From the Guidelines
The treatment for a first recurrence of Clostridioides difficile (C. diff) infection should be fidaxomicin 200 mg given twice daily for 10 days, as it is associated with lower recurrence rates due to its spore-sparing properties and minimal disruption of gut microbiota, as recommended by the 2021 focused update guidelines on management of Clostridioides difficile infection in adults 1.
Key Considerations
- For patients who were initially treated with metronidazole, switching to vancomycin is recommended as metronidazole should not be used for recurrent infections due to increased risk of neurotoxicity with prolonged use and higher failure rates.
- In cases where the first episode was treated with vancomycin, using a tapered and pulsed vancomycin regimen may be beneficial (e.g., 125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks) 1.
- Bezlotoxumab, a monoclonal antibody against C. diff toxin B, may be considered as an adjunctive therapy for patients at high risk for additional recurrences, administered as a single intravenous infusion during antibiotic treatment 1.
Treatment Options
- Fidaxomicin 200 mg twice daily for 10 days
- Vancomycin 125 mg given 4 times daily by mouth for 10 days
- Vancomycin by mouth in a tapered and pulsed regimen
- Bezlotoxumab 10 mg/kg given intravenously once during administration of standard of care antibiotics
Rationale
The 2021 focused update guidelines on management of Clostridioides difficile infection in adults recommend fidaxomicin as the preferred treatment for a first recurrence of C. diff infection, due to its lower recurrence rates and minimal disruption of gut microbiota 1. The guidelines also suggest that vancomycin in a tapered and pulsed regimen or vancomycin as a standard course are acceptable alternatives for a first CDI recurrence 1. Bezlotoxumab may be considered as an adjunctive therapy for patients at high risk for additional recurrences 1.
From the FDA Drug Label
In subjects with diarrhea resolution at end-of-treatment with Vancomycin Hydrochloride Capsules, recurrence of CDAD during the following four weeks occurred in 25 of 107 (23%) and 18 of 102 (18%) in Trial 1 and Trial 2, respectively.
The treatment for the first recurrence of Clostridioides difficile (C. diff) infection is not directly stated in the provided drug label. 2
From the Research
Treatment Options for First Recurrence of C. diff Infection
- A first recurrence of C. diff infection may be treated with the same regimen as the first episode, with metronidazole 500 mg q 8 h for 10-14 days being the drug of choice for moderate infection, and vancomycin 125 mg q 6 h for 10-14 days being the drug of choice for severe CDI 3.
- Fidaxomicin has been shown to be similar to vancomycin in achieving a clinical response at the end of therapy, but superior in preventing a second recurrence within 28 days in patients with a first recurrence of CDI 4.
- Alternative agents for treatment of recurrent CDI include fecal bacteriotherapy, a "rifaximin chaser," nitazoxanide, probiotics, and intravenous immunoglobulin 3.
Comparison of Treatment Options
- Fecal microbiota transplantation (FMT) has been found to be superior to fidaxomicin or vancomycin in treating recurrent CDI, with higher rates of clinical and microbiological resolution or clinical resolution alone 5.
- Fidaxomicin has been shown to be more effective than vancomycin in achieving clinical cure in the presence of concomitant antibiotic therapy and in preventing recurrence regardless of concomitant antibiotic use 6.
- Standardized microbiome-based therapies, such as SER-109 and RBX2660, have demonstrated high efficacy rates in reducing recurrence rates of CDI and are now US Food and Drug Administration approved for recurrent CDI 7.
Considerations for Treatment
- The use of concomitant antibiotics during CDI treatment has been associated with a lower cure rate and an extended time to resolution of diarrhea, highlighting the need for careful consideration of antibiotic use in patients with CDI 6.
- Fecal microbiota transplantation has traditionally been considered safe, but significant heterogeneity and a lack of standardization regarding the process of preparation and administration remain a major pitfall 7.