Colonization vs Infection: Rethinking C. Diff Prevention

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When a hospitalized patient develops Clostridioides difficile (C diff) infection, the case is often assumed to have been acquired in the hospital, but that assumption may not hold for some high-risk patients.

Some of these patients arrive at the hospital already colonized with C diff, and the treatments they receive there can shift them from colonization to infection, Senu Apewokin, MD, associate professor and founding director of the Transplant Infectious Disease Service at the University of Cincinnati College of Medicine, said in an interview with The American Journal of Managed Care^® at IDWeek 2026, held October 21-24 in Washington, DC.

Under the current approach, patients who develop C diff 48 hours after admission are considered to have a hospital-acquired infection, with the assumption that it was transmitted by a health care worker, another patient, or the hospital environment, he explained.

“I think in truth, there are some new emerging data and evidence that suggests that some of these people come into the hospital with C diff, but then the interventions that we start is what transition[s] them from colonization to an infection,” Apewokin said.

In the intensive care unit (ICU), for instance, patients may arrive colonized, receive a number of antibiotics that disrupt the microbiome, and then develop C diff infection, he said. Other infectious disease experts have pointed to antibiotic-driven microbiome disruption as a key factor in C. diff risk.¹ Patients receiving chemotherapy often follow a similar pattern, as chemotherapy wipes out their humoral immunity, Apewokin added.

“In that setting, it’s not a hospital-acquired infection. It’s more a transition from colonization to infection,” he said.

Yet current approaches to C diff prevention don’t distinguish between these scenarios.

“We lump them all together and treat them all the same,” Apewokin said. “I think we need more data to tease out whether there should be a distinction.”

Gathering that evidence is its own challenge. Many high-risk patients are not enrolled in clinical trials because their other medical issues could confound the results, even though they sometimes need these interventions, he said. C diff trials require thousands of patients and substantial funding, and it will take years for the data to accumulate.

“Before we get actual evidence, I think payers should really think, is there a possibility of still providing access to some of these interventions even when we’re trying to get a little evidence?” Apewokin said.

References

1. McCrear S. Balancing antibiotic efficacy and C. diff risk: Keith Kaye, MD, MPH. AJMC. September 2026. Accessed October 23, 2026. https://www.ajmc.com/view/balancing-antibiotic-efficacy-and-c-diff-risk-keith-kaye-md-mph