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Genomic Epidemiology of Multidrug-Resistant Organisms from Humans and Food Animals.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Genomic Epidemiology of Multidrug-Resistant Organisms from Humans and Food Animals./
作者:	Zhu, Chendi.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	156 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-06, Section: B.
Contained By:	Dissertations Abstracts International83-06B.
標題:	Microbiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28940811
ISBN:	9798496515283

Genomic Epidemiology of Multidrug-Resistant Organisms from Humans and Food Animals.
Zhu, Chendi.

Genomic Epidemiology of Multidrug-Resistant Organisms from Humans and Food Animals. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 156 p.

Source: Dissertations Abstracts International, Volume: 83-06, Section: B.

Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 2021.

This item is not available from ProQuest Dissertations & Theses.

The emergence of carbapenemase-producing Enterobacteriaceae (CPE) has thwarted clinical treatment of infections caused by multidrug-resistant Gram-negative bacteria. The spread of CPE in hospitals, communities and food animals poses great challenges to public health. Comprehensive analysis with molecular typing is vital to understand the epidemiological trends and transmission patterns of antimicrobial resistance to guide infection control and prevention policies. The application of whole genome sequencing (WGS) has vastly improved the ability to elucidate the antimicrobial resistance genes involved, their transmission patterns and phylogenetic relationship among CPE isolated in various populations. The objectives of this study were (1) to describe the changing pattern and characterize CPE isolates in Hong Kong hospitals using WGS; (2) to characterize acquired virulence factors and antimicrobial resistance genes in carbapenemase-producing Klebsiella pneumoniae in a Sri Lankan hospital; (3) to screen and characterize multidrug-resistant organisms (MDROs) colonized in healthy subjects in Hong Kong; and (4) comparative genomic analysis of NDMproducing E. coli (NDM-E) from different sources (hospitalized patients, healthy subjects in community and food animals). The molecular epidemiology of 567 CPE isolates from patients of three of the seven public hospital clusters in Hong Kong in a seven-year period (2011-2017) was elucidated. The incidence of CPE isolation increased from 0.05 to 9.6 /100,000 inpatient-days. The most prevalent carbapenemase genes were blaNDM (55.1%), blaIMP (30.0%), blaKPC (8.7%), blaOXA- 48-like (6.9%), and blaIMI (1.9%). E. coli (46.4%) and Klebsiella spp. (38.3%) were the dominant species. WGS was performed on 169 representative isolates. Two distinct lineages of blaKPC-2- positive Klebsiella pneumoniae (ST11 & ST258) were identified with ST11 carrying yersiniabactin gene ybt-9 on ICEKp3. ST131 E. coli producing IMP-4 was a locally transmitted clone throughout the study period. The blaNDM and blaIMP genes were mainly carried in IncX3 and IncN-ST7 plasmids respectively. BlaOXA-48-like gene was carried in IncX3 plasmid in E. coli but ColKP3 plasmid in K. pneumoniae. A lineage of K. pneumoniae with blaNDM-1 plus blaOXA- 232/OXA-181 in a distinct blaNDM-embedding plasmid (IncF1B/IncHI1B) was identified and associated with patients who had prior overseas hospitalization. The prevalence of CPE in the intensive care units of a teaching hospital in Sri Lanka was studied. In a six-month period of 2015, CPE was identified in 2.6% of 379 respiratory specimens. All