Why Does Colonization Become Active C. difficile?
July 15, 2025
By Carol A. Kemper, MD, FIDSA
Source: Clement J, Barlingay G, Addepalli S, et al. Risk factors for the development of Clostridioides difficile infection in patients colonized with toxigenic Clostridioides difficile. Infect Control Hosp Epidemiol. 2025;Feb 24:1-7. doi: 10.1017/ice.2025.4. [Online ahead of print].
These authors performed a nested case-control study to identify risk factors for the progression from Clostridioides difficile (CD) colonization to active infection (CDI) in hospitalized persons. Based on data demonstrating the benefit of screening in the reduction of CD transmission in the hospital, the University of California Davis Medical Center performs universal screening for CD using perirectal polymerase chain reaction (PCR) for all admissions. They preemptively isolate all patients with CD colonization.
To identify risk factors for progression from colonization to active infection, patients who developed active CDI were matched 1:3 with those who did not. Patients were excluded from the study if they had a previous history of CDI, neutropenia, or hospitalization within 24 hours. Active CDI was diagnosed based on both symptoms of three or more loose stools within 24 hours and a positive CD toxin enzyme immunoassay (EIA) test, pseudomembranous colitis on colonoscopy, or histopathologic evidence of active CDI. Hospital-onset CDI (HO-CDI) was defined as occurring after the first three days of hospitalization.
From 2017 to 2020, 57,468 admissions to the hospital were screened, of whom 2,150 (3.7%) were perirectal PCR-positive for toxigenic CD organism. Among these, 109 patients were diagnosed with CDI, including 69 cases of HO-CDI. The median time to diagnosis of CDI was 7.4 days. The average age was 64 years, and the average hospital length of stay was 11.9 days. All-cause mortality during hospitalization was significantly higher for HO-CDI infection cases compared with controls (15.9% vs. 6.3%, P = 0.011). Bivariate analysis showed that HO-CDI cases were more likely older (> 65 years of age), admitted from healthcare facilities, admitted to the intensive care unit (ICU) at baseline, and hospitalized within the previous six months. They also were more likely to have cirrhosis (17.4% vs. 7.1%, P = 0.01), to have diabetes (50.7% vs. 30.2%, P = 0.002), to have malignancy (21.7% vs. 7.9%, P = 0.001), to be immunosuppressed, to have received immunosuppressives prior to hospitalization, to have received antibiotics within the three months prior to hospitalization (76.8% vs. 43.8%, P < 0.001), or to have received “at-risk” antibiotics during the hospital stay (60.9% vs. 23.8%, P < 0.001). Multivariate analysis confirmed that the risk of progression to HO-CDI was significantly associated with cirrhosis, hospitalization within the prior six months, ICU admission, malignancy, and an increased number of at-risk antibiotics. Proton pump inhibitor use was not significantly associated with the progression to CDI.
Most of us would recognize these previously mentioned risk factors for progression to active CDI, with the possible exception of cirrhosis. It is of interest that 70% of the patients in this cohort were admitted from home, although 62% had been hospitalized within the previous six months. Increasingly, CDI is recognized as a community-acquired pathogen. Our facility in Mountain View, CA, similarly screens admissions with perirectal PCR in an effort to preemptively isolate those with colonization and reduce the risk of hospital transmission. Rather than universal screening, we have chosen to focus our efforts on those patients at higher risk for CD colonization, including those with a history of CDI (35% colonized), those receiving dialysis (19% colonized), and those admitted from a skilled nursing facility or long-term acute care facility (14% colonized). Even with this, only 20% to 30% of hospitalized patients who develop HO-CDI had a positive CD PCR on admission, and only ~5% of those with colonization on admission progress to active HO-CDI.
The problem becomes how do we identify that one-in-20 individual out of all of those who are colonized and possibly at risk, who will go on to develop HO-CDI? What is it about that 5% of persons with colonization that puts them at particular risk for progression to active CDI during their hospitalization? If prevention or intervention is to be effective, we need a better way to identify that individual. It does not make sense to give everyone at risk preemptive oral vancomycin if only 5% might benefit.
Carol A. Kemper, MD, FIDSA, is Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation.
These authors performed a nested case-control study to identify risk factors for the progression from Clostridioides difficile colonization to active infection in hospitalized persons.
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