The spread of KPC-producing Enterobacteriaceae in Spain: WGS analysis of the emerging high-risk clones ofKlebsiella pneumoniaeST11/KPC-2, ST101/KPC-2 and ST512/KPC-3

Oteo, Jesús; Pérez-Vázquez, Marı́a; Bautista, Verónica; Ortega, Adriana; Zamarrón, Pilar; Sáez, David; Fernández-Romero, Sara; Lara, Noelia; Ramiro, Raquel; Aracil, Belén; Campos, José

doi:10.1093/jac/dkw321

Cited by 66 publications

(50 citation statements)

References 58 publications

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“…S6) and was the same as that previously detected in the first IncP6 plasmid carrying bla KPC-2 in K. oxytoca (6). The other one was an IncFIB plasmid of ϳ103 kb that was similar to the plasmid with GenBank accession number NZ_CP015395.1 (average identity, Ͼ95%; average coverage percentage, 88.36%) and that harbored bla KPC-3 in the classical transposon Tn4401 isoform (27,28), bla TEM-1A , and bla OXA-9 (Fig. S7).…”

Section: Resultssupporting

confidence: 53%

Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016–2017

Pérez-Vázquez

Oteo

Sola‐Campoy

et al. 2019

Antimicrob Agents Chemother

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There is little information about carbapenemase-producing (CP) Klebsiella oxytoca, an important nosocomial pathogen. We characterized CP K. oxytoca isolates collected from different Spanish hospitals between January 2016 and October 2017. During the study period, 139 nonduplicate CP K. oxytoca isolates were identified; of these, 80 were studied in detail. Carbapenemase and extendedspectrum ␤-lactamase genes were identified by PCR and sequencing. Genetic relatedness was studied by pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing (WGS), carried out on 12 representative isolates, was used to identify the resistome, to elucidate the phylogeny, and to determine the plasmids harboring carbapenemase genes. Forty-eight (60%) isolates produced VIM-1, 30 (37.5%) produced OXA-48, 3 (3.7%) produced KPC-2, 2 (2.5%) produced KPC-3, and 1 (1.2%) produced NDM-1; 4 isolates coproduced two carbapenemases. By PFGE, 69 patterns were obtained from the 80 CP K. oxytoca isolates, and four well-defined clusters were detected: cluster 1 consisted of 11 OXA-48-producing isolates, and the other three clusters included VIM-1-producing isolates (5, 3, and 3 isolates, respectively). In the 12 sequenced isolates, the average number of acquired resistance genes was significantly higher in VIM-1-producing isolates (10.8) than in OXA-48-producing isolates (2.3). All 12 isolates had chromosomally encoded genes of the bla OXY-2 genotype, and by multilocus sequence typing, most belonged to sequence type 2 (ST2). Carbapenemase genes were carried by IncL, IncHI2, IncFII, IncN, IncC, and IncP6 plasmid types. The emergence of CP K. oxytoca was principally due to the spread of VIM-1-and OXA-48-producing isolates in which VIM-1-and OXA-48 were carried by IncL, IncHI2, IncFII, and IncN plasmids. ST2 and the genotype bla OXY-2 predominated among the 12 sequenced isolates.

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Section: Resultssupporting

confidence: 53%

Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016–2017

Pérez-Vázquez

Oteo

Sola‐Campoy

et al. 2019

Antimicrob Agents Chemother

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“…The KPC-type enzyme was first reported in Klebsiella pneumoniae from the southern United States in 2001 30 and now endemic all over the world. 31,32 In China, dissemination of KPC-producing Enterobacteriaceae spp. has been confirmed in Shandong, Zhejiang, Taiwan, and other provinces.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms and Epidemiology of Carbapenem-Resistant Escherichia coli Isolated from Chinese Patients During 2002–2017

