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Genomic analysis of the initial dissemination of carbapenem-resistant Klebsiella pneumoniae clones in a tertiary hospital.

ABSTRACT: Carbapenem-resistant Klebsiella pneumoniae is a major cause of hospital-acquired infections and the fastest-growing pathogen in Europe. Carbapenem resistance was detected at the Consorcio Hospital General Universitario de Valencia (CHGUV) in early 2015, and there has been a significant increase in carbapenem-resistant isolates since then. In this study, we collected carbapenem-resistant isolates from this hospital during the period of increase (from 2015 to 2019) and studied how K. pneumoniae carbapenem-resistant isolates emerged and spread in the hospital. A total of 225 isolates were subjected to whole-genome sequencing with Illumina NextSeq. We characterized the isolates by identifying lineages and antimicrobial resistance genes and plasmids, especially those related to reduced carbapenem susceptibility. Our findings show that the initial carbapenem resistance emergence and dissemination at the CHGUV occurred during a short period of 1 year. Furthermore, it was complex, involving six different lineages of types ST307, ST11, ST101 and ST437, different resistance-determinant factors, including OXA-48, NDM-1, NDM-23 and DHA-1, and different plasmids.

SUBMITTER: Garcia-Gonzalez N

PROVIDER: S-EPMC10327503 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Genomic analysis of the initial dissemination of carbapenem-resistant Klebsiella pneumoniae clones in a tertiary hospital.

Garcia-Gonzalez Neris N Fuster Begoña B Tormo Nuria N Salvador Carme C Gimeno Concepcion C Gonzalez-Candelas Fernando F

Microbial genomics 20230601 6

Carbapenem-resistant Klebsiella pneumoniae is a major cause of hospital-acquired infections and the fastest-growing pathogen in Europe. Carbapenem resistance was detected at the Consorcio Hospital General Universitario de Valencia (CHGUV) in early 2015, and there has been a significant increase in carbapenem-resistant isolates since then. In this study, we collected carbapenem-resistant isolates from this hospital during the period of increase (from 2015 to 2019) and studied how K. pne ...[more]

PMID: 37272914

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Project description:BackgroundOngoing studies have revealed the global prevalence of severe infections caused by the hypervirulent strains of Klebsiella pneumoniae (K. pneumoniae). Meanwhile, the World Health Organization and the Centers for Disease Control declared carbapenem-resistant K. pneumoniae as an urgent public health threat, requiring swift and effective action to mitigate its spread. Low- and middle-income countries are severely impacted by such devastating infectious diseases owing to the ill implementation of antimicrobial practices and infection control policies. Having both hypervirulence and carbapenemase gene determinants, the emergence of convergent hypervirulent carbapenem-resistant K. pneumoniae is now being reported worldwide.MethodsIn this study, we sequenced 19 carbapenemase-producing K. pneumoniae strains recovered from various clinical specimens. Additionally, we evaluated the phenotypic antimicrobial susceptibility to multiple antimicrobial classes using the VITEK2 automated system. Utilizing the sequencing data, we characterized the sequence types, serotypes, pangenome, resistance profiles, virulence profiles, and mobile genetic elements of the examined isolates. We highlighted the emergence of high-risk clones carrying hypervirulence genetic determinants among the screened isolates.ResultsOur findings revealed that all carbapenem-resistant isolates exhibited either extensive- or pan-drug resistance and harbored multiple variants of resistance genes spanning nearly all the antimicrobial classes. The most prevalent carbapenemase genes detected within the isolates were blaNDM-5 and blaOXA-48. We identified high-risk clones, such as ST383-K30, ST147-K64, ST11-K15, and ST14-K2, which may have evolved into putative convergent strains by acquiring the full set of hypervirulence-associated genetic determinants (iucABCD, rmpA and/ or rmpA2, putative transporter peg-344). Additionally, this study identified ST709-K9 as a high-risk clone for the first time and uncovered that capsule types K15 and K9 carried hypervirulence genetic determinants. The most frequent Inc types found in these isolates were Col440I, IncHI1B, and Inc FII(K).ConclusionThis study highlights the emergence of high-risk, extensively carbapenem-resistant K. pneumoniae strains co-carrying hypervirulence determinants in Egyptian clinical settings. This poses an imminent threat not only to Egypt but also to the global community, underscoring the urgent need for enhanced surveillance and control strategies to combat this pathogen.

