High Prevalence of Genetically Related Clostridium Difficile Strains at a Single Hemato-Oncology Ward Over 10 Years.

Edyta Waker,Filip Ambrozkiewicz,Michał Mikula,Łukasz Targoński,Patrycja Cybula,Jan Walewski,Jerzy Ostrowski,Karolina Skubisz,Agnieszka Paziewska,Maria Kulecka

doi:10.3389/fmicb.2020.01618

Abstract

Aims: Clostridium difficile (C. difficile) infection (CDI) is the main cause of healthcare-associated infectious diarrhea. We used whole-genome sequencing (WGS) to measure the prevalence and genetic variability of C. difficile at a single hemato-oncology ward over a 10 year period.Methods: Between 2008 and 2018, 2077 stool samples were obtained from diarrheal patients hospitalized at the Department of Lymphoma; of these, 618 were positive for toxin A/B. 140 isolates were then subjected to WGS on Ion Torrent PGM sequencer.Results: 36 and 104 isolates were recovered from 36 to 46 patients with single and multiple CDIs, respectively. Of these, 131 strains were toxigenic. Toxin gene profiles tcdA(+);tcdB(+);cdtA/cdtB(+) and tcdA(+);tcdB(+);cdtA/cdtB(-) were identified in 122 and nine strains, respectively. No isolates showed reduced susceptibility to metronidazole and vancomycin. All tested strains were resistant to ciprofloxacin, and 72.9, 42.9, and 72.9% of strains were resistant to erythromycin, clindamycin, or moxifloxacin, respectively. Multi-locus sequence typing (MLST) identified 23 distinct sequence types (STs) and two unidentified strains. Strains ST1 and ST42 represented 31 and 30.1% of all strains tested, respectively. However, while ST1 was detected across nearly all years studied, ST42 was detected only from 2009 to 2011.Conclusion: The high proportion of infected patients in 2008–2011 may be explained by the predominance of more transmissible and virulent C. difficile strains. Although this retrospective study was not designed to define outbreaks of C. difficile, the finding that most isolates exhibited high levels of genetic relatedness suggests nosocomial acquisition.

Highlights

Clostridioides (Clostridium) difficile (C. difficile) is an anaerobic, Gram-positive, spore-forming, and toxin-producing bacillus identified as the main cause of healthcare-associated infectious diarrhea (Carroll and Bartlett, 2011; Rodríguez Garzotto et al, 2015; Czepiel et al, 2019)
MLST Results We used unique combinations of alleles selected from housekeeping gene sequences, referred to as multi-locus sequence typing (MLST), which can assign C. difficile strains to any one of six distinct phylogenetic clades (Janezic and Rupnik, 2015)
Of the 82 strains recovered from patients with a single C. difficile infection (CDI), or from patients with multiple CDIs during the first episode, 23 (28%) and 23 (28%) were ST1 and ST42, respectively

Summary

Introduction

Clostridioides (Clostridium) difficile (C. difficile) is an anaerobic, Gram-positive, spore-forming, and toxin-producing bacillus identified as the main cause of healthcare-associated infectious diarrhea (Carroll and Bartlett, 2011; Rodríguez Garzotto et al, 2015; Czepiel et al, 2019). Non-infective etiologies include mucosal injury caused by cytotoxic chemotherapy or radiation, infectious diarrhea relates mostly to CDI arising from neutropenia requiring treatment with antibiotics (Carroll and Bartlett, 2011; Alonso et al, 2012; Alasmari et al, 2014). Rates of CDI in cancer patients subjected to prolonged antibiotic treatment, chemotherapy, and/or radiotherapy; rates in those subjected to frequent or prolonged hospitalization; and rates in those with a depressed immune response (Louie et al, 2013; Park et al, 2016; Shin et al, 2016; Smits et al, 2016; Cornely et al, 2018; Shoaei et al, 2019) are approximately two times higher than those of the general hospital population (Kamboj et al, 2012). Evaluation of CDI risk is often challenging because the incidence of CDI among hospitalized cancer patients differs nationwide (Costa et al, 2017)

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Results

Conclusion