Clostridium difficile;

Is oral vancomycin prophylaxis (OVP) effective in preventing recurrent Clostridium difficile infection (CDI) in patients requiring systemic antimicrobial therapy (SAT)?

FA Manian MD, MPH, , , , , Leave a comment

Although OVP is often administered to patients with history of CDI who require SAT, evidence to support this practice has been lacking until recently.

In a 2016 retrospective study of 203 patients with prior history of CDI, those who received OVP (125 mg or 250 mg 2x/daily) during the course of their SAT and for up to 1 week thereafter were significantly less likely to have a recurrence than the non-OVP group (4.2% vs 26.6%, respectively, O.R. 0.12 [C.I. 0.04-0.4]) (1). In this study, the mean interval between prior CDI and initiation of prophylaxis was 6.1 months (1-21 months), and the mean duration of prophylaxis following discontinuation of SAT was 1 day (0-6 days). Similar results have been reported by others (2,3).

Despite their retrospective nature, these studies lend support to the use of OVP in reducing the risk of recurrent CDI in patients who require SAT. It is unclear how long OVP should be continued after SAT is completed, if at all, but common practice is 1-2 weeks.

A randomized-controlled study comparing OVP 125 mg daily for the duration of SAT plus 5 days vs placebo appears to be on the way (4)!

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References

  1. Van Hise NW, Bryant AM, Hennessey EK, Crannage AJ, Khoury JA, Manian FA. Efficacy of oral vancomycin in preventing recurrent Clostridium difficile infection in patients treated with systemic antimicrobial agents. Clin Infect Dis 2016; Advance Access published June 17, 2016. Doi.10.1093/cid/ciw401.
  2. Carignan A, Sebastien Poulin, Martin P, et al. Efficacy of secondary prophylaxis with vancomycin for preventing recurrent Clostridium difficile infections. Am J Gastroenterol 2016;111: 1834-40. https://www.ncbi.nlm.nih.gov/pubmed/27619835
  3. Granetsky A, Han JH, Hughes ME, et al. Oral vancomycin is highly effective in preventing Clostridium difficile infection in allogeneic hematopoietic stem cell transplant recipients. Blood 2016;128:2225; http://www.bloodjournal.org/content/128/22/2225?sso-checked=true
  4. https://clinicaltrials.gov/ct2/show/NCT03462459

Disclosure: The author of this post was also a co-investigator of one of the studies cited (ref. 1).

 

 

 

Is oral vancomycin prophylaxis (OVP) effective in preventing recurrent Clostridium difficile infection (CDI) in patients requiring systemic antimicrobial therapy (SAT)?

Is oral metronidazole (Flagyl®) effective in reducing the risk of recurrent Clostridium difficile infection (CDI)?

FA Manian MD, MPH, , Leave a comment

To date only 1 study has attempted to evaluate metronidazole’s role in preventing CDI1. This work, however,  has significant shortcomings including its retrospective nature, definition of metronidazole prophylaxis as any dose for reasons other than CDI starting 1-3 days before initiation of the primary antibiotic, undefined duration, less comorbidities in the metronidazole group, and surveillance period for CDI limited to only 7 days following initiation of the primary antibiotic. For these reasons, it is difficult to interpret the results of this study whose conclusion was that metronidazole may protective against CDI2.

In fact, there are several reasons why metronidazole prophylaxis may not be effective in CDI.   First, due to its very high bioavailability, concentrations of metronidazole in formed stool are often undetectable2,3 . Consequently, “preventive” metronidazole in patients at risk of CDI but with formed stools would not be expected to achieve high enough concentrations in the colon to be effective.  In additions, metronidazole itself may be associated with CDI4 and  vancomycin-resistant enterococci5,  and has several potential drug-interactions and adverse effects6 .

References

  1. Rodriguez S, Hernandez MB, Tarchini G, et al. Risk of Clostridium difficile infection in hospitalized patients receiving metronidazole for a non-C difficile infection. Clin Gastroenterol Hepatol 2014;12:1856-61. https://www.ncbi.nlm.nih.gov/pubmed/24681079
  2. Dupont HL. Chemoprophylaxis of Clostridium difficile infections in high-risk hospitalized patients. Clin Gastroenterol Hepatol 2014;12: 1862-63. https://www.ncbi.nlm.nih.gov/labs/articles/24768812/
  3. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut 1986;27:1169-1172. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1433873/pdf/gut00370-0065.pdf
  4. Daly JJ, Chowdary KV. Pseudomembranous colitis secondary to metronidazole. Dig Dis Sci 1983;28:573-4.
  5.  Carmeli Y, Eliopoulos GM, Samore MH. Antecedent treatment with different antibiotic agents as a risk factor for vancomycin-resistant enterococcus. Emerg Infect Dis 2002;8:802-807. https://wwwnc.cdc.gov/eid/article/8/8/pdfs/01-0418.pdf
  6. Salvatore M, Meyers BR. Metronidazole. In Mandel, Douglas, Bennett’s Principles and Practice of Infectious Diseases-7th Ed. p. 419-426. 2010, Churchill Livingstone, Philadelphia.

 

 

Is oral metronidazole (Flagyl®) effective in reducing the risk of recurrent Clostridium difficile infection (CDI)?