Management of Clostridioides difficile Infections After Hematopoietic Stem Cell Transplantation

Treatment Options

The initial treatment of C diff infection is 10 days of oral antibiotics, with vancomycin or fidaxomicin as the first choice. Vancomycin is dosed at 125 mg 4 times a day, and fidaxomicin is dosed at 200 mg twice daily.⁴ Fidaxomicin has been shown to have lower recurrence rates of C diff infection following treatment. However, due to cost, it may not be an option for initial treatment for some patients.⁶

There are some benefits to fidaxomicin that may make it a more appropriate treatment for those with C diff infection post-HSCT. This patient population is at a higher risk for recurrence, and fidaxomicin has shown lower rates of recurrent infection compared with vancomycin.

Fidaxomicin also preserves other natural bacteria in the intestines, decreasing the risk of vancomycin-resistant bacteria.⁶

For people who develop a recurrent C diff infection, pulse vancomycin with a taper may be necessary. If vancomycin was used for the first course of antibiotics, fidaxomicin can be given for the first recurrence.⁴ For second and subsequent recurrences, fidaxomicin can be used if vancomycin and vancomycin with taper were used for previous infections.

Another option is an infusion of bezlotoxumab in combination with vancomycin.⁴ Bezlotoxumab is a monoclonal antibody that works against C diff toxin B. Studies have shown bezlotoxumab to be effective in reducing the recurrence of C diff infection, and is well-tolerated without many infusion reactions or serious adverse effects.⁷

Fecal microbiota transplant also is a potential treatment for C diff. During this procedure, stool from a healthy donor is transplanted into the patient with C diff, either through NG tube, capsules, or during colonoscopy. Although studies have demonstrated the safety and effectiveness of fecal microbiota transplant in post-HSCT patients, there are still risks associated with giving live microbes to someone who may be immunocompromised.⁸

Probiotics are not recommended for patients who have undergone HSCT for the prevention of C diff infection. The use of probiotics in those who are immunocompromised increases their risk for developing sepsis and bacteremia.⁸

Quickly identifying the cause of diarrhea in a patient who has undergone HSCT is important to determine the best course of treatment and prevent serious complications. In the case of C diff infection, the first choice of antibiotics should be vancomycin or fidaxomicin. A different schedule of vancomycin may be considered to treat recurrence of infection, as well as administration of bezlotoxumab.

References

1. C. difficile infection: Symptoms and causes. Mayo Clinic. Accessed November 17, 2021. https://www.mayoclinic.org/diseases-conditions/c-difficile/symptoms-causes/syc-20351691
2. Abou Chakra CN, McGeer A, Labbé AC, et al. Factors associated with complications of Clostridium difficile infection in a multicenter prospective cohort. Clin Infect Dis. 2015;61(12):1781-1788. doi:10.1093/cid/civ749
3. Chung S, Abou Mourad Y. Clostridium difficile infection among hematopoietic stem cell transplant recipients and subsequent development of graft-versus-host disease. Blood. 2019;134(Supplement_1):4494. doi:10.1182/blood-2019-129663
4. Melnyk T. Clostridium difficile infection management in adults undergoing stem-cell transplant. J Hematol Oncol Pharm. Published online February 19, 2020.
5. Centers for Disease Control and Prevention (CDC). C. diff (Clostridioides difficile): FAQs for clinicians about C. diff. CDC website. Accessed November 17, 2021. https://www.cdc.gov/cdiff/clinicians/faq.html#anchor_1529601728440
6. Gupta A, Ananthakrishnan AN. Economic burden and cost-effectiveness of therapies for Clostridiodes difficile infection: a narrative review. Therap Adv Gastroenterol. 2021;14:17562848211018654. doi:10.1177/17562848211018654
7. Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376(4):305-317. doi:10.1056/NEJMoa1602615
8. Zama D, Bossù G, Leardini D, et al. Insights into the role of intestinal microbiota in hematopoietic stem-cell transplantation. Ther Adv Hematol. 2020;11:2040620719896961. doi:10.1177/2040620719896961