Whole-Genome Comparative Analysis of Two Carbapenem-Resistant ST-258 Klebsiella pneumoniae Strains Isolated during a North-Eastern Ohio Outbreak: Differences within the High Heterogeneity Zones.
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SUBMITTER: Ramirez MS
PROVIDER: S-EPMC4943203 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
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Whole-Genome Comparative Analysis of Two Carbapenem-Resistant ST-258 Klebsiella pneumoniae Strains Isolated during a North-Eastern Ohio Outbreak: Differences within the High Heterogeneity Zones.
Ramirez María Soledad MS Xie Gang G Traglia German M GM Johnson Shannon L SL Davenport Karen W KW van Duin David D Ramazani Azam A Perez Federico F Jacobs Michael R MR Sherratt David J DJ Bonomo Robert A RA Chain Patrick S G PS Tolmasky Marcelo E ME
Genome biology and evolution 20160703 6
Klebsiella pneumoniae has become one of the most dangerous causative agents of hospital infections due to the acquisition of resistance to carbapenems, one of the last resort families of antibiotics. Resistance is usually mediated by carbapenemases coded for by different classes of genes. A prolonged outbreak of carbapenem-resistant K. pneumoniae infections has been recently described in northeastern Ohio. Most strains isolated from patients during this outbreak belong to MLST sequence type 258 ...[more]
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Project description:Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has been increasingly reported worldwide. Here, we report an outbreak caused by sequence type 859-K19 (ST859-K19) CR-hvKP isolates in a teaching hospital in China. Interestingly, K. pneumoniae ST859 was a single-locus variant of ST11 but has never been reported before. A total of 11 nonrepetitive ST859 CR-hvKP isolates were collected from 11 patients, 3 of which died of severe CR-hvKP infection. Antimicrobial susceptibility assay results showed that all the 11 CR-hvKP isolates exhibited high-level resistance to commonly used antibiotics, only remaining susceptible to colistin, tigecycline, and ceftazidime/avibactam. Whole-genome sequencing (WGS) was performed using the Illumina platform for the 11 CR-hvKP isolates, and RJ9299 was further sequenced using the PacBio platform. A phylogram tree using WGS data revealed that all the 11 CR-hvKP isolates were clustered in 1 clade, which probably indicated clone transmission. Determinants of resistance and virulence gene analysis using WGS data confirmed the 11 isolates had almost identical resistance gene profiles (blaKPC-2, blaTEM-1B, blaSHV-187, rmtB, fosA6) and virulence gene (rmpA, rmpA2, iucABCDiutA) profiles, which hint at clone spread again. The complete genome size of RJ9299 was 5,875 kb, including a 5,445-kb chromosome, a 215-kb virulence plasmid (pVir-CR-hvKP-RJ9299), a 109-kb blaKPC-2-harboring plasmid (pKPC-2-RJ9299), and three circular plasmids. Comparative genomics showed pVir-RJ9299 (IncHI1B type) and pKPC-2-RJ9299 (IncFII-IncR) possessed over 99% similarity to pLVPK and pKPC-CR-hvKP-C789, respectively. Serum resistance assays and a Galleria mellonella infection model showed the 11 isolates exhibited different levels of virulence. This is the first report of an outbreak caused by ST859 CR-hvKP isolates. IMPORTANCE The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) in China has posed a great threat to public health, especially in the highly transmissible ST11 clone. With the transmission of virulence and resistance determinants, CR-hvKP isolates have been reported in an increasing number of sequence types (STs), including ST23, ST65, ST1797, ST43, ST231, ST147, ST15, ST383, ST268, ST595, ST375, ST48, and ST307. Here, we report an outbreak caused by ST859-K19 CR-hvKP isolates in a teaching hospital in China. ST859 is a single-locus variant of ST11. There is no literature on ST859 K. pneumoniae in public databases, let alone ST859 CR-hvKP isolates. To our knowledge, this is the first report to depict the molecular and genomic characteristics of ST859 CR-hvKP isolates. Active surveillance approaches should be implemented to promptly find the spread of CR-hvKP isolates in health care settings.
