Targeted C Diff Screening, Prophylaxis Reduces Hospital-Onset Infection

New research is shedding light on the potential benefits of implementing a targeted C.difficile screening and prophylaxis intervention for high-risk immunocompromised patients, highlighting subsequent reductions in hospital-onset infection, length of stay, and symptoms.¹

The screening and targeted prophylaxis (STOP) intervention was implemented over a 2-year period and focused on patients newly admitted for solid organ transplant and planned oncology treatment admissions for autologous stem cell transplant, CAR-T, and leukemia treatment, populations known to be disproportionately affected by CDI but who may not benefit from universal primary prophylaxis approaches. Compared with historical controls in the 2 years prior to implementation of the intervention, STOP was effective at reducing hospital-onset CDI and associated symptoms.^1,2

“Prior studies have attempted eradication among asymptomatic carriers, but none have been designed to specifically halt the progression from asymptomatic colonization to CDI among vulnerable populations during their period of highest risk,” Matthew Ziegler, MD, an assistant professor of medicine (infectious diseases) at the Hospital of the University of Pennsylvania, and colleagues wrote.¹ “In comparison to prior literature, our work has notable differences.”

To better understand the potential for prophylactic antibiotics to reduce hospital- onset CDI and the adverse effects of prophylaxis, investigators implemented a novel strategy in which they preemptively identified patients at high risk of CDI during inpatient admissions with planned intensive immunosuppression and antimicrobial exposures. Patients admitted for solid organ transplant, autologous stem cell transplant, CAR-T, or treatment for leukemia were screened for colonization with C.difficile, with colonized patients placed in contact isolation and advised to start anti-C.difficile antibiotic prophylaxis.¹

The primary study outcome was the incidence of hospital-onset CDI, defined as a positive C.difficile test after hospital day 3. To assess the effect of the STOP intervention on both C.difficile testing and incident hospital-onset CDI, comparison was made to historical controls in the 2 years prior to implementation of the intervention, both unweighted and weighted by treatment category and separately by treatment category and severity of illness.¹

Between November 2021 and December 2023, 696 patients were screened for C.difficile, among whom 11.1% (n = 77) were found to be colonized and received the prophylactic intervention.¹

Investigators noted the rate of hospital-onset CDI was 0.88% in the intervention cohort compared to 3.7% in the unweighted historical control and 5.6% in the treatment-weighted control cohort, representing a 4.8% absolute reduction in probability of hospital-onset CDI (95% credible interval [CrI], 3.4% to 6.2%) from the STOP intervention. This absolute risk reduction corresponds to an odds ratio (OR) of 0.15 (95% CrI, 0.06 to 0.30) in STOP cohort subjects, compared to weighted historical controls.¹

Among patients screened, 3.0% developed CDI within 90 days of their index admission. Among those who were identified to be colonized, 7.8% subsequently had a positive test for CDI within 90 days of their index admission.¹

Investigators observed significant reductions in 90-day CDI (OR, 0.40; 95% CrI, 0.25 to 0.64), stool output (incidence rate ratio, 0.84; 95% CrI, 0.77 to 0.92), and length of stay (-2.5 days; 95% CrI, -3.4 to -1.5) in the intervention group. Of note, there was no detected difference in VRE infection (OR, 0.77; 95% CrI, 0.33 to 1.75) or mortality (OR, 0.44; 95% CrI, 0.11 to 1.49).¹

“A targeted screening and prophylaxis intervention for the prevention of C.difficile infection among immunocompromised patients was associated with a significant reduction in HO-CDI and symptoms associated with CDI,” investigators concluded.¹ “Future work with randomized trial design would help to confirm these findings, assess the potential for this intervention to reduce transmission of C.difficile within healthcare units, and to target additional patient populations who may benefit from this strategy.”

References

1. Ziegler MJ, Anesi J, Tolomeo P, et al. Screening and Targeted Prophylaxis for Clostridioides difficile Infection: STOP-CDI. Clin Microbiol Infect. doi:10.1016/j.cmi.2025.08.004

2. US Centers for Disease Control and Prevention. About C. diff. December 18, 2024. Accessed August 21, 2025. https://www.cdc.gov/c-diff/about/index.html