What are some major challenges associated with C. difficile infection?
C. difficile Microbiology
A major challenge of combating infection is that the C. difficile spores are durable in the anaerobic [oxygen poor] environment of the gut and can survive on inanimate surfaces outside the body for 3-6 months in a dormant state (40). These spores are resistant to heat, acid, and antibiotics. This makes C. difficile easy to transmit in hospitals and other healthcare settings and exceptionally hard to eliminate (40).
There also exists a strain of C. difficile that is hypervirulent [exceptionally capable of resulting in severe illness]: NAP1/BI/027. This strain produces more levels of toxins released by other strains C. difficile (41) and has even been reported to produce an additional type of toxin (42). It is resistant to fluoroquinolones (43), a type of antibiotic, and has been shown to be associated with lower cure rates and increased rates of recurrence (44-46). It has also been shown to cause severe disease, higher rates of intensive care unit admissions, colectomy procedures, and death (47).
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A main challenge associated with C. difficile infection, as previously mentioned, is recurrence of the infection. After the first C. difficile infection is treated, 10-25% of patients will experience at least one new infection (49, 50). This percentage jumps up to 65% if they’ve previously had two episodes of C. difficile infection (49, 50). A proposed mechanism that may contribute to recurrences is a weakened immune response to C. difficile toxins coupled with new exposure to spores (51).
Infection Recurrence
Although many diagnostic tests exist, no single test exists as a stand-alone test to confirm the presence of a C. difficile infection, according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) (48). The currently available tests lack sensitivity and specificity. The multiple states of infection that C. difficile can present also complicates testing (40). As described above, C. difficile can cause either asymptomatic colonization (in carriers) or active infection. The current tests do not have a clear differentiation between these two states (40). The proposed solution to optimizing diagnosis relies on combining two tests (48). Current guidelines recommend testing for C. difficile infection only when a patient has diarrhea and there is reasonable suspicion for an infective cause (5).
Diagnostic Testing
Antibiotic Treatment
The optimal antibiotic treatment for recurrent C. difficile infection has not yet been well-established. Antibiotic treatment options used in initial C. difficile treatments such as vancomycin and fidaxomicin do not reach satisfactory rates of effectiveness in recurrence episodes (5). Although alternative treatment options are available, such as FMT, antibiotics remain the primary treatment method.
References
5. McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, 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):e1-e48.
40. Moore SC. Clostridium difficile: More Challenging than Ever. Crit Care Nurs Clin North Am. 2018;30(1):41-53.
41. Geric B, Rupnik M, Gerding DN, Grabnar M, Johnson S. Distribution of Clostridium difficile variant toxinotypes and strains with binary toxin genes among clinical isolates in an American hospital. J Med Microbiol. 2004;53(Pt 9):887-94.
42. Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet. 2005;366(9491):1079-84.
43. Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis. 2005;41(9):1254-60.
44. Petrella LA, Sambol SP, Cheknis A, Nagaro K, Kean Y, Sears PS, et al. Decreased cure and increased recurrence rates for Clostridium difficile infection caused by the epidemic C. difficile BI strain. Clin Infect Dis. 2012;55(3):351-7.
45. Walker AS, Eyre DW, Wyllie DH, Dingle KE, Griffiths D, Shine B, et al. Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection. Clinical Infectious Diseases: Infectious Diseases Society of America. 2013;56(11):1589-600.
46. Marsh JW, Arora R, Schlackman JL, Shutt KA, Curry SR, Harrison LH. Association of relapse of Clostridium difficile disease with BI/NAP1/027. J Clin Microbiol. 2012;50(12):4078-82.
47. See I, Mu Y, Cohen J, Beldavs ZG, Winston LG, Dumyati G, et al. NAP1 strain type predicts outcomes from Clostridium difficile infection. Clin Infect Dis. 2014;58(10):1394-400.
48. Crobach MJ, Planche T, Eckert C, Barbut F, Terveer EM, Dekkers OM, et al. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2016;22 Suppl 4:S63-81.
49. Cole SA, Stahl TJ. Persistent and Recurrent Clostridium difficile Colitis. Clinics in Colon and Rectal Surgery. 2015;28(2):65-9.
50. Johnson S. Recurrent Clostridium difficile infection: A review of risk factors, treatments, and outcomes. Journal of Infection. 2009;58(6):403-10.
51. Simor AE. Diagnosis, management, and prevention of Clostridium difficile infection in long-term care facilities: a review. J Am Geriatr Soc. 2010;58(8):1556-64.
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