Higher metronidazole MIC linked to increased risk for clinical failure in C. difficile
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Reduced susceptibility to metronidazole was associated with decreased clinical response rates in patients with Clostridioides difficile infection, according to a study published in Open Forum Infectious Diseases.
“Declining clinical response rates removed metronidazole (MTZ) from guidelines as a preferred agent to treat C. difficile infection (CDI),” Kevin W. Garey, PharmD, MS, FASHP, FIDSA, professor of pharmacy and chair of the department of pharmacy practice and translational research at the University of Houston College of Pharmacy, told Healio. “The reason for this declining response rate was not known.”
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Garey and colleagues performed a multicenter cohort study of adults diagnosed with CDI between 2017 and 2018 at 14 hospitals in Houston. They tested C. difficile isolates from stool samples for MTZ susceptibility and reviewed medical records for indications of clinical failure.
They used classification and regression tree (CART) analysis to identify the MTZ minimum inhibitory concentrations (MIC) breakpoint that was predictive of initial clinical failure.
Of the 356 patients included in the study, 72% received MTZ-based therapy and 27% experienced initial clinical failure, according to Garey and colleagues. CART analysis identified that patients had a higher rate of initial clinical failure with an MTZ MIC of greater than or equal to 1 µg/mL, they reported.
Further, an analysis showed that an MTZ MIC of greater than or equal to 1 µg/mL was an independent predictor of initial clinical failure in patients receiving a MTZ-based treatment regimen (OR = 2.27; 95% CI, 1.19-4.34).
“This is the first study to demonstrate that C. difficile-reduced susceptibility to metronidazole is associated with decreased clinical response rates,” Garey said.
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