Clinical and Molecular Characteristics of Patients with Bloodstream Infections Caused by KPC and NDM Co-Producing Carbapenem-Resistant <i>Klebsiella pneumoniae</i>

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Abstract

Purpose

Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains.

Methods

A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently.

Results

Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group ( P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%).

Conclusion

In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next “superbug” highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.

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Most cited references 45

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The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

Mervyn Singer, Clifford S Deutschman, Christopher Warren Seymour … (2016)

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.

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Is Open Access

CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database

Brian P. Alcock, Amogelang Raphenya, Tammy Lau … (2019)

Abstract The Comprehensive Antibiotic Resistance Database (CARD; https://card.mcmaster.ca) is a curated resource providing reference DNA and protein sequences, detection models and bioinformatics tools on the molecular basis of bacterial antimicrobial resistance (AMR). CARD focuses on providing high-quality reference data and molecular sequences within a controlled vocabulary, the Antibiotic Resistance Ontology (ARO), designed by the CARD biocuration team to integrate with software development efforts for resistome analysis and prediction, such as CARD’s Resistance Gene Identifier (RGI) software. Since 2017, CARD has expanded through extensive curation of reference sequences, revision of the ontological structure, curation of over 500 new AMR detection models, development of a new classification paradigm and expansion of analytical tools. Most notably, a new Resistomes & Variants module provides analysis and statistical summary of in silico predicted resistance variants from 82 pathogens and over 100 000 genomes. By adding these resistance variants to CARD, we are able to summarize predicted resistance using the information included in CARD, identify trends in AMR mobility and determine previously undescribed and novel resistance variants. Here, we describe updates and recent expansions to CARD and its biocuration process, including new resources for community biocuration of AMR molecular reference data.

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ResFinder 4.0 for predictions of phenotypes from genotypes

Valeria Bortolaia, Rolf S. Kaas, Etienne Ruppé … (2020)

Abstract Objectives WGS-based antimicrobial susceptibility testing (AST) is as reliable as phenotypic AST for several antimicrobial/bacterial species combinations. However, routine use of WGS-based AST is hindered by the need for bioinformatics skills and knowledge of antimicrobial resistance (AMR) determinants to operate the vast majority of tools developed to date. By leveraging on ResFinder and PointFinder, two freely accessible tools that can also assist users without bioinformatics skills, we aimed at increasing their speed and providing an easily interpretable antibiogram as output. Methods The ResFinder code was re-written to process raw reads and use Kmer-based alignment. The existing ResFinder and PointFinder databases were revised and expanded. Additional databases were developed including a genotype-to-phenotype key associating each AMR determinant with a phenotype at the antimicrobial compound level, and species-specific panels for in silico antibiograms. ResFinder 4.0 was validated using Escherichia coli (n = 584), Salmonella spp. (n = 1081), Campylobacter jejuni (n = 239), Enterococcus faecium (n = 106), Enterococcus faecalis (n = 50) and Staphylococcus aureus (n = 163) exhibiting different AST profiles, and from different human and animal sources and geographical origins. Results Genotype–phenotype concordance was ≥95% for 46/51 and 25/32 of the antimicrobial/species combinations evaluated for Gram-negative and Gram-positive bacteria, respectively. When genotype–phenotype concordance was <95%, discrepancies were mainly linked to criteria for interpretation of phenotypic tests and suboptimal sequence quality, and not to ResFinder 4.0 performance. Conclusions WGS-based AST using ResFinder 4.0 provides in silico antibiograms as reliable as those obtained by phenotypic AST at least for the bacterial species/antimicrobial agents of major public health relevance considered.

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Author and article information

Journal

Journal ID (nlm-ta): Infect Drug Resist

Journal ID (iso-abbrev): Infect Drug Resist

Journal ID (publisher-id): idr

Title: Infection and Drug Resistance

Publisher: Dove

ISSN (Electronic): 1178-6973

Publication date (Electronic): 02 May 2024

Publication date Collection: 2024

Volume: 17

Pages: 1685-1697

Affiliations

[1 ]School of Medicine, Southeast University , Nanjing, People’s Republic of China

[2 ]Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University , Nanjing, People’s Republic of China

[3 ]School of Medicine, Nanjing University , Nanjing, People’s Republic of China

[4 ]Nanjing Medical University , Nanjing, People’s Republic of China

Author notes

Correspondence: Xiuwen Wu; Jianan Ren, Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China, Email wuxiuwen@nju.edu.cn; jiananr@nju.edu.cn

[*]

These authors contributed equally to this work

Author information

Jianan Ren http://orcid.org/0000-0002-4697-4762

Article

Publisher ID: 455146

DOI: 10.2147/IDR.S455146

PMC ID: 11073536

PubMed ID: 38711471

SO-VID: e56ebbe2-580e-4d0f-95f4-1f7105149fb0

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 15 December 2023

Date accepted : 22 April 2024

Page count

Figures: 0, Tables: 15, References: 45, Pages: 13

Funding

This work was supported by the National Natural Science Foundation of China (grant number 82272237), Jiangsu Provincial Medical Innovation Center (grant number CXZX202217), and Key Research and Development Program of Jiangsu Province (grant number BE2022823).

Clinical and Molecular Characteristics of Patients with Bloodstream Infections Caused by KPC and NDM Co-Producing Carbapenem-Resistant Klebsiella pneumoniae

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SDG 3: Good Health and Well-Being

Most cited references 45

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database

ResFinder 4.0 for predictions of phenotypes from genotypes

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