Infectious Disease

Higher MICs of metronidazole associated with an increased risk of clinical failure in C. difficile

August 14, 2021

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According to a study published in the Open Forum Infectious Diseases, decreased sensitivity to metronidazole was associated with decreased clinical response rates in patients with Clostridioides difficile infection.

Kevin W. Garey

“Declining clinical response rates have removed metronidazole (MTZ) from guidelines as the preferred treatment for C. difficile infection (CDI).” Kevin W. Garey, PharmD, MS, FASHP, FIDSA, Professor of Pharmacy and chair of the Department of Pharmaceutical Practice and Translational Research at the University of Houston’s College of Pharmacy, said Healio. “The reason for this falling response rate was not known.”

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Decreased susceptibility to metronidazole is associated with decreased clinical response rates in patients with C. difficile. Source: Adobe Stock.

Garey and colleagues conducted a multicenter cohort study of adults diagnosed with CDI in 14 Houston hospitals between 2017 and 2018. They tested C. difficile isolates from stool samples for MTZ susceptibility and reviewed medical records for signs of clinical failure.

They used classification and regression tree analysis (CART) to identify the MTZ limit of minimum inhibitory concentrations (MIC) that predicted initial clinical failure.

Of the 356 patients enrolled in the study, 72% received MTZ-based therapy and 27% experienced initial clinical failure, according to Garey and colleagues. The CART analysis indicated that patients with an MTZ MIC greater than or equal to 1 µg / ml had a higher rate of initial clinical failure, they reported.

In addition, an analysis showed that an MTZ MIC greater than or equal to 1 µg / ml was an independent predictor of initial clinical failure in patients receiving an MTZ-based treatment regimen (OR = 2.27; 95% CI 1 , 19-4.34).

“This is the first study to show that reduced susceptibility to metronidazole caused by C. difficile is associated with reduced clinical response rates,” said Garey.

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