Influence of Binary Toxin Gene Detection and Decreased Susceptibility to Antibiotics among Clostridioides difficile Strains on Disease Severity: a Single-Center Study

Clostridioides difficile infection (CDI) is the fifth leading cause of death from nonmalignant gastrointestinal disease in the United States. The contribution of resistance to C. difficile-active antibiotics to the outcomes of CDI is unclear. We evaluated the antimicrobial susceptibility of C. difficile isolates in a U.S. hospital and determined associations of clinical variables and binary toxin positivity with antibiotic resistance. C. difficile spores were cultured from fecal specimens of adult patients with CDI for genotyping and antimicrobial susceptibility assay (for clindamycin [CLI], fidaxomicin [FDX], metronidazole [MTZ], moxifloxacin [MXF], tigecycline [TGC], and vancomycin [VAN]). Electronic medical records were reviewed for clinical data extraction. Ninety-seven of 130 (75%) fecal samples grew toxigenic C. difficile in culture. Most of the isolates were tcdA(+) tcdB(+) cdtB(-) (80.4%), and 18.6% and 1% were tcdA(+) tcdB(+) cdtB(+) and tcdA(-) tcdB(+) cdtB(+), respectively. Susceptibility to VAN, MTZ, FDX, TGC, MXF, and CLI was 96%, 94%, 100%, 100%, 8%, and 79%, respectively. Six isolates, all cdtB positive and belonging to the 027 ribotype, were resistant to VAN and/or MTZ. Higher MICs were found in isolates with a mutation in the VAN-related resistance gene vanR, but not vans. In addition, cdtB(+) isolates exhibited higher MICs of VAN, MTZ, TGC, CLI, and MXF compared to cdtB(-) strains. Patients with greater intestinal inflammation or severe disease were more likely to be infected with cdtB(+) strains. Decreased susceptibility to antibiotics is not directly associated with either severe or recurrent CDI. However, antimicrobial susceptibility of C. difficile is decreased in strains positive for the binary toxin gene.