A C difficile two-fer

Two recent review articles on Clostridium difficile are quite useful:

  • Mezoff EA, Cohen MB. J Pediatr 2013; 163: 627-30.
  • Dupont HL. Clin Gastroenterol Hepatol 2013; 11: 1216-23.

The first publication reviews acid suppression and the risk of C difficile infection (CDI).  It starts off with  a terrific piece of advice from Sir William Osler: “One of the first duties of the physician is to educate the masses not to take medicine.”  The authors note that pH above 4 has been shown to increase bacterial survival, including  C perfringe spores in a mouse model.  In addition, the article notes that there have been concerns as early as 1982 that acid suppression could be a risk factor for CDI.  Several recent studies were summarized, including the following:

  • A recent meta-analysis (Kwok CS et al. Am J Gastroenterol 2012; 107: 1011-9) with 42 studies (N= 313,000 patients) “found an association between PPI use and risk of CDI (OR1.74, 05%CI 1.47-2.85).”
  • A review of the literature (Deshpande A et. Clin Gastroenterol Hepatol 2012; 10: 225-33) between 1990-2010 found an overall increase in CDI risk with PPIs to be OR 2.15 (95% CI 1.81-2.55). No prospective studies were identified.
  • In pediatrics, a study (Turco et al. Alimentary Pharmacol Therapeut 2010; 31: 754-9) with 910 children admitted for abdominal pain and diarrhea identified 68 with CDI.  Compared with control patients, use of PPIs was significantly higher in CDI patients (OR 4.52, 95% CI 1.4-14.4).

The FDA has stated that PPIs may be associated with an increased risk of CDI.  In addition, the use of antibiotics “appear to act synergistically with PPIs.”  Thus, the authors recommend stopping PPIs in those who do not need them.  Periodic ‘holidays’ or dosing step-downs may help assess continued need for PPIs.

The second publication succinctly reviews the diagnosis and management of CDI.  The various diagnostic methods are compared in Table 1.  Therapeutic options for 1st time infection are reviewed in Table 2.  For adults with mild-to-moderate infections, metronidazole (500 mg TID for 10 days) is preferred.  Vancomycin or Fidaxomicin are recommended for more severe infections.

Table 3 lists treatment options for recurrent CDI.  Repeat course of any of the 1st round treatments can be considered depending on patient’s illness severity.  In addition, other potential treatments included the following:

  • vancomycin tapered dose (week 1: 125 mg 4 times/day, week 2: 125 mg 2 times/day, week 3: 125 mg once/day, week 4: 125 mg every other day, week 5 & 6: 125 mg every third day)
  • rifaximin (550 mg BID x 20 days)
  • high-dose vancomycin (250-500 mg 4 times/day for 10 days) followed by S boulardii (2 capsules BID for 28 d)
  • fecal microbiota transfer (FMT) –“although family member stool donors have been used, the current movement is toward volunteer donor pools.”  [I do not think ‘current movement’ was intended as a pun by the authors.]  Volunteer donors could lower the screening costs.
  • intravenous immunoglobulin (small clinical trials have failed to show efficacy)
  • monoclonal antibodies to toxins A/B

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Probiotics for Crohn’s Disease –No Beneficial Effects Noted

With all the buzz regarding how a patient’s microbiome seems to affect everything from metabolic syndrome and colic to autoimmune diseases and inflammatory bowel disease, more attention has been paid in attempts to alter the microbiome for therapeutic benefits.  In Crohn’s disease (CD), the fact that antibiotics have shown beneficial effects have led to a number of studies of probiotics.  A recent study, like previous ones, did not demostrate any benefit with Saccharomyces boulardii (Clin Gastroenterol Hepatol 2013; 11: 982-87).

In this prospective double-blind, placebo-controlled study of 165 patients who achieved remission after steroids or salicylates, subjects were randomly assigned to groups given S boulardii (1 gram per day) or placebo for 52 weeks.

Results:

  • CD relapse occurred in 80 patients: 38 (47.5%) in the probiotic group  and 42 (53.2%) in the placebo group
  • Time to relapse did not differ significantly: 40.7 weeks in probiotic group vs 39 weeks in placebo group
  • No differences were seen in disease activity scores or serum inflammatory markers
  • In post hoc analysis, nonsmokers given S boulardii were less likely to experience a relapse compared with nonsmoker control patients (34.5 % vs. 72%)

One important limitation of this study was not examining the effects of the probiotic on the microbiome of these patients.  Perhaps, other probiotics would be more effective in restoring a “healthy” flora.

Based on these results, and others, the accompanying editorial (pg 988-89), advocates use of probiotics only for prevention of antibiotic-associated diarrhea, prevention of recurrent Clostridium difficile, and treatment/prevention of pouchitis.

Bottom-line: Probiotics have not been demonstrated to be helpful for Crohn’s disease.

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