ten strains were Klebsiella pneumoniae-producing blaOXA-181, in which two strains of ST437 and eight isolates were ST147. Carbapenemase genes were located on three variants of ColE-type plasmids, with the longest being 7,606 bp. Genes encoding for extended spectrum β-lactamases (ESBL) (blaCTX-M-15, blaSHV-11), plasmid-mediated quinolone resistance (PMQR) determinants (qnr, aac(6')-Ib-cr and oqxAB) were present in all strains. Amino acid substitution in chromosomal quinolone resistance-determining regions (QRDRs) gyrA (Ser83Ile) and parC (Ser80Ile) were also observed. All strains had yersiniabactin genes on mobile element ICEkp. A prevalence study on the carriage of MDROs of healthy subjects in Hong Kong was performed. The study involved longitudinal screening on the colonization of methicillin-resistant Staphylococcus aureus (MRSA), ESBL producing Enterobacteriaceae (ESBL-E) and CPE from 1076 healthy subjects over a 3-year period (2017-2019). The prevalence of MRSA was 1.2%-2.5% among the 3 years with six carriers persistently positive after one year of screening. Among 31 MRSA isolates, ST22/SCCmecIV(2B), also known as EMRSA-15 was the major lineage (29%). MRSA from the same prolonged carriers were closely related. Only one MRSA strain carried Panton-Valentine Leucocidin (PVL) genes (lukF & lukS) while another leukocidin gene, lukED, was found in 41.9% strains. ESBL-E was detected in 43.4%- 54.8% subjects during the 3-year period. PCR of blaCTX-M genes revealed blaCTX-M-G9 was the most prevalent type in the 1st year and 2nd year studies while blaCTX-M-G1 dominated in the 3rd year study. CPE carriage rate ranged from 0.5% to 2% and was predominated by blaNDMpositive E. coli with the gene located in IncX3 plasmid. CPE with other carbapenemase types (OXA-181, IMI-6) were also found in healthy people. A comparative genomic analysis of 83 strains of NDM-producing E. coli (NDM-E) isolated from community dwellers, clinical patients and food animal products (pig organs from wet markets) in Hong Kong were analyzed. In addition, whole genomes of 961 NDM-E from across the globe were included in the analysis to compare the phylogeny and molecular characteristics of Hong Kong strains against the global strains of different sources and regions. IncX3 plasmid carrying blaNDM-5 prevailed in NDM-E from diverse sources in Hong Kong, but distinct clones and AMR genes were observed in NDM-E from human and food animals. The presence of phenicol-resistant genes (floR, cmlA) was significantly higher in swine-source isolates while fewer ESBL genes were observed. Mobile genetic elements (MGEs) carrying blaNDM varied across regions while blaNDM-positive IncX3 plasmid is a global menace. IncB/O/K/Z plasmids were exclusively found in Chinese farms and clinical patients. IncA/C2 plasmids were frequently carried by European strains but were not found in China. We also found that ST48 lineage was restricted to China and comprised of NDM-E from different sources in Hong Kong as well as poultry, feed and sewage in Chinese farms. In conclusion, comprehensive molecular epidemiology of CPE was described in Hong Kong. WGS-based in-depth analysis was conducted to reveal the phylogenetic relationship, MGEs, and accessory gene profiles. We established the emergence of EMRSA-15 and a high percentage of ESBL-E carriage within the healthy population of Hong Kong, while CPE was also detectable. NDM-producing Enterobacteriaceae was the most prevalent CPE from different sources. IncX3 plasmid-mediated transmission of NDM-producing Enterobacteriaceae was the major source of CPE in Hong Kong and worldwide.