| S-EPMC9239081 | biostudies-literature
Project description:Background: The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses an immediate threat to treatment worldwide. This retrospective study assessed the molecular epidemiology and determined the risk factors for and outcomes of CRKP infections in a general teaching hospital in Shanghai, China. Methods: From January 2013 to July 2015, 100 consecutive unique CRKP isolates isolated from hospitalized patients were collected. Isolates were screened for antibiotic resistance genes by polymerase chain reaction and molecular typing was performed by pulsed-field gel electrophoresis (PFGE). Patients infected with CRKP comprised the case group and were compared to the control group of patients infected with carbapenem-susceptible Klebsiella pneumoniae. Therapeutic effects were compared in the CRKP infection group. Results: Among the 100 CRKP isolates, the percentages of multidrug-resistant, extensively drug-resistant (XDR), and pandrug-resistant were 50.0, 50.0, and 0%, respectively. All the CRKP isolates produced KPC-2 and could be divided into 18 PFGE clusters (A-O) and 70 subtypes. No dominant intra-hospital PFGE type was detected using a cutoff of 80% similarity. The ratio of CRKP infection to colonization was 51 to 49. Risk factors correlated with CRKP infection included pulmonary disease (p = 0.038), ICU stay (p = 0.002), invasive ventilation (p = 0.009), blood transfusion (p = 0.028), parenteral nutrition (p = 0.004), sputum suction (p = 0.006), medical history of previous hospitalization (p = 0.022), exposure to antibiotics 90 days before infection (p = 0.030), and antibiotic exposure during hospital stay including carbapenems (p = 0.013), enzyme inhibitors (p = 0.021), nitroimidazoles (p = 0.029), and glycopeptides (p = 0.000). Multivariable analysis showed that sputum suction (odds ratio 3.090, 95% confidence intervals 1.004-9.518, p = 0.049) was an independent risk factor for CRKP infections. Patients infected with CRKP with longer carbapenems treatment course (p = 0.002) showed better outcome. Conclusion: This study showed the severity of CRKP infection in eastern China. Sputum suction was an independent risk factor for CRKP infection. Prolonged duration of treatment with carbapenems benefited the patients infected with CRKP.
| S-EPMC5468447 | biostudies-literature
Project description:Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains belonging to sequence type 258 (ST258) are frequent causes of hospital-associated outbreaks and are a major contributor to the spread of carbapenemases. This genetic lineage emerged several decades ago and remains a major global health care challenge. In this study, genomic epidemiology was used to investigate the emergence, evolution, and persistence of ST258 carbapenem-resistant K. pneumoniae outbreak-causing lineages at a large tertiary care hospital over 8 years. A time-based phylogenetic analysis of 136 ST258 isolates demonstrated the succession of multiple genetically distinct ST258 sublineages over the 8-year period. Ongoing genomic surveillance identified the emergence and persistence of several distinct clonal ST258 populations. Patterns of multidrug resistance determinants and plasmid replicons were consistent with continued evolution and persistence of these populations. Five ST258 outbreaks were documented, including three that were caused by the same clonal lineage. Mutations in genes encoding effectors of biofilm production and iron acquisition were identified among persistent clones. Two emergent lineages bearing K. pneumoniae integrative conjugative element 10 (ICEKp10) and harboring yersiniabactin and colibactin virulence factors were identified. The results show how distinct ST258 subpopulations have evolved and persisted within the same hospital over nearly a decade.IMPORTANCE The carbapenem class of antibiotics is invaluable for the treatment of selected multidrug-resistant Gram-negative pathogens. The continued transmission of carbapenem-resistant bacteria such as ST258 K. pneumoniae is of serious global public health concern, as treatment options for these infections are limited. This genomic epidemiologic investigation traced the natural history of ST258 K. pneumoniae in a single health care setting over nearly a decade. We found that distinct ST258 subpopulations have caused both device-associated and ward-associated outbreaks, and some of these populations remain endemic within our hospital to the present day. The finding of virulence determinants among emergent ST258 clones supports the idea of convergent evolution of drug-resistant and virulent CRKP strains and highlights the need for continued surveillance, prevention, and control efforts to address emergent and evolving ST258 populations in the health care setting.
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