An Emerging Clone, Klebsiellapneumoniae Carbapenemase 2–Producing K. pneumoniae Sequence Type 16, Associated With High Mortality Rates in a CC258-Endemic Setting

Andrey, Diego O.; Dantas, Priscila Pereira; Martins, Willames Brasileiro; Carvalho, Fabíola Marques de; Almeida, Luiz Gonzaga Paula de; Sands, Kirsty; Portal, Edward; Sauser, Julien; Cayô, Rodrigo; Nicolás, Marisa Fabiana; Vasconcelos, Ana Tereza Ribeiro de; Medeiros, Eduardo Alexandrino; Walsh, Timothy R.; Gales, Ana Cristina

doi:10.1093/cid/ciz1095

Cited by 54 publications

(55 citation statements)

References 32 publications

(27 reference statements)

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“…The study was approved by the Hospital São Paulo/Federal University of São Paulo (UNIFESP) Ethics Committee for Clinical Research (protocol number 1.814.158). Epidemiological and clinical data were extracted from the medical records in a standardized case form, as previously described (8).…”

Section: Methodsmentioning

confidence: 99%

“…Multilocus sequence type (MLST), antimicrobial resistance (AMR) determinants, and plasmid replicons were identified using the MLST 2.0, ResFinder 3.1, and PlasmidFinder online tools (Center for Genomic Epidemiology) setting cutoff values of 90% identity and 80% minimum coverage (10 September 2018 database) (43). Virulence genes were analyzed with Geneious 10.6.1 using an in-house data set (80% minimal coverage, 75% identity) (8). Assembled genomes were submitted to the Kaptive platform, and capsular loci (KL) were determined using Klebsiella K locus primary as a reference (44).…”

Section: Methodsmentioning

confidence: 99%

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Clinical and Molecular Description of a High-Copy IncQ1 KPC-2 Plasmid Harbored by the International ST15 Klebsiella pneumoniae Clone

Martins

Nicolás

et al. 2020

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This study provides the genomic characterization and clinical description of bloodstream infections (BSI) cases due to ST15 KPC-2 producer Klebsiella pneumoniae. Six KPC-K. pneumoniae isolates were recovered in 2015 in a tertiary Brazilian hospital and were analyzed by whole-genome sequencing (WGS) (Illumina MiSeq short reads). Of these, two isolates were further analyzed by Nanopore MinION sequencing, allowing complete chromosome and plasmid circularization (hybrid assembly), using Unicycler software. The clinical analysis showed that the 30-day overall mortality for these BSI cases was high (83%). The isolates exhibited meropenem resistance (MICs, 32 to 128 mg/liter), with 3/6 isolates resistant to polymyxin B. The conjugative properties of the blaKPC-2 plasmid and its copy number were assessed by standard conjugation experiments and sequence copy number analysis. We identified in all six isolates a small (8.3-kb), high-copy-number (20 copies/cell) non-self-conjugative IncQ plasmid harboring blaKPC-2 in a non-Tn4401 transposon. This plasmid backbone was previously reported to harbor blaKPC-2 only in Brazil, and it could be comobilized at a high frequency (10−4) into Escherichia coli J53 and into several high-risk K. pneumoniae clones (ST258, ST15, and ST101) by a common IncL/M helper plasmid, suggesting the potential of international spread. This study thus identified the international K. pneumoniae ST15 clone as a carrier of blaKPC-2 in a high-copy-number IncQ1 plasmid that is easily transmissible among other common Klebsiella strains. This finding is of concern since IncQ1 plasmids are efficient antimicrobial resistance determinant carriers across Gram-negative species. The spread of such carbapenemase-encoding IncQ1 plasmids should therefore be closely monitored. IMPORTANCE In many parts of the world, carbapenem resistance is a serious public health concern. In Brazil, carbapenem resistance in Enterobacterales is mostly driven by the dissemination of KPC-2-producing K. pneumoniae clones. Despite being endemic in this country, only a few reports providing both clinical and genomic data are available in Brazil, which limit the understanding of the real clinical impact caused by the dissemination of different clones carrying blaKPC-2 in Brazilian hospitals. Although several of these KPC-2-producer K. pneumoniae isolates belong to the clonal complex 258 and carry Tn4401 transposons located on large plasmids, a concomitant emergence and silent dissemination of small high-copy-number blaKPC-2 plasmids are of importance, as described in this study. Our data identify a small high-copy-number IncQ1 KPC plasmid, its clinical relevance, and the potential for conjugative transfer into several K. pneumoniae isolates, belonging to different international lineages, such as ST258, ST101, and ST15.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Clinical and Molecular Description of a High-Copy IncQ1 KPC-2 Plasmid Harbored by the International ST15 Klebsiella pneumoniae Clone

