colonisation leading to endogenous MRSA infections in at-risk patients and reduce transmission to other patients.12 14 Enteral vancomycin is rarely absorbed in the blood, thereby providing a higher concentration in the stool and a means to eliminate MRSA from the intestinal flora.30 Multiple studies have demonstrated that the use of enteral vancomycin in eradicating MRSA from the intestines is safe and effective in various patient populations.5 12 24 26 29 30 On the contrary, the Hospital Infection Control Practices Advisory Committee, in collaboration with the Centre for Disease Control and Prevention, specifically recommend against the use of oral vancomycin in SDD to limit the emergence of vancomycin-resistant enterococci (VRE) and vancomycin-intermediate S aureus (VISA).29 Additional opponents of enteral vancomycin in accordance with SDD suggest that decolonisation may exacerbate antibiotic resistance.18–20 31–33 Intravenous agents, including vancomycin, produce fluctuating faecal concentrations following bilary excretion.28 29 Therefore, resistance may be formed in the intestine by the presence of low antibiotic concentration, which eliminates sensitive flora leading to overgrowth of antibiotic-resistant organisms.28 29 A meta-analysis concluded that prior exposure to the intravenous use of vancomycin (but not oral) is modestly associated with VRE colonisation.13 15 24 Additionally, studies involving two colonised MRSA patients with concurrent C difficile infections reported incomplete eradication of MRSA and an increase in VRE concentrations after therapy with enteral vancomycin 125 mg every 6 h.18 34 Even though these studies used a vancomycin dosing regimen that was therapeutic for C difficile infections it did not produce the intended effect.35 Alternatively, studies that orally administered 2 g/day of vancomycin provided complete eradication of MRSA and failed to substantiate any resistance.12 28 The absence of resistance may be explained by the high faecal concentration produced from utilising 2 g/day of enteral vancomycin, which far exceeds the minimum-bactericidal concentration of VISA and VRE.26 Some disregarded the lack of resistance reported in such studies as short-term effects that did not account for the development of resistance over time.