scholarly journals The Co-occurrence of NDM-5, MCR-1, and FosA3-Encoding Plasmids Contributed to the Generation of Extensively Drug-Resistant Klebsiella pneumoniae

2022 ◽  
Vol 12 ◽  
Author(s):  
Ying Zhou ◽  
Wenxiu Ai ◽  
Yanhua Cao ◽  
Yinjuan Guo ◽  
Xiaocui Wu ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Efflux Pumps ◽  
Drug Resistant ◽  
E Coli ◽  
Extensively Drug Resistant ◽  
Antimicrobial Resistance Genes ◽  
Rnd Efflux Pumps ◽  
Comparative Genetic Analysis ◽  
High Level ◽  
Almost All

The rise and global dissemination of extensively drug-resistant (XDR) bacteria are often related to plasmid-borne mobile antimicrobial resistance genes. Notably, isolates having multiple plasmids are often highly resistant to almost all the antibiotics available. In this study, we characterized an extensively drug-resistant Klebsiella pneumoniae 1678, which exhibited high-level resistance to almost all the available antibiotics. Through whole-genome sequencing (WGS), more than 20 resistant elements and 5 resistant plasmids were observed. Notably, the tigecycline resistance of K. pneumoniae 1678 was not related to the plasmid-borne tetA gene but associated with the overexpression of AcrAB and OqxAB efflux pumps, according to the susceptibility results of tetA-transformant and the related mRNA quantification of RND efflux pumps. Except for tigecycline resistance, three plasmids, mediating resistance to colistin, Fosfomycin, and ceftazidime–avibactam, respectively, were focused. Detailed comparative genetic analysis showed that all these plasmids belonged to dominated epidemic plasmids, and harbored completed conjugation systems. Results of conjugation assay indicated that these three plasmids not only could transfer to E. coli J53 with high conjugation frequencies, respectively, but also could co-transfer to E. coli J53 effectively, which was additionally confirmed by the S1-PFGE plasmids profile. Moreover, multiple insertion sequences (IS) and transposons (Tn) were also found surrounding the vital resistant genes, which may form several novel mechanisms involved in the resistant determinants’ mobilization. Overall, we characterized and reported the uncommon co-existence and co-transferring of FosA3-, NDM-5, and MCR-1-encoding plasmids in a K. pneumoniae isolate, which may increase the risk of spread of these resistant phenotypes and needing great concern.

scholarly journals Genome reconstruction and characterisation of extensively drug-resistant bacterial pathogens through direct metagenomic sequencing of human faeces

2017 ◽  
Author(s):  
Andre Mu ◽  
Jason C. Kwong ◽  
Nicole S. Isles ◽  
Anders Gonçalves da Silva ◽  
Mark B. Schultz ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Sample ◽  
Microbial Pathogens ◽  
Resistant Bacteria ◽  
Metagenomic Sequencing ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Culture Independent ◽  
High Level

AbstractWhole-genome sequencing of microbial pathogens is revolutionising modern approaches to outbreaks of infectious diseases and is reliant upon organism culture. Culture-independent methods have shown promise in identifying pathogens, but high level reconstruction of microbial genomes from microbiologically complex samples for more in-depth analyses remains a challenge. Here, using metagenomic sequencing of a human faecal sample and analysis by tetranucleotide frequency profiling projected onto emergent self-organising maps, we were able to reconstruct the underlying populations of two extensively-drug resistant pathogens, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium. From these genomes, we were able to ascertain molecular typing results, such as MLST, and identify highly discriminatory mutations in the metagenome to distinguish closely related strains. These proof-of-principle results demonstrate the utility of clinical sample metagenomics to recover sequences of important drug-resistant bacteria and application of the approach in outbreak investigations, independent of the need to culture the organisms.

scholarly journals An unequivocal superbug: PDR Klebsiella pneumoniae with an arsenal of resistance and virulence factor genes

2021 ◽  
Vol 15 (03) ◽  
pp. 404-414
Author(s):  
Ahmad Sleiman ◽  
Bassel Awada ◽  
Michele Mocadie ◽  
Nour Sherri ◽  
Louis-Patrick Haraoui ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Virulence Factor ◽  
Molecular Mechanisms ◽  
Whole Genome Sequence ◽  
Drug Resistant ◽  
Type Iv ◽  
Antimicrobial Resistance Genes ◽  
Life Threatening ◽  
High Level ◽  
Virulence Factor Genes

