Which Antibiotics Raise C. Diff Risk Most? Jason Pogue, PharmD

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In the past 2 decades, clinicians in the US have targeted specific broad-spectrum antibiotics—such as fluoroquinolones and clindamycin—to help mitigate patients' risk of developing Clostridioides difficile (C. diff), said Jason Pogue, PharmD, a clinical professor in the Department of Clinical Pharmacy at the University of Michigan College of Pharmacy and an infectious diseases clinical pharmacist at Michigan Medicine, in an interview with The American Journal of Managed Care^®.

He also pointed to limiting third-generation cephalosporins, naming these as 3 of the antibiotic classes that carry the highest C. diff risk for patients. C. diff is often associated with antibiotic use, and that risk increases the longer a patient remains on antibiotics, an area Pogue said clinicians can still take action to reduce.¹

"Regardless of which agent I choose, there's going to come a C. diff risk for that," he explained. "One of the things that I can do to try to limit that, in addition to avoiding some of those agents we already talked about, is that once they've hit the duration of therapy they need for a given disease state, which is very commonly 7 days or less, we can stop the antibiotics at that point."

Patients prone to recurrent C. diff, a population in which antibiotic exposure is a major precipitating factor, are at further increased risk, Pogue said, making treatment duration and antibiotic selection even more critical in this group.

"In addition to limiting the duration of therapy, this is going to be the population that we need to be very aggressive in, with regard to deescalation, making sure that we avoid some of those highest-risk antibiotics," he explained. "As well as—even with ones that are lower risk—we want to narrow that therapy as much as we possibly can in order to decrease the chance that we're messing with that microbiome in a way that's going to give C. diff the ability to overgrow and cause disease for our patients."

References

1. About C. diff. CDC. May 13, 2026. Accessed September 14, 2026. https://www.cdc.gov/c-diff/about/index.html