Tian¹,

Zheng²,

Sun³

et al. 2020

IDR

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Background: The emergence and spread of carbapenem-resistant Escherichia coli (E. coli) pose a serious threat to human health worldwide. This study aimed to investigate the molecular mechanisms underlying carbapenem resistance and their prevalence among E. coli in China. Methods: A collection of 5796 E. coli clinical isolates were collected from the First Affiliated Hospital of Wenzhou Medical University from 2002 to 2017. Sensitivity to antibiotics was determined using the agar dilution method. The detection of carbapenemases production and the prevalence of resistance-associated genes were investigated through modified carbapenem inactivation method (mCIM), PCR and sequencing. The mutations in outer membrane porins genes (ompC and ompF) were also analyzed by PCR and sequencing assays. The effect of efflux pump mechanism on carbapenem resistance was also tested. E. coli were typed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results: A total of 58 strains (1.0%) of carbapenem-resistant E. coli were identified. The strains carrying bla KPC-2 and bla NDM accounted for 22.4% (13/58) and 51.7% (30/58), respectively. Among bla NDM -positive strains, 27 bla NDM genes were assigned to bla NDM-5 , while the remaining three strains were bla NDM-1 , whereas bla VIM , bla IMP , bla OXA-48 , and bla SHV were not found. The CTX-M-type β-lactamase genes accounted for 96.6% (56/58). In addition, bla TEM-1 genes were identified in 58.6% of tested strains. In carbapenem-resistant isolates, mutations in OmpC (the majority of mutated sites were D192G and Q104_F141del, accounting for 54.5%) and OmpF (large deletions S75_V127del, W83_D135del and Q88_D135del) were detected. Of note, the antibiotic resistance was not associated with overexpression of efflux pump. Moreover, MLST categorized the 58 carbapenem-resistant isolates into 19 different sequence types. PFGE analysis revealed that homology among the carbapenem-resistant isolates was low and sporadic. Conclusion: The bla NDM was the principal resistance mechanism of carbapenem-resistant E. coli in the hospital. bla NDM-5 is becoming a new threat to public health and the alteration of outer membrane porins might help further increase the MIC of carbapenem.

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“…ST147 is a successful clone with worldwide spread, associated with KPC-2-producing K. pneumoniae (33), with NDM-and CTX-M coproducers in the United States (34), and with OXA-48-Kp (29,35), while ST101 has been associated with CTX-M-producing K. pneumoniae in Hungary (36), with KPC-2 in Spain (37) and Italy (38), and with OXA-48 in Europe (8,31,32,35,39,40) and Africa (31), suggesting intercontinental spread.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Extensively Drug-Resistant or Pandrug-Resistant Sequence Type 147 and 101 OXA-48-Producing Klebsiella pneumoniae Causing Bloodstream Infections in Patients in an Intensive Care Unit

Avgoulea

Pilato

Zarkotou

et al. 2018

Antimicrob Agents Chemother

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Carbapenem-resistant causes important health care-associated infections worldwide. An outbreak of sequence type 11 (ST11) OXA-48-producing (OXA-48-Kp) isolates occurred in Tzaneio Hospital in 2012 and was contained until 2014, when OXA-48-Kp reemerged. The present study involved 19 bloodstream infection (BSI) OXA-48-Kp isolates recovered from 19 intensive care unit (ICU) patients hospitalized between August 2014 and July 2016. MICs were determined by broth microdilution. Beta-lactamase genes were detected by PCR. All isolates were typed by pulsed-field gel electrophoresis/multilocus sequence typing (PFGE/MLST), and 10 representative isolates were typed by next-generation sequencing (NGS). Of the 19 study patients, 9 had previous hospitalizations, and 10 carried OXA-48-Kp prior to BSI isolation; median time from ICU admission to BSI was 29 days. Four OXA-48-Kp isolates belonged to PFGE profile A (ST147) and were pandrug resistant (PDR), while 15 isolates exhibited PFGE profile B (ST101) and were extensively drug resistant. Genes detected via NGS resistome analysis accounted for most of the resistance phenotypes, except for tigecycline and fosfomycin. Insertional inactivation of (distinct per clone) conferred colistin resistance in all 19 isolates. NGS single nucleotide polymorphism (SNP) analysis validated the clonal relatedness of the ST147 and ST101 strains and revealed the possible presence of two index ST147 strains and the microevolution of ST101 strains. Distinct, but highly related, IncL OXA-48-encoding plasmid lineages were identified; plasmids of the ST147 strains were identical with the plasmid of ST11 OXA-48-Kp which caused the 2012 outbreak. In conclusion, biclonal circulation of OXA-48-Kp and, alarmingly, emergence of a PDR clone are reported. These observations, along with the challenging phenotypic detection of OXA-48 producers and the high reported transmissibility of, necessitate intensive efforts to prevent their further spread.

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The spread of KPC-producing Enterobacteriaceae in Spain: WGS analysis of the emerging high-risk clones ofKlebsiella pneumoniaeST11/KPC-2, ST101/KPC-2 and ST512/KPC-3

Cited by 66 publications

References 58 publications

Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016–2017

Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016–2017

<p>Molecular Mechanisms and Epidemiology of Carbapenem-Resistant <em>Escherichia coli</em> Isolated from Chinese Patients During 2002–2017</p>

Characterization of Extensively Drug-Resistant or Pandrug-Resistant Sequence Type 147 and 101 OXA-48-Producing Klebsiella pneumoniae Causing Bloodstream Infections in Patients in an Intensive Care Unit

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