Clinicians look at optimal approaches for trying to avoid Clostridioides difficile infection (CDI).
CDI is one of the most costly and common healthcare-associated infections in the United States with an incidence of approximately half a million cases resulting in an estimated cost of 6 billion dollars annually.1,2 Broad spectrum antibiotics are one of the biggest risk factors for developing CDI, with third generation cephalosporins (OR 3.2) and clindamycin (OR 2.9) having the highest risk.3 Approximately 20-25% with an initial CDI episode experience recurrent CDI (rCDI) with risk of recurrence mounting with each subsequent episode.4 Systemic antibiotic exposure following the initial CDI episode is a primary risk factor for recurrence.5 The optimal approach for preventing CDI and rCDI remains unknown.6
CDI prophylaxis is lacking in high-quality evidence and the risk/benefit must be weighed due to disruption to the gut microbiome.7 There have been several studies published on the use of secondary CDI prophylaxis. Most studies were retrospective and endured significant heterogeneity, but majority demonstrated significantly lower rates of rCDI with administration of oral vancomycin therapy (OVP) in high-risk patients taking systemic antibiotics.8,9 In a meta-analysis of 11 studies, 10 retrospective, OVP for primary and secondary prophylaxis was associated with a lower rate of CDI compared with no intervention (OR 0.13) and a subgroup analysis showed the lowest OVP dosage (125 mg once daily) was the best.10 No difference was seen between groups regarding the onset of vancomycin-resistant Enterococcus infections.9,10 The American College of Gastroenterology (ACG) conditionally recommend OVP for secondary CDI prophylaxis in high-risk patients requiring subsequent treatment with systemic antibiotics. ACG guidelines define high-risk patients as those aged 65 years or older or with significant immunocompromised conditions or therapies who were hospitalized for severe CDI within the past 3 months. Both the ACG and IDSA/SHEA recommend vancomycin 125 mg once daily continued until 5 days after completion of systemic antibiotics, but optimal dosing and duration strategies have not been defined in prospective studies.6,8,11 Lower doses and caution should be used when recommending OVP for CDI prevention since oral vancomycin is not C difficile specific and can cause significant dysbiosis and recurrence.7,8
Another potential strategy for CDI prevention may be through dysbiosis prevention. Rebyota is the only FDA approved microbiome-based therapy administered as a single dose after completion of standard CDI antibiotic therapy to prevent rCDI.12,13 SER-109 is another potential microbiome therapy administered as a single oral dose after completion of CDI therapy to prevent rCDI. In a phase 3 clinical trial, ECOSPOR III, SER-109 demonstrated superiority over placebo in reducing rCDI (12% vs. 40%, p < 0.001) and had a favorable safety profile.14 Ribaxamase (SYN-004) is a poorly absorbed, orally administered β-lactamase designed to protect the microbiota from the disruption caused by systemic β-lactam agents. In a phase 2b RCT use of ribaxamase reduced the incidence of CDI in patients receiving ceftriaxone without decreasing antibiotic efficacy.15
No effective or proven strategies are available for the primary prevention of CDI. Several promising strategies are in clinical development including microbiota-based therapies and vaccine development.16 At this time, OVP represents a reasonable strategy for secondary prophylaxis in high risk patients requiring systemic antibiotics. Further studies are ongoing on the optimal OVP schedule including dose and duration.10 Other strategies include fecal microbiota transplantation, which has proved to be a very effective treatment for patients with multiple recurrences.6 Bezlotoxumab, a monoclonal antibody that binds to toxin B, provides protection against rCDI, mainly in patients with primary episodes and high risk of relapse.17 Further strategies for preventing primary and secondary CDI are warranted.
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16.Businesswire. Phase 3 CLOVER Trial for Pfizer’s investigational Clostridioides difficile vaccine indicates strong potential effect in reducing duration and severity of disease based on secondary endpoints. March 01, 2022. Phase 3 CLOVER Trial for Pfizer’s Investigational Clostridioides Difficile Vaccine Indicates Strong Potential Effect in Reducing Duration and Severity of Disease Based on Secondary Endpoints | Business Wire.
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