# Minimum Inhibitory Concentration Increase in Clostridioides difficile Isolates from Patients with Recurrence: Results from a Retrospective Single-Centre Cohort Study

## TL;DR

This study found increased minimum inhibitory concentrations for some antibiotics in Clostridioides difficile isolates from patients with recurring infections, which may impact treatment outcomes.

## Contribution

The study reports MIC increases in C. difficile isolates from recurrent infections and links higher MIC to increased mortality.

## Key findings

- No resistance to vancomycin, metronidazole, and tigecycline was found, but all isolates showed ciprofloxacin resistance.
- Recurrent isolates showed 2- to 4-fold MIC increases for vancomycin, metronidazole, and tigecycline.
- Higher vancomycin MIC was associated with increased 28-day mortality in patients.

## Abstract

Antimicrobial susceptibility testing (AST) is not routinely performed for C. difficile infection (CDI); however, reports of antimicrobial resistance to various antibiotics have increased. This study aimed to assess the rate of antimicrobial resistance to four antimicrobials (vancomycin, metronidazole, tigecycline, and ciprofloxacin) to assess risk factors for antimicrobial resistance and evaluate MIC variation in patients with recurrence. Data from consecutive patients with CDI admitted to our institution between 1 January 2022 and 30 April 2023 were collected. We performed AST with gradient diffusion and NAAT to evaluate the presumptive presence of R027/NAP1 and toxin production genes. Antimicrobial susceptibility testing was performed on 108 available isolates. We did not find any resistance to vancomycin (median MIC 0.5 μg/mL), metronidazole (median MIC 1 μg/mL), and tigecycline (median MIC 0.016 μg/mL), while resistance to ciprofloxacin was detected in all the samples. Among the recurrent isolates, 37.5% displayed a 2-fold MIC increase for vancomycin, 75% for metronidazole, and 37.5% for tigecycline. After stratifying clinical outcomes according to vancomycin MIC, patients with higher MIC experienced increased 28-day mortality (p value 0.009). Our results were concordant with European surveillance data. MIC increase in all tested antibiotics in patients with CDI warrants further research since decreased susceptibility has been associated with clinical failure.