It’s time to rethink your approach to &lt;i&gt;C diff&lt;/i&gt; infection

,; ,; ,

doi:10.12788/jfp.0021

Applied Evidence

It’s time to rethink your approach to C diff infection

J Fam Pract. 2020 July;69(6):293-300 | 10.12788/jfp.0021

PDF Download

References

1. Polage CR, Gyorke CE, Kennedy MA, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med. 2015;175:1792-1801.

2. Reveles KR, Lee GC, Boyd NK, et al. The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010. Am J Infect Control. 2014;42:1028-1032.

3. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55(suppl 2):S88-S92.

4. Tariq R, Singh S, Gupta A, et al. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177:784-791.

5. Kachrimanidou M, Malisiovas N. Clostridium difficile infection: a comprehensive review. Crit Rev Microbiol. 2011;37:178-187.

6. O’Connor JR, Johnson S, Gerding DN. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology. 2009;136:1913-1924.

7. Kelly CP. A 76-year-old man with recurrent Clostridium difficile-associated diarrhea: review of C difficile infection. JAMA. 2009;301:954-962.

8. Cornely OA, Miller MA, Louie TJ, et al. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55(suppl 2):S154-S161.

9. Napolitano LM, Edmiston CE Jr. Clostridium difficile disease: diagnosis, pathogenesis, and treatment update. Surgery 2017;162:325-348.

10. Deshpande A, Pasupuleti V, Thota P, et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015;36:452-460.

11. 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:e1-e48.

12. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478-498; quiz 499.

13. Seto CT, Jeraldo P, Orenstein R, et al. Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility. Microbiome. 2014;2:42.

14. Chitnis AS, Holzbauer SM, Belflower RM, et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med. 2013;173:1359-1367.

15. Negrón ME, Rezaie A, Barkema HW, et al. Ulcerative colitis patients with Clostridium difficile are at increased risk of death, colectomy, and postoperative complications: a population-based inception cohort study. Am J Gastroenterol. 2016;111:691-704.

16. Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015;313:398-408.

17. Zar FA, Bakkanagari SR, Moorthi KM, et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45:302-307.

18. Johnson S, Louie TJ, Gerding DN, et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014;59:345-354.

19. Vancomycin: product details. Redbook Online. www.micromedexsolutions.com. Published 2018. Accessed June 13, 2020.

20. Mergenhagen KA, Wojciechowski AL, Paladino JA. A review of the economics of treating Clostridium difficile infection. Pharmacoeconomics. 2014;32:639-650.

21. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422-431.

22. Cornely OA, Crook DW, Esposito R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;12:281-289.

23. Crook DW, Walker AS, Kean Y, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials. Clin Infect Dis. 2012;55 suppl 2:S93-103.

24. Ford DC, Schroeder MC, Ince D, et al. Cost-effectiveness analysis of initial treatment strategies for mild-to-moderate Clostridium difficile infection in hospitalized patients. Am J Health Syst Pharm. 2018;75:1110-1121.

25. 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.

26. Panchal P, Budree S, Scheeler A, et al. Scaling safe access to fecal microbiota transplantation: past, present, and future. Curr Gastroenterol Rep. 2018;20:14.

27. Arbel LT, Hsu E, McNally K. Cost-effectiveness of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection: a literature review. Cureus. 2017;9:e1599.

28. Cammarota G, Ianiro G, Tilg H, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66:569-580.

29. Hocquart M, Lagier JC, Cassir N, et al. Early fecal microbiota transplantation improves survival in severe Clostridium difficile infections. Clin Infect Dis. 2018;66:645-650.

30. Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12:CD006095.

31. Johnston BC, Lytvyn L, Lo CK, et al. Microbial preparations (probiotics) for the prevention of Clostridium difficile infection in adults and children: an individual patient data meta-analysis of 6,851 participants. Infect Control Hosp Epidemiol. 2018:1-11.

32. Stewart DB, Hollenbeak CS, Wilson MZ. Is colectomy for fulminant Clostridium difficile colitis life saving? A systematic review. Colorectal Dis. 2013;15:798-804.

33. Julien M, Wild JL, Blansfield J, et al. Severe complicated Clostridium difficile infection: can the UPMC proposed scoring system predict the need for surgery? J Trauma Acute Care Surg. 2016;81:221-228.

