This inflammation of the colon poses a substantial burden to patients and the health care system.
Clostridioides difficile infection (CDI) affects nearly 500,000 patients each year, costing the health care system several billion dollars.1 Infection is associated with substantial morbidity, including the risk of recurrent infection. Recurrent CDI (rCDI) occurs in approximately 10% to 30% of patients after a first episode, with the risk of recurrence increasing with subsequent episodes.1
In 2021, the American College of Gastroenterology, the European Society
of Clinical Microbiology and Infectious Diseases, and the Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA) all published guideline updates with increased emphasis on therapies
that have been shown to decrease the risk of rCDI.2-4 Notable updates include preference for use of bezlotoxumab and fidaxomicin in patients at high risk for rCDI, as well as recommendations for fecal microbiota transplantation (FMT) in patients with multiple episodes of rCDI.1-4 Although these therapies are clinically beneficial, they are associated with several barriers that may affect patient access and successful transitions of care.
Perhaps the most widely appreciated barrier to CDI therapies is affordability. Medication delays related to economic barriers are associated with rCDI and rehospitalization.5 Although affordability is a concern, especially with fidaxomicin (the average wholesale price is approximately $5000 per treatment course), insurance coverage may be increasing since the 2021 IDSA/SHEA treatment guideline update. One small study of 15 patients discharged with fidaxomicin in 2021 identified successful acquisition of fidaxomicin in 12 cases (80%), with all prescriptions covered by commercial insurance. Most (93%) patients had insurance co-payments of less than or equal to $50.6 However, this was a small analysis, and investigators indicated that the number of successful discharge prescriptions with fidaxomicin was higher than anticipated.
Several best practices can be considered to improve access to fidaxomicin. In the days prior to hospital discharge, a patient’s fidaxomicin formulary status and prescription insurance policy should be determined to confirm affordability and coverage. In many cases, prior authorizations may be necessary. In instances when an insured patient has a high co-pay, coupons avail- able on the manufacturer’s website may be helpful.6 Uninsured patients can use the manufacturer patient assistance program. Each of these efforts requires time for processing, which may delay patient access to treatment.
Similar access issues exist with bezlotoxumab in that predicting costs to the patient can be challenging. Patient assistance programs from the manufacturer are available but can delay time to administration, which is recommended to occur during antibiotic therapy.7 Coordination with outpatient infectious diseases providers can be beneficial to synchronize efforts with an outpatient infusion center and help manage the patient until time of bezlotoxumab administration.
Paired with cost challenges, availability of these therapies may be limited. Local pharmacies and postdischarge care facilities may not adequately stock fidaxomicin. Therefore, supply should be confirmed at the time of valuating patient affordability.8 Similar access concerns can be expected for bezlotoxumab and FMT when considering discharge of a patient with high-risk CDI to a postdischarge facility. Furthermore, the COVID-19 pandemic has likely complicated patient access to bezlotoxumab and/or FMT that would be planned for administration in health care settings.
For institutions with outpatient infusion centers, appointment availability or workflows may be limited in the setting of COVID-19 precautions. Procedures, such as colonoscopies, to administer FMT might be performed on a more restricted basis. This procedure is further complicated by concerns for transmission of SARS-CoV-2 in the stool and exposure risk via aerosolization to health care providers.9
A final barrier that may be underappreciated is lack of provider familiarity with these therapies.8 Bezlotoxumab is often reserved for patients at high risk for rCDI and is preferentially administered in the outpatient setting for reimbursement purposes. Therefore, some providers may have limited experience with or knowledge of this agent. This may lead to missed opportunities to identify candidates who may benefit from this therapy. Similar barriers may exist surrounding FMT, as the processes often require a gastroenterologist or an infectious diseases specialist.
There are numerous barriers associated with CDI management, including clinical, patient-related, and systemic barriers.8 One comprehensive resource that addresses these barriers is a guide for transitions of care developed by an expert multidisciplinary committee, including a case manager, CDI patient representative, gastroenterologist, and primary care provider. This guide, published in 2019 by the National Transitions of Care Coalition, summarizes strategies to prevent primary CDI, reduce the risk of rCDI, and mitigate the risk of CDI-associated readmissions.10 Pharmacist members of interdisciplinary care teams can play a variety of roles, including collaborative development of institutional treatment pathways, such as assisting with medication access, providing CDI-associated counseling, and considerations for transitions of care. A multidisciplinary approach with supportive infrastructure can help facilitate successful therapy access and transitions of care to patients.
About The Authors
Emily Drwiega, PharmD, BCIDP, BCPS, AAHIVP, is an infectious diseases pharmacy fellow at the University of Illinois at Chicago College of Pharmacy.
Monique R. Bidell, PharmD, BCPS, is a medical science liaison at Ferring Pharmaceuticals in Boston, Massachusetts.
1. McDonald LC, Gerding DN, Johnson S, 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. doi:10.1093/cid/cix1085
2. Johnson S, Lavergne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clin Infect Dis. 2021;73(5):e1029-e1044. doi:10.1093/cid/ciab549
3. Kelly CR, Fischer M, Allegretti JR, et al. ACG clinical guidelines: prevention, diagnosis and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278
4. van Prehn J, Reigadas E, Vogelzang EH, at al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;27(suppl 2):S1-S21. doi:10.1016/j.cmi.2021.09.038
5. Bunnell KL, Danziger LH, Johnson S. Economic barriers in the treatment of Clostridium difficile infection with oral vancomycin. Open Forum Infect Dis. 2017;4(2):ofx078. doi:10.1093/ ofid/ofx078
6. Fang N, Ha D, Dong K, et al. Successful fidaxomicin hospital discharges of adult patients with Clostridioides difficile infections post 2021 guidelines – are economic barriers finally coming down? Clin Infect Dis. 2021;ciab1061. doi:10.1093/cid/ciab1061
7. Zinplava. Prescribing information. Merck & Co Inc; 2016. Accessed June 10, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761046s000lbl.pdf
8. Khanna S, Lett J, Lattimer C, Tillotson G. Transitions of care in Clostridioides difficile infection: a need of the hour. Ther Adv Gastroenterol. 2022;15:17562848221078684. doi:10.1177/17562848221078684
9. Ianiro G, Mullish H, Kelly CR, et al. Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic. Gut. 2020;69(9):1555-1563. doi:10.1136/gutjnl-2020-321829
10. Interprofessional pathways for successful transitions of care in patients with Clostridioides difficile infection. Interprofessional Steering Committee, National Transitions of Care Coalition. 2019. Accessed June 10, 2022. https://media.primeinc.org/upload/PRIME%20CDiff%20Pathways%20 for%20Transitions%20of%20Care.pdf