Management ofClostridioides difficileinfection in adults and challenges in clinical practice: review and comparison of current IDSA/SHEA, ESCMID and ASID guidelines

Abstract

Clostridioides difficile infection (CDI) remains a significant clinical challenge both in the management of severe and severe-complicated disease and the prevention of recurrence. Guidelines released by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America (IDSA/SHEA) and ESCMID had some consensus as well as some discrepancies in disease severity classification and treatment recommendations. We review and compare the key clinical strategies from updated IDSA/SHEA, ESCMID and current Australasian guidelines for CDI management in adults and discuss relevant issues for clinicians, particularly in the management of severe-complicated infection. Updated IDSA/SHEA and ESCMID guidelines now reflect the increased efficacy of fidaxomicin in preventing recurrence and have both promoted fidaxomicin to first-line therapy with an initial CDI episode in both non-severe and severe disease and endorsed the role of bezlotoxumab in the prevention of recurrent infection. Vancomycin remains acceptable therapy and metronidazole is not preferred. For severe-complicated infection the IDSA/SHEA recommends high-dose oral ± rectal vancomycin and IV metronidazole, whilst in an important development, ESCMID has endorsed fidaxomicin and tigecycline as part of combination anti-CDI therapy, for the first time. The role of faecal microbiota transplantation (FMT) in second CDI recurrence is now clearer, but timing and mode of FMT in severe-complicated refractory disease still requires further study.

Review article: The epidemiology and management of Clostridioides difficile infection—A clinical update

“…four times daily for 10 days, or fidaxomicin 200 mg twice daily for 10 days for both an initial non-severe or severe CDI; however, the IDSA/SHEA and ESCMID now favour fidaxomicin over vancomycin as first line when available. 1,28,39,40 Another significant change in these updated guidelines was that metronidazole has fallen out of favour as a first line therapeutic option. Oral metronidazole 500 mg three times daily for 10 days should only be considered in low-risk patients with an initial non-severe episode, particularly in resource limited settings if alternate therapies are unavailable.…”

“…Oral metronidazole 500 mg three times daily for 10 days should only be considered in low-risk patients with an initial non-severe episode, particularly in resource limited settings if alternate therapies are unavailable. 1,28,[39][40][41] However, the Australasian Society of Infectious Diseases (ASID) guidelines which were last updated in 2016 recommend metronidazole, without vancomycin, for initial non-severe infections (Figure 1). 42 Fidaxomicin is preferred over vancomycin by the IDSA and ESCMID unless unavailable, with moderate quality evidence.…”

“…1,2 Intravenous metronidazole 500 mg three times daily is also recommended in conjunction with vancomycin by most medical societies with the exception of the ESCMID, as overall data on the combination therapy is limited. 28,40 A large two-center retrospective cohort study of patients with non-fulminant and fulminant CDI between 2010 and 2018 compared the efficacy of vancomycin monotherapy and combined vancomycin with intravenous metronidazole. 70 Combination vancomycin and metronidazole therapy for non-fulminant or fulminant infections was not superior to vancomycin monotherapy, and was not associated with reduced rates of 90-day colectomy or death (adjusted OR 1.07; 95% CI 0.79-1.45), or reduced recurrence (adjusted OR 1.16; 95% CI 0.86-1.57).…”

“…74 Tigecycline is a glyclycycline antibiotic which has been shown to treat C. difficile in vitro with suppression of toxin production and sporulation, though has not yet been studied with intravenous administration in randomised clinical trials. 40,75 One single center retrospective cohort study of patients with severe CDI compared treatment with intravenous tigecycline (loading dose of 100 mg followed by 50 mg twice daily) to oral vancomycin with intravenous metronidazole and found improved cure rates (76% compared to 53%, respectively) with reduced rates of CDI-related complications and sepsis. 76 While there have been further observational cohort studies that have demonstrated efficacy of tigecycline as an adjunct therapy in severe or fulminant disease, several other studies found no benefit compared to standard of care antimicrobials with regard to cure or recurrence rates.…”

“…In cases of greater than one recurrent infection, treatment options include fidaxomicin, tapered and pulsed vancomycin, or standard vancomycin with subsequent rifaximin 400 mg three times daily for 20 days (the latter with low quality evidence). 39,40 However, it is important to consider resistance patterns when considering rifaximin.…”