Genomic Surveillance of Carbapenem-Resistant Klebsiella pneumoniae from a Major Public Health Hospital in Singapore

Teo, Jin Yao; Tang, Cheng Yee; Tan, Si Hui; Chang, Hong Yi; Ong, Sze Min; Lee, Shannon Jing-Yi; Koh, Tse-Hsien; Sim, James Heng-Chiak; Kwa, Andrea Lay-Hoon; Ong, Rick Twee‐Hee

doi:10.1128/spectrum.00957-22

Cited by 11 publications

(12 citation statements)

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“…The Infectious Diseases Society of America has issued a guidance on the treatment of CRE isolates, recommending BLBLIs as the preferred antibiotics for the treatment of most types of infections since carbapenemase-negative or KPC-producing pathogens prevailed in that region ( 15 ). Owing to the relatively high local MBL prevalence, these geographic-specific guidelines are not relevant in Singapore ( 16 , 17 ). However, our study found that ceftazidime-avibactam inhibited 80 to 90% of non-MBL-producing isolates.…”

Section: Discussionmentioning

confidence: 99%

Comparative Activities of Novel Therapeutic Agents against Molecularly Characterized Clinical Carbapenem-Resistant Enterobacterales Isolates

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Comparative Activities of Novel Therapeutic Agents against Molecularly Characterized Clinical Carbapenem-Resistant Enterobacterales Isolates

et al. 2023

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“…One clade that carries ybt16 is limited to the north, whereas the clade with the ybt9 gene shows a nationwide distribution across six regions and twelve hospitals (Figure 7). The clade with the ybt16 gene also had GyrA-83Y and GyrA-87A mutations, while the clade with ybt9 had GyrA-83I mutations (Supplemental Table S1), showing the divergent evolutionary history of ciprofloxacin resistance in the two clades, driven by ciprofloxacin treatment [6]. The lineages in both clades carried virulence genes, i.e., the iuc locus and rmp on the Q97_2 plasmid, as well as multiple plasmid-borne carbapenemase genes, bla OXA-48 , bla OXA-181 , bla NDM-1 , bla NDM-5 and bla KPC-2, independently (Figure 7).…”

Section: Resultsmentioning

confidence: 99%

“…The evolution of multidrug-resistant K. pneumoniae is characterized by the expansion of clones at the hospital level driven by nosocomial transmission routes, followed by regional and global expansion due to strong selective pressure from antimicrobial agents. The local epidemiological and clinical characteristics of K. pneumoniae have been reported in multicentre studies in different countries [6, 33, 40–42], revealing expansions of both endemic clones and imported clones, with clonal expansion mostly caused by the globally known ST258 lineage. Our results concur with the findings of these studies, showing similar clonal expansion of globally and regionally circulating clones in the KSA.…”

Section: Discussionmentioning

confidence: 99%

“…These strains are commonly recovered from various distant geographical locations, can colonize, or infect multiple hosts and are rapidly transmitted across hosts and settings. The best-characterized international clones are CG258, which include ST258, S11, clonal groups CG14/15, CG17/20, CG43, CG147, and ST101 [4][5][6]. In recent decades, these clades have converged between carbapenem resistance and virulence [7].…”

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The Dissemination of Multidrug-Resistant and HypervirulentKlebsiella pneumoniaeClones Across the Kingdom of Saudi Arabia

