Balancing Antibiotic Efficacy and C. Diff Risk: Keith Kaye, MD, MPH

Patients currently taking an antibiotic, or in the month after finishing one, are up to 10 times more likely to develop Clostridioides difficile (C. diff) infection, and longer courses of antibiotics can potentially double that risk.¹

This is why hospitals, researchers, and clinicians have worked together to shorten antibiotic treatment courses in an attempt to curb the risk of patients developing C. diff while on or after taking an antibiotic, Keith Kaye, MD, MPH, chief of the Division of Allergy, Immunology, and Infectious Diseases and professor of medicine in the Department of Medicine at Rutgers Robert Wood Johnson Medical School, said in an interview with The American Journal of Managed Care^®.

"When I started as a trainee in the '90s, and then as an attending beginning in the early 2000s, we would initially treat for much longer durations of therapy—14 or 21 days for ventilator-associated pneumonia," he explained. "Now we're down to 7 days across the board."

Kaye described this balance as a double-edged sword: effective antibiotic therapy on one side and C. diff risk and microbiome disruption on the other. Any antibiotic can carry a risk of C. diff, although broader-spectrum agents that disrupt the gut microbiome to a greater degree can raise that risk further. Kaye said there are still several precautions clinicians can take when prescribing antibiotics for infections.

"I think the best way to combat this is to optimize therapy for patients who need treatment, so avoid treating colonization, optimize therapy, and then treat with as short a duration as possible," he said.

For most infections, Kaye said treatment now runs 7 days or less, with some exceptions. He added that determining which patients truly need antibiotics, dosing aggressively but safely, and minimizing duration to the shortest effective course is, in his view, the most stewardship-conscious approach to treating serious infections while also minimizing C. diff risk.

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Reference

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