A pproximately 4% of hospitalized patients who were colonized with toxigenic Clostridioides difficile progressed to hospital-onset C. difficile infection (HO-CDI) and showed key risk factors for progression, according to a recent study.

Preventing HO-CDI is challenging because of the widespread nature of C. difficile colonization, the difficulty in distinguishing colonization from true infection, and the necessity for broad-spectrum antibiotics in critically ill patients with overlapping risk factors.

To better understand the incidence and risk factors for progression from C. difficile colonization to active infection, researchers conducted a nested case–control study of hospitalized adults with a positive C. difficile polymerase chain reaction test on admission to the University of California, Davis Medical Center, from 2017 through 2020 (Infect Control Hosp Epidemiol 2025 Feb 24. doi:10.1017/ice.2025.4).

CDI was defined as pseudomembranous colitis on colonoscopy, histopathologic diagnosis, or three or more episodes of loose stools within 24 hours without any other etiology; asymptomatic colonization was defined as a positive PCR rectal swab without CDI symptoms. Patients with colonization who progressed to HO-CDI were matched 1:3 to colonized patients with no progression.

image

A total of 321 patients were included in the final cohort (mean age, 64 years; 45% female; average hospital length of stay, 11.9 days). Most patients, 70.1%, were admitted from home; 61.7% had prior hospitalization within six months; and 37.1% were admitted to the ICU. During hospitalization, 78.8% of the patients received antibiotics.

Progression to HO-CDI was reported in 69 patients, for an estimated incidence of 4.2%.

Significant risk factors for progression from colonization to HO-CDI were cirrhosis (adjusted hazard ratio [aHR], 1.94), admission to the ICU (aHR, 1.76), malignancy (aHR, 1.88), receipt of prior antibiotics (aHR, 2.14), increasing number of at-risk antibiotic classes (aHR per additional class, 2.17), and previous hospitalization within six months (aHR, 2.72).

The use of immunosuppressants and proton pump inhibitors was not a statistically significant predictor. In addition, age—which often is considered a major risk factor for CDI—was not an independent predictor of progression among colonized patients.

According to Josh Clement, PharmD, the study’s lead author, the most surprising result was that opioid use was associated with a significantly lower risk for progression to HO-CDI (aHR, 0.34).

“This contradicts previous studies that suggested opioid-induced changes in gut motility might increase CDI risk,” said Dr. Clement, an infectious diseases clinical pharmacy manager at the Mount Sinai Hospital, in New York City. The results also reinforce the fact that while colonization with C. difficile may be common, it is not always benign.

“What stood out to us was how ICU admission was a particularly strong predictor of HO-CDI,” he told Gastroenterology & Endoscopy News. “This highlights the need for ICU-specific prevention strategies, including stricter antibiotic oversight and enhanced infection control measures.”

Nearly 80% of colonized patients received antibiotics, which suggests that de-escalation efforts are needed in this population. Antibiotic stewardship can be inherently challenging in ICU settings due to the high acuity of illness and the frequent use of broad-spectrum antibiotics. Still, unnecessary antibiotic exposure can be reduced while maintaining high-quality ICU care. Dr. Clement identified several key approaches:

  • Set clear antibiotic guidelines for initiation, duration and de-escalation, with daily reviews by stewardship teams.
  • Implement “handshake stewardship,” whereby stewardship pharmacists and physicians engage directly with ICU teams to provide real-time recommendations. This collaborative, nonpunitive approach improves adherence to stewardship interventions.
  • Reduce high-risk antibiotics such as fluoroquinolones, cephalosporins and clindamycin when safer alternatives are available.
  • Strengthen infection control practices, including strict hand hygiene and environmental cleaning, to minimize C. difficile transmission.

Dimitri Drekonja, MD, MS, the chief of the Infectious Disease Section at the Minneapolis VA, who was not involved with the study, agreed. “We get nervous in the ICU because many people are going in and out of rooms,” he said. “Every time you go in or out of a room is a chance to perform hand hygiene, but it’s also a chance to not perform hand hygiene.”

Dr. Drekonja commended the authors for adding nuance to the overall body of knowledge of C. difficile colonization and progression to CDI, and indicated that the decision to implement enhanced monitoring and prevention efforts—particularly in the ICU—is ultimately decided by an individual hospital’s needs.

“If a hospital has high rates of C. difficile colonization,” he said, “then [these methods] are something you can explore if you have the infrastructure to make sure they’re implemented properly.”

—Paul Basilio

Drs. Clement and Drekonja reported no relevant financial disclosures.

This article is from the June 2025 print issue.