Originally published by our sister publication Infectious Disease Special Edition
The Screening and Targeted Prophylaxis for Clostridioides difficile infection (STOP-CDI) protocol, developed at the University of Pennsylvania, resulted in a substantial reduction in healthcare-associated CDI among patients screened, reported Matthew Ziegler, MD, an assistant professor of medicine (infectious diseases) at the Hospital of the University of Pennsylvania, in Philadelphia. The intervention also was associated with fewer stools and shorter hospital length of stay.
“At our hospital, we have struggled with hospital-onset C. diff in our immunocompromised patient population for some time, and this does not seem to be an isolated phenomenon,” Dr. Ziegler said at IDWeek 2024, in Los Angeles. “Other centers have also reported very high rates of hospital-onset C. diff, with up to one-third of allogeneic stem cell transplant patients developing it during their stay.
“We hypothesized that the majority of patients coming into our hospital and developing C. diff might be developing it from a colonizing strain, rather than acquisition within the hospital, and we were interested in potential interventions to reduce or prevent that transition from colonization to infection state, particularly with an emphasis on patients coming in for highly immunosuppressing therapies where antibiotic receipt is likely,” Dr. Ziegler explained.
The STOP-CDI protocol was developed to screen these patients for colonization with C. difficile, allowing for targeted prophylaxis to reduce unneeded antibiotic exposure in non-colonized patients while also preventing spread to non-colonized patients with prophylaxis, isolation and enhanced cleaning.
Beginning in November 2021, study investigators prospectively identified eligible patients: those admitted for solid organ transplants (SOTs) or with planned admission for hematologic malignancies, including autologous stem cell transplant, chimeric antigen receptor T-cell therapy or leukemia treatment. If asymptomatic, these patients would undergo a rectal swab or stool sampling on or before hospital day 3; if they were colonized with C. difficile, they were isolated with contact precautions and received oral vancomycin prophylaxis.
The analysis compared two cohorts:
- The STOP-CDI exposed cohort included any patient who was screened, with either a positive or negative result, after rollout of the intervention in November 2021 through December 2023.
- The unexposed cohort included historical controls from November 2019 through October 2021, who would have met all the eligibility criteria for STOP-CDI screening.
“Our primary outcome was hospital-onset C. diff, defined as a positive result after hospital day 3, including both immunoassay and molecular positive tests,” Dr. Ziegler said. “Our secondary outcomes included 90-day CDI, microbiologic VRE [vancomycin-resistant Enterococcus] infection, stool output, length of stay and in-hospital mortality.”
During the study period, 696 patients were screened and matched to a cohort of 1,447 patients in the historical control period. The intervention and control groups were matched closely by general demographics and exposure to medications, including proton pump inhibitors, fluoroquinolones, broad-spectrum beta-lactamase antibiotics and cephalosporins.
“In our intervention cohort, we identified 11% of the patients we screened as colonized with C. diff,” Dr. Ziegler said. “But there were only six cases of hospital-onset C. diff infection. That’s a 0.8% predicted probability of C. diff onset compared with our controls of 5.6%. This results in an odds ratio of 0.14 for hospital-onset C. diff. We estimated that the intervention prevented 33 cases of C. diff during the study period, and the number needed to screen to prevent one case is 21.”
In the study’s secondary outcomes, there was no difference in VRE overall or at 90 days, but there was a modest reduction in hospital length of stay of 2.4 days in the intervention cohort. “There was also a reduction in daily stool count of roughly 15%,” Dr. Ziegler said.
Because the study population included both cancer and transplant patients, the investigators also further assessed whether the intervention was more beneficial in one group or the other. They found that the rate of hospital-onset C. diff was much higher in the oncology patients than the SOT patients, leading to different numbers needed to screen. “In our oncology group, the number needed to screen to prevent one case was 16, as opposed to 94 in our SOT population,” Dr. Ziegler said. “The colonization rates in the two populations were similar, but the absolute impact of this intervention was much larger in oncology.”
Dr. Ziegler noted that there were some limitations to the study, including a nonrandomized study design and the possibility of unadjusted confounders. “We also did open a new hospital building during the intervention cohort, and unfortunately, did not do any environmental sampling to determine the impact of prophylaxis on environmental contamination,” he said.
“This is an interesting cohort/intervention study, with potentially impressive results. However, it appears that some CDIs were diagnosed using molecular tests, and these are known to overidentify true infections,” said Mark Wilcox, MD, a professor of medical microbiology and the Sir Edward Brotherton Chair of Bacteriology at the University of Leeds, as well as the lead on CDI for Public Health England and the National Clinical Director of Antimicrobial Resistance & Infection Prevention and Control for the National Health Service England. “Also, a new hospital building was opened for the intervention cohort during the study, which has previously been associated with reducing CDI rates.”
More data are needed. “We need a randomized study with robust definitions for CDI, and better control of potential confounders, to determine if screening and prophylaxis can truly reduce CDI rates without unintended consequences, such as VRE selection, which is a known risk in hem/onc patients,” recommended Dr. Wilcox, who is also a member of the Infectious Disease Special Edition editorial advisory board.
Dr. Wilcox reported relationships with Abbott Laboratories, Actelion, Alere, Astellas, Astra-Zeneca, bioMerieux, Bayer, Cerexa, Cubist, Durata, MedImmune, Merck, Motif Biosciences, Nabriva, Optimer, Paratek, Pfizer, Roche, Sanofi-Pasteur, Seres, Summit and Synthetic Biologics Da Volterra. Dr. Ziegler reported no relevant financial disclosures.
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