Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates.
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ABSTRACT:
SUBMITTER: Kochan TJ
PROVIDER: S-EPMC9263067 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Multidrug-resistant and highly virulent Klebsiella pneumoniae isolates are emerging, but the clonal groups (CGs) corresponding to these high-risk strains have remained imprecisely defined. We aimed to identify K. pneumoniae CGs on the basis of genome-wide sequence variation and to provide a simple bioinformatics tool to extract virulence and resistance gene data from genomic data. We sequenced 48 K. pneumoniae isolates, mostly of serotypes K1 and K2, and compared the genomes with 119 publicly available genomes. A total of 694 highly conserved genes were included in a core-genome multilocus sequence typing scheme, and cluster analysis of the data enabled precise definition of globally distributed hypervirulent and multidrug-resistant CGs. In addition, we created a freely accessible database, BIGSdb-Kp, to enable rapid extraction of medically and epidemiologically relevant information from genomic sequences of K. pneumoniae. Although drug-resistant and virulent K. pneumoniae populations were largely nonoverlapping, isolates with combined virulence and resistance features were detected.
| S-EPMC4214299 | biostudies-literature
Project description:BackgroundIn recent years, the emergence of multidrug resistant hypervirulent K. pneumoniae (MDR hvKp) isolates poses severe therapeutic challenge to global public health. The present study used the complete genome sequence of two MDR hvKp isolates belonging to ST23 to characterize the phylogenetic background and plasmid diversity.MethodsTwo hvKp isolates from patients with bacteremia were sequenced using Ion Torrent PGM and Oxford Nanopore MinION platforms and assembled by hybrid genome assembly approach. Comparative genomics approaches were used to investigate the population structure, evolution, virulence, and antimicrobial resistance of MDR hvKp strains.ResultsThe study isolates exhibited typical features of hvKp phenotypes associated with ST23. The convergence of multidrug resistance and hypervirulence were attributed by the presence of multiple plasmids including a 216 kb virulence plasmid and MDR plasmids belonging to IncA/C2, IncFIB, IncX3, and ColKP3 groups. The insertion of catA1 gene into virulence plasmid was observed along with genetic factors such as aerobactin, salmochelin, and rmpA2 that confer hvKp's hypervirulent phenotype. The core genome single nucleotide polymorphism (SNP) phylogenetic analyses of the isolates showed the evolution of ST23 hvKp was predominantly driven by ICEKp acquisitions.ConclusionTo the best of our knowledge, this is the first report of MDR hvKp isolates of ST23 with insertion of catA1 gene into the virulence plasmid which presents the possibility of hotspot integration sites on the plasmids to aid acquisition of AMR genes. ST23 is no longer confined to susceptible strains of hvKp. Our findings emphasize the need for more studies on recombinant events, plasmid transmission dynamics and evolutionary process involving hvKp.
| S-EPMC7718023 | biostudies-literature
Project description:We describe a case of endogenous endophthalmitis caused by sequence type 66-K2 hypervirulent Klebsiella pneumoniae in a diabetic patient with no travel history outside the United States. Genomic analysis showed the pathogen has remained highly conserved, retaining >98% genetic similarity to the original strain described in Indonesia in 1935.
| S-EPMC8314818 | biostudies-literature
Project description:Since the spread of multidrug-resistant Klebsiella pneumoniae (MDRKP) strains is considered as a challenge for patients with weakened or suppressed immunity, the emergence of isolates carrying determinants of hypervirulent phenotypes in addition may become a serious problem even for healthy individuals. The aim of this study is an investigation of the nonoutbreak K. pneumoniae emergence occurred in early 2017 at a maternity hospital of Kazan, Russia. Ten bacterial isolates demonstrating multiple drug resistance phenotypes were collected from eight healthy full-term breastfed neonates, observed at the maternity hospital of Kazan, Russia. All the infants and their mothers were dismissed without symptoms or complaints, in a satisfactory condition. Whole-genome shotgun (WGS) sequencing was performed with the purpose to track down a possible spread source(s) and obtain detailed information about resistance determinants and pathogenic potential of the collected isolates. Microdilution tests have confirmed production of extended-spectrum ?-lactamases (ESBL) and their resistance to aminoglycoside, ?-lactam, fluoroquinolone, sulfonamide, nitrofurantoin, trimethoprim, and fosfomycin antibiotics and Klebsiella phage. The WGS analysis has revealed the genes that are resistant to aminoglycosides, fluoroquinolones, macrolides, sulfonamides, chloramphenicols, tetracyclines, and trimethoprim and ESBL determinants. The pangenome analysis had split the isolates into two phylogenetic clades. The first group, a more heterogeneous clade, was represented by 5 isolates with 4 different in silico multilocus sequence types (MLSTs). The second group contained 5 isolates from infants born vaginally with the single MLST ST23, positive for genes corresponding to hypervirulent phenotypes: yersiniabactin, aerobactin, salmochelin, colibactin, hypermucoid determinants, and specific alleles of K- and O-antigens. The source of the MDRKP spread was not defined. Infected infants have shown no developed disease symptoms.
