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Molecular Epidemiology and Antimicrobial Resistance of Clostridioides difficile in Hospitalized Patients From Mexico
Emmanuel Aguilar-Zamora1,2, Bart C Weimer3, Roberto C Torres1
1Unidad de Investigación Medica en Enfermedades Infecciosas y Parasitarias, UMAE Pediatría, CMN Siglo XXI, IMSS, México City, Mexico.
Abstract:
Clostridioides difficile 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 C. difficile in Latin America. We aimed to learn about the molecular epidemiology and antimicrobial resistance in C. difficile strains from adults and children in hospitals of México. We studied 94 C. difficile 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 E-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 tcdAB and cdtAB (tcdA+/tcdB+/cdtA+/cdtB+, followed by tcdA+/tcdB+/cdtA-/cdtB-, tcdA-/tcdB+/cdtA-/ cdtB-, and tcdA-/tcdB-/cdtA+/cdtB+). 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 rpoB and rpoC showed moderate concordance with resistance to rifampicin and mutations in fusA substantial concordance with fusidic acid resistance. cfrE, 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.
Insights
Clostridioides difficile infections are a growing concern, with hypervirulent strains emerging. This study characterized C. difficile strains from Mexico, finding high rates of multidrug resistance, particularly in ST1 strains, highlighting the need for genomic surveillance.
Area of Science:
- Genomics and Molecular Epidemiology
- Antimicrobial Resistance
- Infectious Diseases
Background:
- Clostridioides difficile is a significant cause of antibiotic-associated diarrhea globally.
- Hypervirulent and antibiotic-resistant strains are increasing disease incidence and severity.
- Limited genomic data exists for C. difficile in Latin America.
Purpose of the Study:
- To investigate the molecular epidemiology of C. difficile in Mexican hospitals.
- To characterize antimicrobial resistance patterns and toxigenic profiles of C. difficile isolates.
Main Methods:
- Whole-genome sequencing (WGS) was employed for genotyping and toxigenic profiling.
- Antibiotic susceptibility testing was performed using E-test.
- Multilocus sequence typing (MLST) determined allelic profiles.
Main Results:
- Twenty sequence types (STs) were identified, with ST1 being predominant in both adult and pediatric isolates.
- 87.2% of isolates were toxigenic, exhibiting diverse toxin profiles, with greater diversity in pediatric strains.
- All isolates were susceptible to metronidazole and vancomycin, but significant resistance was observed for clindamycin, fluoroquinolones, rifampicin, meropenem, and linezolid. 65% of isolates were multidrug-resistant (MDR).
Conclusions:
- Genomic characterization revealed a predominance of ST1 C. difficile in Mexico.
- High rates of MDR highlight treatment challenges; specific resistance mechanisms like cfrE in ST1 strains warrant further investigation.
- WGS is a valuable tool for understanding C. difficile epidemiology, virulence, and antimicrobial resistance.
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