Molecular Epidemiology and Antimicrobial Resistance of Clostridioides difficile in Hospitalized Patients From Mexico

Abstract

<i>Clostridioides difficile</i> is a global public health problem, which is a primary cause of antibiotic-associated diarrhea in humans. The emergence of hypervirulent and antibiotic-resistant strains is associated with the increased incidence and severity of the disease. There are limited studies on genomic characterization of <i>C. difficile</i> in Latin America. We aimed to learn about the molecular epidemiology and antimicrobial resistance in <i>C. difficile</i> strains from adults and children in hospitals of México. We studied 94 <i>C. difficile</i> isolates from seven hospitals in Mexico City from 2014 to 2018. Whole-genome sequencing (WGS) was used to determine the genotype and examine the toxigenic profiles. Susceptibility to antibiotics was determined by <i>E</i>-test. Multilocus sequence typing (MLST) was used to determine allelic profiles. Results identified 20 different sequence types (ST) in the 94 isolates, mostly clade 2 and clade 1. ST1 was predominant in isolates from adult and children. Toxigenic strains comprised 87.2% of the isolates that were combinations of <i>tcdAB</i> and <i>cdtAB</i> (<i>tcdA+/tcdB+/cdtA+/cdtB+</i>, followed by <i>tcdA+/tcdB+/cdtA-/cdtB-</i>, <i>tcdA</i>-/<i>tcdB+/cdtA-/ cdtB-</i>, and <i>tcdA-</i>/<i>tcdB-/cdtA+/cdtB+</i>). Toxin profiles were more diverse in isolates from children. All 94 isolates were susceptible to metronidazole and vancomycin, whereas a considerable number of isolates were resistant to clindamycin, fluroquinolones, rifampicin, meropenem, and linezolid. Multidrug-resistant isolates (≥3 antibiotics) comprised 65% of the isolates. The correlation between resistant genotypes and phenotypes was evaluated by the kappa test. Mutations in <i>rpoB</i> and <i>rpoC</i> showed moderate concordance with resistance to rifampicin and mutations in <i>fusA</i> substantial concordance with fusidic acid resistance. <i>cfrE</i>, a gene recently described in one Mexican isolate, was present in 65% of strains linezolid resistant, all ST1 organisms. WGS is a powerful tool to genotype and characterize virulence and antibiotic susceptibility patterns.