Introduction: Infections caused by extensively-drug resistant (XDR) and pan-drug resistant (PDR) Klebsiella pneumoniae represent an emerging threat due to the high associated mortality. This study aimed to characterize two carbapenem resistant K. pneumoniae strains from the same patient, the first being PDR (referred to as IMP 1078b) and the second being XDR (referred to IMP 1078s) isolated from the same patient. Methodology: Antimicrobial susceptibility testing was done for the 2 K. pneumoniae isolates, followed by carbapenem/β-lactamase inhibitor combination assay, and fitness cost against cefepime and meropenem. Then, whole-genome sequence analysis was performed to decipher the molecular mechanisms behind the high level of resistance recorded in both isolates. Finally, qRT-PCR was done for β-lactam resistant genes. Results: This is the first report about a K. pneumoniae isolate harboring 47 antimicrobial resistance genes and having type IV pilli (Yersinia) and the fimbrial adherence determinant Stb (Salmonella) as virulence factors. Further analysis on both isolates are discussed within the article. Conclusion: The co-existence of a high number of antimicrobial resistant (AMR) genes and virulence factor genes may lead to a life threatening invasive and untreatable infection.

scholarly journals Emergence of High Level Carbapenem and Extensively Drug Resistant Escherichia coli ST746 Producing NDM-5 in Influent of Wastewater Treatment Plant, Seoul, South Korea

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanseob Shin ◽  
Yeonghyeon Kim ◽  
Dukki Han ◽  
Hor-Gil Hur
Keyword(s):  
Escherichia Coli ◽  
Wastewater Treatment ◽  
South Korea ◽  
Resistance Genes ◽  
Treatment Plant ◽  
Carbapenem Resistance ◽  
Drug Resistant ◽  
E Coli ◽  
Extensively Drug Resistant ◽  
High Level

High level carbapenem and extensively drug resistant (XDR) Escherichia coli strain N7, which produces a variant of New Delhi metallo-β-lactamase (NDM-5), was isolated from the influent of the Jungnang wastewater treatment plant located on Han River, Seoul, South Korea. Phenotypic and genotypic resistances to carbapenem were tested using agar and broth dilution methods, and polymerase chain reaction. Whole-genome sequencing was performed to characterize the genetic structure of strain N7. E. coli strain N7, which harbors the blaNDM–5 gene, showed high level of carbapenem resistance at concentrations of doripenem (512 mg/L) and meropenem (256 mg/L), and XDR to 15 antibiotics. Based on the genomic sequence analysis, two plasmids, a hybrid IncHI2/N-type and an IncX3 type, were present. The former contains a cluster (blaNDM–5-bleMBL-trpF-dsbD) bracketed by multi-insertional sequences, IS3000, ISAba125, IS5, and IS26. The latter carries the following resistance genes: blaCTX–14, aac(3)-IV, aadA1, aadA2, aph(3′)-Ia, aph(4)-Ia, sul1, sul2, sul3, dfrA12, fosA3, oqxA, oqxB, mph(A), and floR, and cmlA1. The chromosome, contig3, and contig5 also carry blaCTX–64 and mdf(A), tet(A), and erm(B), tet(M) and aadA22, respectively. Strain N7 also harbors virulence factors such as fimH, flu, ecpABCDE, sfmA, hlyE, and gadA. This study demonstrates the emergence of high level carbapenem resistant XDR E. coli strain N7 containing blaNDM–5 in aquatic environment, Seoul, South Korea. Due to the presence of mobile genetic elements, this strain could horizontally transfer resistance genes, including blaNDM–5 to environmental bacteria. Thus, it is necessary to conduct continuous surveillance for carbapenem resistance in various aquatic environments.

scholarly journals Multidrug-Resistant Klebsiella Pneumoniae: A Retrospective Study in Manaus, Brazil

2021 ◽  
Author(s):  
Rafael Nakamura-Silva ◽  
Louise Cerdeira ◽  
Mariana Oliveira-Silva ◽  
Karen Regina Carim da Costa ◽  
Elder Sano ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Antimicrobial Resistance Genes ◽  
Northern Brazil ◽  
The City

