Higher metronidazole MIC linked to increased risk for clinic
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.

Clinical studies have demonstrated inferior cure rates when metronidazole (MTZ) is used to treat Clostridioides difficile infection (CDI). We hypothesized that a newly identified, heme-inducible form of reduced MTZ susceptibility in C. difficile leads to higher odds of initial clinical failure in patients with CDI treated with MTZ.

This multicenter cohort study included adults diagnosed with CDI. C. difficile isolated from stool samples underwent agar dilution MTZ susceptibility testing with incorporation of fresh heme. Blinded investigators reviewed medical records for initial clinical failure and other relevant clinical variables. Classification and regression tree (CART) analysis was used to identify the MTZ minimum inhibitory concentration (MIC) breakpoint that was predictive of initial clinical failure. Results were confirmed using univariate and multivariable logistic regression analyses to account for potential confounders.

-- Of the 356 patients included, 72% received MTZ-based therapy and 27% experienced initial clinical failure. CART analysis identified an MTZ MIC more than 1 µg/mL above which patients had a higher rate of initial clinical failure.

-- MTZ MICs ranged from 0.25 to 8 µg/mL (MIC50/90 = 0.25/2 µg/mL), and approximately 18% of isolates had MTZ MICs more than 1 µg/mL.

-- In multivariable analysis, an MTZ MIC more than 1 µg/mL was an independent predictor of initial clinical failure in patients receiving an MTZ-based treatment regimen (odds ratio, 2.27).

Conclusively, using a reproducible method to determine C. difficile MICs to MTZ, a breakpoint of more than 1 µg/mL identified patients at higher risk of initial clinical failure.

Source: https://academic.oup.com/ofid/article/8/8/ofab365/6317718