| S-EPMC7604597 | biostudies-literature
Project description:Hypervirulent Klebsiella pneumoniae (hvKp) can cause infections in clinically healthy people, such as young and immunocompetent patients. Genes involved in the capsule synthesis or those encoding the siderophores have been adopted as predictors of hvKp. Certain sequence types, such as ST23 and ST86, have been associated with hvKp strains, too. The aim of this study was to investigate the presence of hvKp among 354 K. pneumoniae strains isolated from clinical samples of patients admitted to an Italian 900-bed hospital between 21 May 2021 and April 2022. All the isolates were screened by PCR for the amplification of virulence loci. Whole genome sequencing was performed in strains tested positive for at least one target gene. Thirteen out of 354 (3.7%) were hvKp. Five were wild type and belonged to the hypervirulent clones ST23, ST86, ST5, and ST375 and to the new clone ST6310. Six strains carried the blaKPC gene: three belonged to ST101, two to ST512, and one to ST395. Two isolates were ST147 and carried the blaNDM gene. Although hvKp isolation is not frequent, their presence should be systematically investigated to avoid the spreading of both virulent strains and strains with combined increase in virulence and resistance to antibiotics. PCR-based protocols are essential for surveillance of these strains, which do not always show a recognizable phenotype. Moreover, hvKp strains were isolated also from patients without history of recent foreign travels, indicating an increased spreading of these strains as well as an underestimated of their circulation so far.IMPORTANCEKlebsiella pneumoniae is a healthcare-associated pathogen frequently resistant to antibiotics. Hypervirulent strains of pneumoniae (hvKp) can spread from the primary site of infection to multiple sites causing life-threatening infections also in young otherwise healthy individuals. This study described the isolation of 13 isolates of K. pneumoniae with increased virulence in a large tertiary hospital over a 1-year period. Among them, eight strains were multidrug resistant and hypervirulent. Although these hypervirulent strains are still rare in Italy, their presence is particularly concerning since they can cause difficult-to-treat life-threatening infections. Moreover, not all the hypervirulent isolates were positive by the string test, so hvKp isolates were not always phenotypically detectable. Molecular biology techniques such as PCR amplification and next generation sequencing are therefore necessary for the detection of hvKp isolates, and surveillance programs exploiting molecular techniques are highly desirable.
| S-EPMC10913487 | biostudies-literature
Project description:We report on a carbapenemase-producing hypervirulent Klebsiella pneumoniae (CP-hvKP) isolate collected from a U.S. patient at an outpatient clinic. The isolate was identified as K. pneumoniae serotype K1 sequence type 23 and included both a hypervirulence (with rmpA, rmpA2 iroBCDN, peg-344, and iucABCD-iutA genes) and a carbapenemase-encoding (blaKPC-2) plasmid. The emergence of CP-hvKP underscores the importance of clinical awareness of this pathotype and the need for continued monitoring of CP-hvKP in the United States.
| S-EPMC6591612 | biostudies-literature
Project description:Hypervirulent Klebsiella pneumoniae strains have been increasingly reported worldwide, and there is emergence of carbapenem resistance among them. Here, we report the genome sequences of three carbapenem-resistant hypervirulent K. pneumoniae isolates isolated from bacteremic patients at a tertiary-care center in South India.
