Clostridioides difficile (C. diff) is a leading cause of hospital associated infections nationally, and a significant burden at UNC Hospitals. Patients with C. diff infections (CDI) frequently experience recurrent or prolonged diarrhea following antibiotic exposures. They are also at a high risk for adverse outcomes and prolonged hospitalizations, with high rates of recurrent disease and hospital readmission.
Despite prior efforts that reduced infection rates by 50%, through education, antibiotic decision support, and diagnostic stewardship, enhanced intervention strategies are needed to address the complex, debilitating, and often costly care of recurrent CDI (rCDI). An internal data analysis at UNC Health revealed discrepancies in reported rCDI cases versus actual patient encounters, demonstrating the need for more accurate tracking and patient-centered interventions. And while new therapies can interrupt recurrent infections, timely access is limited by inefficiencies in existing care models.
A cross-disciplinary project led by Thomas Holowka, MD, PhD, fourth-year fellow (PI) and Luther Bartelt, MD, DTM&H, associate professor (co-PI), focuses on active surveillance, expedited evaluation by experts, and improved access to novel therapies. The two are piloting a service embedded within the ID clinic overseen by Claire Farel, MD, MPH, at Eastowne that is expected to diminish wait times for patients, and facilitate a more accurate diagnosis through a detailed patient history and exam.
Active surveillance starts with a C. diff dashboard maintained by the Carolina Antimicrobial Stewardship Program. Electronic medical records for patients who test positive for C. diff are reviewed daily by Research Assistant Trieu-Vi Khuu to identify patients with a prior episode within the prior 6 months, meeting the definition of rCDI. For identified rCDI patients, Dr. Holowka coordinates a clinic referral using a newly generated Epic pathway. Patients are scheduled for expedited expert evaluation and non-procedural management in the ID clinic at Eastowne.
“The clinic is now fully operational, and we’ve seen over 40 new patients for recurrent C. diff, referrals from within and outside of UNC,” said Dr. Holowka. “So far, we’ve been able to reduce wait times for new patients by about a month, and successfully prescribed novel microbiota-targeted live biotherapeutic products to more than a dozen patients.”
Appointments within 30 days are prioritized, with patient visits at the dedicated rCDI clinic at the Eastowne outpatient facility. If an in-person visit cannot be scheduled promptly, telemedicine options are utilized to expand accessibility. The service has already identified stewardship opportunities for earlier discontinuation of antibiotics, with ID expertise, and a pathway towards standardizing the role of novel microbiota-directed therapies to insure they are being responsibly prescribed to the patients who would benefit most. Patients undergoing treatment receive follow-up care within 30-90 days to evaluate rCDI resolution, defined as the absence of symptoms without ongoing antimicrobial treatment.
Leveraging Partnership with Gastroenterology
Funded by a Pilot Innovation Award, the project builds on Dr. Holowka’s experience as an ID Fellow (ID Pathogenesis T32) pursuing translational biomedical research under the mentorship of Dr. Bartelt. The project also leverages a partnership with gastroenterology. Since 2013, Dr. Sarah McGill in gastroenterology has provided access to microbiota-directed therapies for rCDI at UNC with a statewide referral base. This highly successful therapy was previously only accessible through colonoscopic delivery, requiring additional workflows and scheduling of procedure rooms. Now, pharma alternatives to fecal transplants are enabling referrals to shift to infectious diseases, creating new routes for expedited appointments. Dr. McGill and the gastroenterology team continue to coordinate colonoscopic intestinal microbiota delivery when appropriate. In select cases, the ID rCDI clinic has been able to refer patients with concurrent inflammatory bowel disease directly to the IBD specialty clinic. These new work flows are optimizing the high level of expertise available at UNC Health.
CDI is the result of an overgrowth of C. diff bacteria, when antibiotics have depleted the good bacteria that live in the gut, and in patients with recurring CDI, the damaged intestinal microbiota fails to recover. Since 2017, intestinal microbiota transplant with bacteria derived from human donor feces has been a recommended investigational therapy for patients with multiple CDI recurrences. But in the past two years, novel FDA-approved microbiota-directed therapies have become available, alternatives to costly endoscopic interventions and procedural risks. These therapies are approved for use after a single recurrence, and have efficacy for prevention of further recurrences as high as 70%.
“C diff is an ever-present risk in our hospitals and in the community. It leads to a lot of patient misery and healthcare expenditures. We are still accumulating patient outcomes and satisfaction data, but the process is certainly getting to patients with recurrent C. diff much sooner,” said Dr. Bartelt. “We hope the new clinical workflow will further improve care for rCDI, that can be expanded to encompass all high-risk CDI patients, including patients at earlier stages of CDI diagnosis.”
Preliminary data from the pilot will be used to apply for additional internal and external funding sources that could support further research activities. Future external funding could also be utilized to expand the clinic for investigational treatment of patients with intestinal conditions other than rCDI, to ultimately establish UNC as a leader in the field of microbiota-targeting therapies.