Molecular epidemiology, antimicrobial susceptibility, and toxin production of clinical Clostridioides difficile isolates from a teaching hospital in Northern China

Clostridioides difficile (C. diff) is an anaerobic, spore-forming, and gram-positive pathogen that is a significant cause of healthcare-associated infections around the world. In addition to abdominal pain, diarrhea, and fever, patients with Clostridioides difficile infection (CDI) may also develop serious complications such as pseudomembranous enterocolitis, toxic megacolon, and even death due to sepsis if the treatment provided is not prompt and accurate [1]. The pathogenicity of C. diff is mainly attributable to toxin A and B, which are encoded on the 19.6-kb pathogenicity locus by tcdA and tcdB, respectively, and negatively regulated by the expression of accessory genes tcdC. Besides, the binary toxin (CDT), a third toxin that is encoded by cdtA/B genes in a chromosomal 6.2-kb region known as CDT locus, is also detected in strains of specific sequence types (STs) [2].

In the past, the awareness of CDI prevention and control was weak in China owing to the limited capacity of laboratory diagnosis [3]. However, in the last decades, the outbreak and spread of hypervirulent and multidrug-resistant strain BI/NAP1/027 in Europe and North America makes people realize that a thorough survey of molecular epidemiological and systematic analysis of antimicrobial susceptibility are two indispensable parts of effective works on CDI prevention and treatment [4].

Multilocus sequence typing (MLST) is a general tool that is used to analyze genetic and phylogenetic features of C. diff according to allelic polymorphisms in seven housekeeping genes. It is reported that ST81, a strain with the toxin genotype of tcdA-negative, tcdB-positive, and cdtA/B-negative (A-B+CDT-) from MLST clade IV, has become the most prevalent ST causing hospital and community acquired CDI in mainland China [5,6]. Nowadays, metronidazole and vancomycin are still the top 2 candidates for CDI treatment in China [7]. However, C. diff strains with hetero-resistance to metronidazole have emerged in domestic areas [8,9]. Several population-based surveillance studies from abroad have revealed that the minimum inhibitory concentrations (MICs) values of vancomycin against C. diff showed a significant upward trend [10,11]. Given the irregular changes of the molecular types and antibiotic MIC within a short time and same region, the prevention and control measures against CDI by consistent monitoring are worth encouraging and promoting.

In this study, we conduct a comprehensive investigation of the molecular genotypes, antimicrobial resistance patterns, and the toxin-producing abilities of clinical C. diff isolates collected from a tertiary teaching hospital in Beijing, China, to provide a solid foundation for the in-depth mechanisms of drug resistance in C. diff treatment and make beneficial attempts to seek a reference point for further epidemiological and genomic surveillance of CDI.

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