Huang,

Alhejaili,

Alkherd

et al. 2024

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The Gram-negative bacterium Klebsiella pneumoniae is a major human health threat underlying a broad range of community- and hospital-associated infections. The emergence of clonal hypervirulent strains often resistant to last-resort antimicrobial agents has become a global burden as treatment options are limited. The Kingdom of Saudi Arabia (KSA) has a dynamic and diverse population and serves as a major global tourist hub facilitating the dissemination of multidrug-resistant (MDR) strains of K. pneumoniae. To examine the spread of clinically relevant Klebsiella pneumoniae strains, we characterized the population structure and dynamics of multidrug-resistant K. pneumoniae across the KSA hospitals. Methods We conducted a large genomic survey on a Saudi Arabian collection of multidrug-resistant K. pneumoniae isolates from bloodstream and urinary tract infections. The isolates were collected from 32 hospitals located in 15 major cities across the country in 2022 and 2023. We subjected 352 K. pneumoniae isolates to whole-genome sequencing and employed a broad range of genomic epidemiological and phylodynamic methods to analyse population structure and dynamics at high resolution. We employed an integrated short- and long-read sequencing approach to fully characterize multiple plasmids carrying resistance and virulence genes. Results Our results indicate that, despite a diverse K. pneumoniae population underlying hospital infections, the population is characterized by the rapid expansion of a few dominant clones, including ST096 (n=115), ST147 (n=75), ST231 (n=35), ST101 (n=30), ST11 (n=18), ST16 (n=15) and ST14 (n=12). ST2096, ST231, and ST147 clones were estimated to have formed within the past two decades and spread between hospitals across the country on an epidemiological time scale. All STs were genetically linked with globally circulating clones, particularly strains from the Middle East and South Asia. All of the major clones harboured plasmid-borne ESBLs and a range of carbapenemase genes. Plasmidome analysis revealed multiple mosaic plasmids with resistance and virulence gene cassettes, some of which were shared between the major clades and account for multidrug resistant hypervirulent (MDR/hv) phenotype, especially in the ST2096 strains. Integration of phylodynamic data and resistance plasmid profiles showed that the acquisition of plasmids occurred on the same time scales as did the expansion of major clones across the country. Conclusion Taken together, these results indicate the dissemination of MDR and MDR-hv K. pneumoniae strains across the kingdom and provide evidence for pervasive plasmid sharing and horizontal gene transfer of resistance genes. The results demonstrate the independent introduction of endemic ST147, ST231, and ST101 clones into the country and highlight the clinical significance of ST2096 as an emerging clone with dual resistance and virulence risks. These results highlight the need for continuous surveillance of circulating and newly emergent strains (STs) and of their plasmidome footprints carrying MDR determinants.

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“…Genome data found that both the K. pneumoniae isolates have different STs and showed no clonal relationship with the global tet(X4)-positive K. pneumoniae strains in the NCBI database indicative of genetic diversity. Additionally, single tet(X4)-positive E. coli isolate belonged to ST746 which have been previously associated with carbapenem resistance in Korea 32 and China 33 . It has been suggested that mobile genetic element not the clones play an important role in tet(X4) transmission 27 .…”

Section: Discussionmentioning

confidence: 96%

Emergence and genomic characterization of Klebsiella pneumoniae and Escherichia coli harboring tet(X4) disseminated by Black kites (Milvus migrans)

Mansoor,

Lu,

Voksepp

et al. 2023

Preprint

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The emergence of plasmid-mediated tigecycline resistance gene tet(X4) among clinically relevant bacteria has raised serious concerns since tigecycline is considered as last-resort drug against serious infections caused by multidrug-resistant bacteria. We herein focused on the isolation and molecular characterization of tet(X4)-positive Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) in wild bird populations with anthropogenic interaction in Faisalabad, Pakistan. A total of 150 birds including black kites (Milvus migrans) and house crows (Corvus splendens) were screened for the presence of tigecycline resistance K. pneumoniaeand E. coli. We found two K. pneumoniae and one E. coliisolate carrying tet(X4) originated from black kites. A combination of short- and long-read sequencing strategy showed that tet(X4) was located on a broad host range IncFII plasmid family inK. pneumoniae isolates whereas on an IncFII-IncFIB hybrid plasmid in E. coli. We also found an integrative and conjugative element ICEKp2 in K. pneumoniae isolate KP8336. The combination of tet(X4) and a known virulence associated ICEKp2 in a wild bird with significant human interaction is particularly worrisome. We demonstrated the first description of tet(X4) gene in the WHO critical-priority pathogen K. pneumoniae among wild birds with known anthropogenic interaction and dispersal potential. The potential risk of global transmission of tet(X4)-positive K. pneumoniae and E. coli warrant comprehensive evaluation.

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Genomic Surveillance of Carbapenem-Resistant Klebsiella pneumoniae from a Major Public Health Hospital in Singapore

Cited by 11 publications

References 61 publications

Comparative Activities of Novel Therapeutic Agents against Molecularly Characterized Clinical Carbapenem-Resistant Enterobacterales Isolates

Comparative Activities of Novel Therapeutic Agents against Molecularly Characterized Clinical Carbapenem-Resistant Enterobacterales Isolates

The Dissemination of Multidrug-Resistant and HypervirulentKlebsiella pneumoniaeClones Across the Kingdom of Saudi Arabia

Emergence and genomic characterization of Klebsiella pneumoniae and Escherichia coli harboring tet(X4) disseminated by Black kites (Milvus migrans)

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