Abstract Klebsiella pneumoniae is an opportunistic pathogen that can cause several infections, mainly in hospitalised or immunocompromised individuals. The spread of K. pneumoniae emerging virulent and multidrug-resistant clones is a worldwide concern and its identification is crucial to control these strains especially in hospitals. This article reports data related to multi-resistant K. pneumoniae strains, isolated from inpatients in the city of Manaus, Brazil, harbouring virulence and antimicrobial resistance genes, including high-risk international clones belonging to clonal group (CG) 258. Twenty-one strains isolated from different patients admitted to four hospitals in the city of Manaus, located in the state of Amazonas, Northern Brazil (Amazon Rainforest region) were evaluated. The majority of strains (61.9 % n = 13) were classified as multidrug-resistant (MDR), and five strains (23.8 %) as extensively drug-resistant (XDR). Several virulence and antimicrobial resistance genes were found among the strains and eight strains (38.1 %) presented the hypermucoviscous phenotype. MLST analysis demonstrated a great diversity of STs among the strains, totaling 12 different STs (ST11, ST23, ST198, ST277, ST307, ST340, ST378, ST462, ST502, ST3991, ST3993 and ST5209). Four of these (ST11, ST23, ST307 and ST340) belong to CG258.

scholarly journals Genomic insights into multi-drug and extensively drug resistant Klebsiella pneumoniae from India

2020 ◽  
Vol 101 ◽  
pp. 12-13
Author(s):  
C. Shankar ◽  
P. Mathur ◽  
J.J. Jacob ◽  
C. Rodrigues ◽  
K. Walia ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals 1675. Epidemiology of Urinary Tract Infections in the United States, 2009 - 2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S823-S823
Author(s):  
Kendra Foster ◽  
Linnea A Polgreen ◽  
Brett Faine ◽  
Philip M Polgreen
Keyword(s):  
United States ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Antibiotic Use ◽  
The United States ◽  
Drug Resistant ◽  
E Coli ◽  
Tract Infections

Abstract Background Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting. Methods We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization. Results There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively. Conclusion E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common. Disclosures All Authors: No reported disclosures

Two high-risk clones of carbapenemase-producing Klebsiella pneumoniae that cause infections in pets and are present in the environment of a veterinary referral hospital

2021 ◽  
Author(s):  
Michael Brilhante ◽  
Stefanie Gobeli Brawand ◽  
Andrea Endimiani ◽  
Helene Rohrbach ◽  
Sonja Kittl ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Genetic Relationships ◽  
Clinical Environment ◽  
Structural Variations ◽  
Veterinary Clinic ◽  
Antimicrobial Resistance Genes ◽  
Carbapenemase Gene ◽  
Genetic Features ◽  
Almost All

Abstract Objectives Infections with carbapenem-resistant Enterobacterales (CRE) are an emerging problem in pets and a major threat to public health. We determined the genetic relationships among carbapenemase-producing Klebsiella pneumoniae (CPKp) strains causing infections in hospitalized pets in a veterinary clinic and those found in the environment. Methods WGS was performed with both the Illumina and Nanopore platforms. Searches of genetic features were performed using several databases and bioinformatics tools, and phylogeny was assessed by whole-genome MLST (wgMLST) using SeqSphere and SNP calling with Snippy. Results WGS analysis of the CPKp strains identified all environmental and almost all animal strains as the high-risk clone ST11, with the exception of two strains that belonged to ST307. All CPKp belonged to novel complex types (CTs) and carried a conjugative 63 kb IncL plasmid encoding the carbapenemase gene blaOXA-48, yersiniabactin and other virulence factors. Although all CPKp ST11 strains carried additional similar IncR plasmids harbouring multiple antimicrobial resistance genes (ARGs), such as the plasmid-mediated blaDHA-1 AmpC gene, some structural variations were observed. The two ST307 strains carried identical 156 kb MDR IncFIB(K) plasmids with several ARGs, including the blaCTX-M-15 ESBL gene. Both wgMLST and cgSNP analysis confirmed that CPKp strains of the same ST were genetically highly related independent of the source of isolation. Conclusions This study demonstrated that the clinical CPKp strains were highly related to those contaminating the clinical environment. These findings confirmed nosocomial spread and highlight veterinary hospitals as a source of CPKp, which may further spread to animals, the environment and humans.

scholarly journals Extensively Drug-Resistant Hypervirulent Klebsiella pneumoniae From a Series of Neonatal Sepsis in a Tertiary Care Hospital, India