| S-EPMC5146430 | biostudies-literature
Project description:Objective:The emergence of carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains poses a significant public threat, and effective antimicrobial therapy is urgently needed. Recent studies indicated that apramycin is a potent antibiotic with good activity against a range of multi-drug resistant pathogens. In this study, we evaluated the in vitro activity of apramycin against clinical CR-hvKp along with carbapenem-resistant non-hvKp (CR-non-hvKp) isolates. Methods:Broth microdilution method was used to evaluate the in vitro activities of apramycin, gentamicin, amikacin, imipenem, meropenem, doripenem, ertapenem and other comparator "last-resort" antimicrobial agents, including ceftazidime-avibactam, colistin and tigecycline, against eighty-four CR-hvKp and forty CR-non-hvKp isolates collected from three Chinese hospitals. Multilocus Sequence typing (MLST), molecular capsule typing (wzi sequencing) and antimicrobial resistance genes were examined by PCR and Sanger sequencing. Pulsed-field gel electrophoresis and next generation sequencing were conducted on selected isolates. Results:Among the 84 CR-hvKp isolates, 97.6, 100, 97.6, and 100% were resistant to imipenem, meropenem, doripenem and ertapenem, respectively. Apramycin demonstrated an MIC50/MIC90 of 4/8 ?g/mL against the CR-hvKp isolates. In contrast, the MIC50/MIC90 for amikacin and gentamicin were >64/>64 ?g/mL. All CR-hvKp isolates were susceptible to ceftazidime-avibactam, colistin and tigecycline with the MIC50/MIC90 values of 0.5/1, 0.25/0.5, 1/1, respectively. For CR-non-hvKp, The MIC50/90 values for apramycin, gentamicin and amikacin were 2/8, >64/>64, and >64/>64 ?g/mL, respectively. There were no statistical significance in the resistance rates of antimicrobial agents between CR-hvKp and CR-non-hvKp groups (p > 0.05). Genetic analysis revealed that all CR-hvKp isolates harbored bla KPC-2, and 94% (n = 79) belong to the ST11 high-risk clone. 93.6% (44/47) of amikacin or gentamicin resistant strains carried 16S rRNA methyltransferases gene rmtB. Conclusion:Apramycin demonstrated potent in vitro activity against CR-hvKp isolates, including those were resistant to amikacin or gentamicin. Further studies are needed to evaluate the applicability of apramycin to be used as a therapeutic antibiotic against CR-hvKp infections.
| S-EPMC7083131 | biostudies-literature
Project description:Sequence type 258 (ST258) is the most widespread multidrug resistant (MDR) Klebsiella pneumoniae strain worldwide. Here, we report the draft genome sequences of two colistin-resistant MDR K. pneumoniae ST258 clinical strains isolated from hospital patients in Italy. These strains are resistant to β-lactams, cephalosporins, fluoroquinolones, aminoglycosides, macrolides, tetracyclines, carbapenems, and colistin.
| S-EPMC3569348 | biostudies-literature
Project description:BackgroundMultidrug-resistant Klebsiella pneumoniae (MDR-KP) are becoming increasingly common over the world. The focus of this research was to get a quantitative assessment of K. pneumoniae and their multidrug resistance (MDR) profile in Nepal.MethodsThree electronic databases: PubMed, Google Scholar, and Research4Life were used to search publications specifying K. pneumoniae infections and/or their MDR status from January 2015 to October 2021. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was followed for the review, and R language 4.1.1 was used for analysis. Depending upon heterogeneity of data, we used random model for pooled data to examine the prevalence of the organism and the multidrug resistance.ResultsEvaluation included 16 studies, and the pooled estimation of K. pneumoniae in total clinical samples was 3% (95% CI; 0.01-0.05). In the meta-analysis, 14 studies were combined for determining the prevalence of K. pneumoniae in total positive clinical isolates which was 16% (95% CI: 0.11-0.20), while from 12 research studies, MDR status in the pathogen was found to be 64% (95% CI, 0.53-0.74).ConclusionThe MDR status of K. pneumoniae as well as the prevalence of the bacteria in Nepal was analyzed which showed alarming situation about administration of antibiotics and indicated choosing and developing reliable antibiotic strategies.
| S-EPMC8888090 | biostudies-literature