34. Merck & Co, Inc. Sharp M. ZinplavaTM (bezlotoxumab [package insert] US Food and Drug Administration Web site. www.accessdata.fda.gov/drugsatfda_docs/label/2016/761046s000lbl.pdf. Revised October 2016. Accessed May 29, 2020.

35. Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305-317.

36. Chahine EB, Cho JC, Worley MV. Bezlotoxumab for the Prevention of Clostridium difficile recurrence. Consult Pharm. 2018;33:89-97.

37. Koo HL, Koo DC, Musher DM, et al. Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis. Clin Infect Dis. 2009;48:598-605.

38. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol. 2009;7:526-536.

39. Longtin Y, Paquet-Bolduc B, Gilca R, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C difficile infections: a quasi-experimental controlled study. JAMA Intern Med. 2016;176:796-804.

40. Teasley DG, Gerding DN, Olson MM, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983;2:1043-1046.

41. Wenisch C, Parschalk B, Hasenhündl M, et al. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996;22:813-818.

42. Pepin J, Alary ME, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-1597.

43. Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis. 2005;40:1586-1590.

44. Stevens VW, Nelson RE, Schwab-Daugherty EM, et al. Comparative effectiveness of vancomycin and metronidazole for the prevention of recurrence and death in patients with Clostridium difficile infection. JAMA Intern Med. 2017;177:546-553.

45. CutisPharma. FirvanqTM (vancomycin hydrochloride) for oral solution [package insert]. US Food and Drug Administration Web site. www.accessdata.fda.gov/drugsatfda_docs/label/2018/208910s000lbl.pdf. Revised January 2018. Accessed May 29, 2020.

46. Pettit NN, DePestel DD, Fohl AL, et al. Risk factors for systemic vancomycin exposure following administration of oral vancomycin for the treatment of Clostridium difficile infection. Pharmacotherapy. 2015;35:119-126.

What about surgical intervention?

In severe cases of CDI, surgery may be necessary and can reduce mortality.³² The surgical procedure with the strongest recommendation in the IDSA guidelines is the subtotal colectomy, though the diverting loop ileostomy is an alternative option.¹¹ Patients who may benefit from surgery include those with a WBC count ≥ 25,000; lactate > 5 mmol/L¹¹; altered mental status; megacolon; perforation of the colon; acute abdomen on physical examination; or septic shock due to CDI.³³ Although surgery can be beneficial, the mortality rate remains high for those with CDI who undergo colectomy.³³

Reserve bezlotoxumab for prevention of recurrence

Bezlotoxumab, a human monoclonal immunoglobulin GI/kappa antibody, was approved by the FDA in 2016 for the prevention of recurrent CDI. Its mechanism of action is to bind and neutralize C difficile toxin B. It was approved as a single infusion for adults who are receiving active antibiotic therapy for CDI and are considered to be at high risk for recurrence.³⁴

Fecal microbiota transplantation has been shown to be highly effective in 5 randomized clinical trials, with C difficile infection cure rates between 85% and 94%.

This approval was based on 2 trials of more than 2500 patients, in which participants received bezlotoxumab or placebo while receiving treatment for primary or recurrent CDI. The primary outcome of these studies was recurrent infection within 12 weeks after infusion, which was significantly lower for bezlotoxumab in both studies: 17% vs 28% (P < 0.001) in one trial and 16% vs 26% (P < 0.001) in the other trial.³⁵

Bezlotoxumab should only be used as an adjunct to prevent recurrence.³² There is no recommendation for or against bezlotoxumab in the IDSA guidelines because of the recent date of the drug’s approval. Its frequency of use will likely depend on the number of patients who meet criteria as high risk for recurrence and its estimated cost of $4560 per dose.^34,36

CASES

CASE 1: In light of Ms. O’s recent completion of a course of clindamycin and unremarkable lab work, she should be treated for mild-to-moderate CDI. She has no comorbid conditions to warrant fidaxomicin, and thus vancomycin (capsules or oral solution) would be the best treatment option. Ms. O is started on vancomycin PO 125 mg qid for 10 days. She is also advised to discontinue loperamide as soon as possible, based on poor outcomes data seen with the use of antimotility agents in CDI.³⁷

Continue to: CASE 2