2021 ◽  
Vol 8 ◽  
Author(s):  
Tuhina Banerjee ◽  
Jayalaxmi Wangkheimayum ◽  
Swati Sharma ◽  
Ashok Kumar ◽  
Amitabha Bhattacharjee
Keyword(s):  
Klebsiella Pneumoniae ◽  
Neonatal Sepsis ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Plasmid Profile ◽  
Care Hospital ◽  
Drug Resistant ◽  
Maternal Complications ◽  
Extensively Drug Resistant ◽  
Recent Emergence

The recent emergence of multidrug-resistant (MDR) Klebsiella pneumoniae with hypervirulent traits causing severe infections and considerable mortality is a global cause for concern. The challenges posed by these hypermucoviscous strains of K. pneumoniae with regard to their optimal treatment, management, and control policies are yet to be answered. We studied a series of extensively drug-resistant (XDR) and hypervirulent K. pneumoniae ST5235 isolates with resistance to carbapenems and polymyxins causing neonatal sepsis in a tertiary care hospital in India. A total of 9 K. pneumoniae isolates from 9 cases of neonatal sepsis were studied with respect to their clinical relevance, antimicrobial susceptibility profile, presence of extended spectrum β lactamase (ESBL) production, and responsible genes, carbapenemases (classes A, B, and D), and aminoglycoside-resistant genes. Hypervirulence genes encoding hypermucoid nature, iron uptake, and siderophores were detected by multiplex PCR. The plasmid profile was studied by replicon typing. Isolates were typed by multilocus sequence typing (MLST) and enterobacterial repetitive intergenic consensus (ERIC) PCR to study the sequence types (STs) and clonal relation, respectively. The neonates in the studied cases had history of pre-maturity or low birth weight with maternal complications. All the cases were empirically treated with piperacillin–tazobactam and amikacin followed by imipenem/meropenem and vancomycin and polymyxin B as a last resort. However, all the neonates finally succumbed to the condition (100%). The studied isolates were XDR including resistance to polymyxins harboring multiple ESBL genes and carbapenemase genes (blaNDM and blaOXA−48). Hypervirulence genes were present in various combinations with rmpA/A2 genes present in all the isolates. IncFI plasmids were detected in these isolates. All belonged to ST5235. In ERIC PCR, 6 different clusters were seen. The study highlighted the emergence and burden of XDR hypervirulent isolates of K. pneumoniae causing neonatal sepsis in a tertiary care hospital.

scholarly journals High-Level Carbapenem Resistance among OXA-48-Producing Klebsiella pneumoniae with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1174
Author(s):  
Pilar Lumbreras-Iglesias ◽  
M. Rosario Rodicio ◽  
Pablo Valledor ◽  
Tomás Suárez-Zarracina ◽  
Javier Fernández
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Inhibition Zone ◽  
Operating Characteristics ◽  
Outer Membrane Porin ◽  
Antimicrobial Resistance Genes ◽  
Disk Diffusion Assay ◽  
Performance Ability ◽  
High Level

The aim of this work was to analyze outer membrane porin-encoding genes (ompK35 and ompK36) in a collection of OXA-48 producing Klebsiella pneumoniae, to assess the effect of porin alterations on the susceptibility to ceftazidime/avibactam, and to describe a screening methodology for phenotypic detection of OXA-48-producing K. pneumoniae with disrupted porins. Antimicrobial susceptibility was tested by Microscan and Etest. The genomes of 81 OXA-48-producing K. pneumoniae were sequenced. MLST, detection of antimicrobial resistance genes, and analysis of ompK35 and ompK36 were performed in silico. Tridimensional structures of the OmpK36 variants were assessed. Receiver operating characteristics curves were built to visualize the performance ability of a disk diffusion assay using carbapenems and cefoxitin to detect OmpK36 functional alterations. A wide variety of OmpK36 alterations were detected in 17 OXA-48-producing K. pneumoniae isolates. All displayed a high-level meropenem resistance (MIC ≥ 8 mg/L), and some belonged to high-risk clones, such as ST15 and ST147. Alterations in ompK35 were also observed, but they did not correlate with high-level meropenem resistance. All isolates were susceptible to ceftazidime/avibactam and porin alterations did not affect the MICs of the latter combination. Cefoxitin together with ertapenem/meropenem low inhibition zone diameters (equal or lower than 16 mm) could strongly suggest alterations affecting OmpK36 in OXA-48-producing K. pneumoniae. OXA-48-producing K. pneumoniae with porin disruptions are a cause of concern; ceftazidime/avibactam showed good in vitro activity against them, so this combination could be positioned as the choice therapy to combat the infections caused by this difficult-to-treat isolates.

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