ISBN: 9798496515283Subjects--Topical Terms:

536250
Microbiology.
Subjects--Index Terms:

Carbapenemase-producing Enterobacteriaceae

Genomic Epidemiology of Multidrug-Resistant Organisms from Humans and Food Animals.
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520 $a The emergence of carbapenemase-producing Enterobacteriaceae (CPE) has thwarted clinical treatment of infections caused by multidrug-resistant Gram-negative bacteria. The spread of CPE in hospitals, communities and food animals poses great challenges to public health. Comprehensive analysis with molecular typing is vital to understand the epidemiological trends and transmission patterns of antimicrobial resistance to guide infection control and prevention policies. The application of whole genome sequencing (WGS) has vastly improved the ability to elucidate the antimicrobial resistance genes involved, their transmission patterns and phylogenetic relationship among CPE isolated in various populations. The objectives of this study were (1) to describe the changing pattern and characterize CPE isolates in Hong Kong hospitals using WGS; (2) to characterize acquired virulence factors and antimicrobial resistance genes in carbapenemase-producing Klebsiella pneumoniae in a Sri Lankan hospital; (3) to screen and characterize multidrug-resistant organisms (MDROs) colonized in healthy subjects in Hong Kong; and (4) comparative genomic analysis of NDMproducing E. coli (NDM-E) from different sources (hospitalized patients, healthy subjects in community and food animals). The molecular epidemiology of 567 CPE isolates from patients of three of the seven public hospital clusters in Hong Kong in a seven-year period (2011-2017) was elucidated. The incidence of CPE isolation increased from 0.05 to 9.6 /100,000 inpatient-days. The most prevalent carbapenemase genes were blaNDM (55.1%), blaIMP (30.0%), blaKPC (8.7%), blaOXA- 48-like (6.9%), and blaIMI (1.9%). E. coli (46.4%) and Klebsiella spp. (38.3%) were the dominant species. WGS was performed on 169 representative isolates. Two distinct lineages of blaKPC-2- positive Klebsiella pneumoniae (ST11 & ST258) were identified with ST11 carrying yersiniabactin gene ybt-9 on ICEKp3. ST131 E. coli producing IMP-4 was a locally transmitted clone throughout the study period. The blaNDM and blaIMP genes were mainly carried in IncX3 and IncN-ST7 plasmids respectively. BlaOXA-48-like gene was carried in IncX3 plasmid in E. coli but ColKP3 plasmid in K. pneumoniae. A lineage of K. pneumoniae with blaNDM-1 plus blaOXA- 232/OXA-181 in a distinct blaNDM-embedding plasmid (IncF1B/IncHI1B) was identified and associated with patients who had prior overseas hospitalization. The prevalence of CPE in the intensive care units of a teaching hospital in Sri Lanka was studied. In a six-month period of 2015, CPE was identified in 2.6% of 379 respiratory specimens. All ten strains were Klebsiella pneumoniae-producing blaOXA-181, in which two strains of ST437 and eight isolates were ST147. Carbapenemase genes were located on three variants of ColE-type plasmids, with the longest being 7,606 bp. Genes encoding for extended spectrum β-lactamases (ESBL) (blaCTX-M-15, blaSHV-11), plasmid-mediated quinolone resistance (PMQR) determinants (qnr, aac(6')-Ib-cr and oqxAB) were present in all strains. Amino acid substitution in chromosomal quinolone resistance-determining regions (QRDRs) gyrA (Ser83Ile) and parC (Ser80Ile) were also observed. All strains had yersiniabactin genes on mobile element ICEkp. A prevalence study on the carriage of MDROs of healthy subjects in Hong Kong was performed. The study involved longitudinal screening on the colonization of methicillin-resistant Staphylococcus aureus (MRSA), ESBL producing Enterobacteriaceae (ESBL-E) and CPE from 1076 healthy subjects over a 3-year period (2017-2019). The prevalence of MRSA was 1.2%-2.5% among the 3 years with six carriers persistently positive after one year of screening. Among 31 MRSA isolates, ST22/SCCmecIV(2B), also known as EMRSA-15 was the major lineage (29%). MRSA from the same prolonged carriers were closely related. Only one MRSA strain carried Panton-Valentine Leucocidin (PVL) genes (lukF & lukS) while another leukocidin gene, lukED, was found in 41.9% strains. ESBL-E was detected in 43.4%- 54.8% subjects during the 3-year period. PCR of blaCTX-M genes revealed blaCTX-M-G9 was the most prevalent type in the 1st year and 2nd year studies while blaCTX-M-G1 dominated in the 3rd year study. CPE carriage rate ranged from 0.5% to 2% and was predominated by blaNDMpositive E. coli with the gene located in IncX3 plasmid. CPE with other carbapenemase types (OXA-181, IMI-6) were also found in healthy people. A comparative genomic analysis of 83 strains of NDM-producing E. coli (NDM-E) isolated from community dwellers, clinical patients and food animal products (pig organs from wet markets) in Hong Kong were analyzed. In addition, whole genomes of 961 NDM-E from across the globe were included in the analysis to compare the phylogeny and molecular characteristics of Hong Kong strains against the global strains of different sources and regions. IncX3 plasmid carrying blaNDM-5 prevailed in NDM-E from diverse sources in Hong Kong, but distinct clones and AMR genes were observed in NDM-E from human and food animals. The presence of phenicol-resistant genes (floR, cmlA) was significantly higher in swine-source isolates while fewer ESBL genes were observed. Mobile genetic elements (MGEs) carrying blaNDM varied across regions while blaNDM-positive IncX3 plasmid is a global menace. IncB/O/K/Z plasmids were exclusively found in Chinese farms and clinical patients. IncA/C2 plasmids were frequently carried by European strains but were not found in China. We also found that ST48 lineage was restricted to China and comprised of NDM-E from different sources in Hong Kong as well as poultry, feed and sewage in Chinese farms. In conclusion, comprehensive molecular epidemiology of CPE was described in Hong Kong. WGS-based in-depth analysis was conducted to reveal the phylogenetic relationship, MGEs, and accessory gene profiles. We established the emergence of EMRSA-15 and a high percentage of ESBL-E carriage within the healthy population of Hong Kong, while CPE was also detectable. NDM-producing Enterobacteriaceae was the most prevalent CPE from different sources. IncX3 plasmid-mediated transmission of NDM-producing Enterobacteriaceae was the major source of CPE in Hong Kong and worldwide.
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