Current guidelines suggest limiting metronidazole (MTZ) use due to increased treatment failures in patients with Clostridioides difficile infections (CDI). We hypothesized that an increase in the minimum inhibitory concentration (MIC) of MTZ to C. difficile may contribute to these poor response rates. The objective of this study was to examine clinical response rates in patients with CDI based on MTZ MIC and stratified by receipt of MTZ treatment.
Clostridioides difficile-positive stool samples collected from 2017 to 2018 as part of routine care at two hospital systems in Houston, Texas were collected for MIC determination at 24 h to MTZ by broth microdilution following incorporation of 5 mg/L of hemin. The primary outcome was initial clinical success by Day 7 of treatment in those with MICs ≥1 vs. <1. Results were stratified based on receipt of MTZ within 48 hours of diagnosis. Study objectives were tested using χ 2 and multivariable logistic regression analyses.
A total of 235 C. difficile samples were included, of which 73 (31%) had an MTZ MIC ≥1. Overall, 72% received MTZ within the first 48 hours. Clinical success rates differed based on disease severity (77% in nonsevere, 64% in severe/fulminant; P = 0.03) and infecting ribotype (52% in RT 027, 75% in non-RT 027; P = 0.014). In patients with MTZ receipt, clinical success rates were higher in patients infected with strains with an MTZ MIC < 1 (76%) compared with those with an MIC ≥1 (60%; P = 0.031). The difference in initial clinical success was not different in those that did not receive MTZ (78% for MIC <1 vs. 65% for MIC ≥1, P = 0.28). After controlling for disease severity, treatment failure was higher in patients infected with strains with an MTZ MIC ≥1 and treated with MTZ (OR 2.1; 95% CI, 1.01–4.35; P = 0.048) but not for those with an MIC ≥1 treated with other therapies (OR 1.9; 95% CI, 0.62–5.6; P = 0.27).
This study provides the first preliminary evidence of an association between reduced metronidazole susceptibility and decreased clinical success rates. Larger studies are warranted to validate these findings.
All Authors: No reported Disclosures.