Project description:Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global public health threat. In this study, we employed whole-genome sequencing (WGS) to determine the genomic epidemiology of a longitudinal collection of clinical CRKP isolates recovered from a large public acute care hospital in Singapore. Phylogenetic analyses, a characterization of resistance and virulence determinants, and plasmid profiling were performed for 575 unique CRKP isolates collected between 2009 and 2020. The phylogenetic analyses identified the presence of global high-risk clones among the CRKP population (clonal group [CG] 14/15, CG17/20, CG147, CG258, and sequence type [ST] 231), and these clones constituted 50% of the isolates. Carbapenemase production was common (n = 497, 86.4%), and KPC was the predominant carbapenemase (n = 235, 40.9%), followed by OXA-48-like (n = 128, 22.3%) and NDM (n = 93, 16.2%). Hypervirulence was detected in 59 (10.3%) isolates and was most common in the ST231 carbapenemase-producing isolates (21/59, 35.6%). Carbapenemase genes were associated with diverse plasmid replicons; however, there was an association of blaOXA-181/232 with ColKP3 plasmids. This study presents the complex and diverse epidemiology of the CRKP strains circulating in Singapore. Our study highlights the utility of WGS-based genomic surveillance in tracking the population dynamics of CRKP. IMPORTANCE In this study, we characterized carbapenem-resistant Klebsiella pneumoniae clinical isolates collected over a 12-year period in the largest public acute-care hospital in Singapore using whole-genome sequencing. The results of this study demonstrate significant genomic diversity with the presence of well-known epidemic, multidrug-resistant clones amid a diverse pool of nonepidemic lineages. Genomic surveillance involving comprehensive resistance, virulence, and plasmid gene content profiling provided critical information for antimicrobial resistance monitoring and highlighted future surveillance priorities, such as the emergence of ST231 K. pneumoniae strains bearing multidrug resistance, virulence elements, and the potential plasmid-mediated transmission of the blaOXA-48-like gene. The findings here also reinforce the necessity of unique infection control and prevention strategies that take the genomic diversity of local circulating strains into consideration.

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.

Project description:Multidrug-resistant gram-negative bacteria, such as carbapenem and colistin-resistant Klebsiella pneumoniae (ColR-CRKP), represent a major problem for health systems worldwide and have high lethality. This study investigated the genetic relationship, antimicrobial susceptibility profile, and resistance mechanisms to ColR-CRKP isolates from patients infected/colonized in a tertiary hospital in Salvador, Bahia/Brazil. From September 2016 to January 2018, 46 patients (56 ColR-CRKP positive cultures) were enrolled in the investigation but clinical and demographic data were obtained from 31 patients. Most of them were men (67.7%) and elderly (median age of 62 years old), and the median Charlson score was 3. The main comorbidities were systemic arterial hypertension (38.7%), diabetes (32.2%), and cerebrovascular disease (25.8%). The average hospitalization stay until ColR-CRKP identification in days were 35.12. A total of 90.6% used mechanical ventilation and 93.7% used a central venous catheter. Of the 31 patients who had the data evaluated, 12 had ColR-CRKP infection, and seven died (58.4%). Previous use of polymyxins was identified in 32.2% of the cases, and carbapenems were identified in 70.9%. The minimum inhibitory concentration (MIC) for colistin was > 16 μg/mL, with more than half of the isolates (55%) having a MIC of 256 μg/mL. The bla KPC gene was detected in 94.7% of the isolates, bla NDM in 16.0%, and bla GES in 1.7%. The bla OXA-48, bla VIM, and bla IMP genes were not detected. The mcr-1 test was negative in all 56 isolates. Alteration of the mgrB gene was detected in 87.5% (n = 49/56) of the isolates, and of these, 49.0% (24/49) had alteration in size probably due to IS903B, 22.4% (11/49) did not have the mgrB gene detected, 20.4% (10/49) presented the IS903B, 6.1% (3/49) had a premature stop codon (Q30*), and 2.1% (1/49) presented a thymine deletion at position 104 - 104delT (F35fs). The PFGE profile showed a monoclonal profile in 84.7% of the isolates in different hospital sectors, with ST11 (CC-258) being the most frequent sequence type. This study presents a prolonged outbreak of ColR-CRKP in which 83.9% of the isolates belonged to the same cluster, and 67.6% of the patients evaluated had not used polymyxin, suggesting the possibility of cross-transmission of ColR-CRKP isolates.

Dataset Information

Genomic analysis of the initial dissemination of carbapenem-resistant Klebsiella pneumoniae clones in a tertiary hospital.

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Genomic analysis of the initial dissemination of carbapenem-resistant <i>Klebsiella pneumoniae</i> clones in a tertiary hospital.

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