Current national guidelines suggest limiting metronidazole (MTZ) use due to increased treatment failures in patients with Clostridioides difficile infections (CDI). However, the reason for these increased failure rates is unclear. We hypothesized 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 who received MTZ monotherapy vs. other therapies stratified by MTZ susceptibility.
Stool samples that tested positive for C. difficile (2017–2018) were collected from two large academic hospital systems in Texas. C. difficile was isolated from stool and visually screened for growth on heme-containing agar plates with MTZ at 2 mg/L (defined as reduced susceptibility). Blinded investigators reviewed electronic medical records to identify the treatment received and determine clinical success or failure for each patient. Treatment failure rates were assessed in patients that received MTZ monotherapy vs. other therapies stratified by MTZ susceptibility. Results were analyzed using multivariate logistic regression analysis.
A total of 172 C. difficile isolates were included of which 55.8% displayed reduced susceptibility to MTZ. Clinical success rates with MTZ varied based on disease severity (mild-moderate: 80.4%; severe/severe-complicated: 64%). Treatment success rates were higher in patients infected with MTZ susceptible isolates (88.4%) compared with those infected with isolates showing reduced MTZ susceptibility (60.5%; P = 0.004.) In multivariate logistic regression after controlling for disease severity, patients infected with strains displaying reduced MTZ susceptibility and treated with MTZ were more likely to experience treatment failure compared with patients with susceptible isolates (OR = 6.8; 95% CI:1.96–23.8; P = 0.003). In patients given non-MTZ-based therapies, reduced susceptibility to MTZ was not predictive of failure to other treatments.
This is the first report to demonstrate that increased clinical failure rates for MTZ monotherapy are associated with reduced susceptibility to MTZ.
K. Garey, Summit Therapeutics: Collaborator, Research support.