Martins

Nicolás

et al. 2020

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“…The full virulence potential of EC121 was evaluated using the virulence model of G. mellonella, as previously described [80,81]. Briefly, 10 mL of logarithmic phase cultures were washed twice and adjusted to the optical density of 0.7 (O.D.…”

Section: In Vivo Assay In Galleria Mellonella Virulence Modelmentioning

confidence: 99%

Virulence Potential of a Multidrug-Resistant Escherichia coli Strain Belonging to the Emerging Clonal Group ST101-B1 Isolated from Bloodstream Infection

et al. 2020

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Escherichia coli EC121 is a multidrug-resistant (MDR) strain isolated from a bloodstream infection of an inpatient with persistent gastroenteritis and T-zone lymphoma that died due to septic shock. Despite causing an extraintestinal infection, previous studies showed that it did not have the usual characteristics of an extraintestinal pathogenic E. coli. Instead, it belonged to phylogenetic group B1 and harbored few known virulence genes. To evaluate the pathogenic potential of strain EC121, an extensive genome sequencing and in vitro characterization of various pathogenicity-associated properties were performed. The genomic analysis showed that strain EC121 harbors more than 50 complete virulence genetic clusters. It also displays the capacity to adhere to a variety of epithelial cell lineages and invade T24 bladder cells, as well as the ability to form biofilms on abiotic surfaces, and survive the bactericidal serum complement activity. Additionally, EC121 was shown to be virulent in the Galleria mellonella model. Furthermore, EC121 is an MDR strain harboring 14 antimicrobial resistance genes, including blaCTX-M-2. Completing the scenario, it belongs to serotype O154:H25 and to sequence type 101-B1, which has been epidemiologically linked to extraintestinal infections as well as to antimicrobial resistance spread. This study with E. coli strain EC121 shows that clinical isolates considered opportunistic might be true pathogens that go underestimated.

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“…In addition, CRE are also often resistant to unrelated antibacterial classes, such as fluoroquinolones, aminoglycosides, fosfomycin and tigecycline, thus making them XDR and some times PDR 27 . Associated resistance to colistin and tigecycline is linked to worse clinical outcomes 28,29 . In Greece, prevalences of ~30% for XDR and ~5% for PDR have been reported 27 .…”

Section: Carbapenem-resistant Enterobacteralesmentioning

confidence: 99%

“…are already visible: ceftazidime-avibactam is vulnerable to KPC β lactamase mutants with increased hydrolytic capacity for ceftazidime. Such mutants can easily be obtained in vitro 29 and have been selected in patients treated with ceftazidime-avibactam 58 . For ceftolozane-tazobactam, there are reports of in vivo selection of P. aeruginosa mutants with sequence muta tions in AmpC that confer resistance to both ceftolozanetazobactam and ceftazidime-avibactam 31,32 .…”

Section: Wwwnaturecom/nrmicromentioning

confidence: 99%

Critical analysis of antibacterial agents in clinical development

Theuretzbacher¹,

et al. 2020

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| The antibacterial agents currently in clinical development are predominantly derivatives of well-established antibiotic classes and were selected to address the class-specific resistance mechanisms and determinants that were known at the time of their discovery. Many of these agents aim to target the antibiotic-resistant priority pathogens listed by the WHO, including Gram-negative bacteria in the critical priority category, such as carbapenem-resistant Acinetobacter, Pseudomonas and Enterobacterales. Although some current compounds in the pipeline have exhibited increased susceptibility rates in surveillance studies that depend on geography, pre-existing cross-resistance both within and across antibacterial classes limits the activity of many of the new agents against the most extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Gram-negative pathogens. In particular, cross-resistance to unrelated classes may occur by co-selection of resistant strains, thus leading to the rapid emergence and subsequent spread of resistance. There is a continued need for innovation and new-class antibacterial agents in order to provide effective therapeutic options against infections specifically caused by XDR and PDR Gram-negative bacteria. ✉

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An Emerging Clone, Klebsiellapneumoniae Carbapenemase 2–Producing K. pneumoniae Sequence Type 16, Associated With High Mortality Rates in a CC258-Endemic Setting

Cited by 54 publications

References 32 publications

Clinical and Molecular Description of a High-Copy IncQ1 KPC-2 Plasmid Harbored by the International ST15 Klebsiella pneumoniae Clone

Clinical and Molecular Description of a High-Copy IncQ1 KPC-2 Plasmid Harbored by the International ST15 Klebsiella pneumoniae Clone

Virulence Potential of a Multidrug-Resistant Escherichia coli Strain Belonging to the Emerging Clonal Group ST101-B1 Isolated from Bloodstream Infection

Critical analysis of antibacterial agents in clinical development

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