Abstract
Background
Antimicrobial susceptibility testing (AST) is not routinely performed for
Clostridioides difficile and data evaluating minimum inhibitory concentrations (MICs) are limited. We performed AST and whole genome sequencing (WGS) for 593
C. difficile isolates collected between 2012-2017 through the Centers for Disease Control and Prevention's Emerging Infections Program.
M ethods
MICs to six antimicrobial agents (ceftriaxone, clindamycin, meropenem, metronidazole, moxifloxacin, and vancomycin) were determined using the reference agar dilution method according to Clinical and Laboratory Standards Institute guidelines. WGS was performed on all isolates to detect the presence of genes or mutations previously associated with resistance.
Results
Among all isolates, 98.5% displayed a vancomycin MIC ≤ 2 μg/mL and 97.3% displayed a metronidazole MIC ≤ 2 μg/mL. Ribotype 027 (RT027) isolates displayed higher vancomycin MICs (MIC
50: 2 μg/mL; MIC
90: 2 μg/mL) than non-RT027 isolates (MIC
50: 0.5 μg/mL; MIC
90: 1 μg/mL) (P < 0.01). No
vanA/B genes were detected. RT027 isolates also showed higher MICs to clindamycin and moxifloxacin and were more likely to harbor associated resistance genes or mutations.
Conclusions
Elevated MICs to antib iotics used for treatment of
C. difficile infection were rare and there was no increase in MICs over time. The lack of
vanA/B genes or mutations consistently associated with elevated vancomycin MICs suggests there are multifactorial mechanisms of resistance. Ongoing surveillance of
C. difficile using reference AST and WGS to monitor MIC trends and the presence of antibiotic resistance mechanisms is essential.