Special Issue "Carbapenemase-Producing Enterobacterales"

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editor

Dr. Francesca Andreoni
E-Mail Website
Guest Editor
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy
Interests: antimicrobial resistance; carbapenemase; enterobacteriaceae; molecular typing; plasmid characterization; genetics; molecular biology; identification of vaccine candidates

Special Issue Information

The large family of Enterobacteriaceae includes such species as Klebsiella pneumoniae and Escherichia coli commonly responsible for healthcare infections. The increasing prevalence of resistance to antibiotics used to treat severe infections and diseases, in particular to carbapenems, is due to a rise in multidrug-resistant pathogens which pose an urgent threat to public health. Carbapenem-resistance is mainly associated with the production of carbapenemase—encoded by mobile genetic elements, which are usually plasmids that are horizontally acquired and highly transmissible. Carbapenem-resistant Enterobacteriaceae (CRE) are a common cause of infections in both community and healthcare settings. For this reason, the implementation of control measures and screening programs on CRE carriage is an important practical application toward limiting the dissemination of these strains between clinical wards. The focus of this Special Issue includes any aspects concerning plasmid-mediated antimicrobial resistance along with other carbapenem resistance mechanisms. Understanding the prevalence and routes of transmission of CRE is important in developing specific interventions for healthcare facilities. No less important is the general impact of CRE circulation on the environment. It is known that residues of antimicrobials that are widely used in clinical settings and also entering water and soil during intensive breeding create a selective pressure contributing to the increasing antibiotic resistance of microorganisms. In light of this, attention must be focused on carbapenemase testing in order to provide advanced phenotypic and molecular assays for the identification of CRE. Furthermore, the optimization of protocols could be a valid tool for active global surveillance, and from this perspective, the study of resistance mechanisms can provide significant support for the development of new and appropriate antimicrobial molecules. For all of these reasons, the phenomenon of carbapenem-resistance deserves more attention, for the sake of public health.

Dr. Francesca Andreoni
Guest Editor

Manuscript Submission Information

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Keywords

  • Carbapenem resistant Enterobacteriaceae
  • Carbapenemase
  • Active surveillance
  • Infection control
  • epidemilogy typing
  • plasmid typing

Published Papers (7 papers)

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Research

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Article
Molecular Detection of Carbapenemases in Enterobacterales: A Comparison of Real-Time Multiplex PCR and Whole-Genome Sequencing
Antibiotics 2021, 10(6), 726; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060726 - 16 Jun 2021
Viewed by 333
Abstract
Carbapenem-resistant Enterobacterales are a growing problem in healthcare systems worldwide. While whole-genome sequencing (WGS) has become a powerful tool for analyzing transmission and possible outbreaks, it remains laborious, and the limitations in diagnostic workflows are not well studied. The aim of this study [...] Read more.
Carbapenem-resistant Enterobacterales are a growing problem in healthcare systems worldwide. While whole-genome sequencing (WGS) has become a powerful tool for analyzing transmission and possible outbreaks, it remains laborious, and the limitations in diagnostic workflows are not well studied. The aim of this study was to compare the performance of WGS and real-time multiplex PCR (RT-qPCR) for diagnosing carbapenem-resistant Enterobacterales. In this study, we analyzed 92 phenotypically carbapenem-resistant Enterobacterales, sent to the University Hospital Heidelberg in 2019, by the carbapenem inactivation method (CIM) and compared WGS and RT-qPCR as genotypic carbapenemase detection methods. In total, 80.4% of the collected isolates were identified as carbapenemase producers. For six isolates, discordant results were recorded for WGS, PCR and CIM, as the carbapenemase genes were initially not detected by WGS. A reanalysis using raw reads, rather than assembly, highlighted a coverage issue with failure to detect carbapenemases located in contigs with a coverage lower than 10×, which were then discarded. Our study shows that multiplex RT-qPCR and CIM can be a simple alternative to WGS for basic surveillance of carbapenemase-producing Enterobacterales. Using WGS in clinical workflow has some limitations, especially regarding coverage and sensitivity. We demonstrate that antimicrobial resistance gene detection should be performed on the raw reads or non-curated draft genome to increase sensitivity. Full article
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
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Article
Carriage of Carbapenem-Resistant Enterobacterales in Adult Patients Admitted to a University Hospital in Italy
Antibiotics 2021, 10(1), 61; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010061 - 10 Jan 2021
Cited by 2 | Viewed by 782
Abstract
The emerging spread of carbapenemase-producing Enterobacterales (CPE) strains, in particular, Klebsiella pneumoniae and Escherichia coli, has become a significant threat to hospitalized patients. Carbapenemase genes are frequently located on plasmids than can be exchanged among clonal strains, increasing the antibiotic resistance rate. [...] Read more.
The emerging spread of carbapenemase-producing Enterobacterales (CPE) strains, in particular, Klebsiella pneumoniae and Escherichia coli, has become a significant threat to hospitalized patients. Carbapenemase genes are frequently located on plasmids than can be exchanged among clonal strains, increasing the antibiotic resistance rate. The aim of this study was to determine the prevalence of CPE in patients upon their admission and to analyze selected associated factors. An investigation of the antibiotic resistance and genetic features of circulating CPE was carried out. Phenotypic tests and molecular typing were performed on 48 carbapenemase-producing strains of K. pneumoniae and E. coli collected from rectal swabs of adult patients. Carbapenem-resistance was confirmed by PCR detection of resistance genes. All strains were analyzed by PCR-based replicon typing (PBRT) and multilocus sequence typing (MLST) was performed on a representative isolate of each PBRT profile. More than 50% of the strains were found to be multidrug-resistant, and the blaKPC gene was detected in all the isolates with the exception of an E. coli strain. A multireplicon status was observed, and the most prevalent profile was FIIK, FIB KQ (33%). MLST analysis revealed the prevalence of sequence type 512 (ST512). This study highlights the importance of screening patients upon their admission to limit the spread of CRE in hospitals. Full article
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
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Article
Phenotypic and Genotypic Features of Klebsiella pneumoniae Harboring Carbapenemases in Egypt: OXA-48-Like Carbapenemases as an Investigated Model
Antibiotics 2020, 9(12), 852; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120852 - 28 Nov 2020
Cited by 3 | Viewed by 882
Abstract
This study aimed at the characterization of carbapenem-resistant Klebsiella pneumoniae isolates focusing on typing of the blaOXA-48-like genes. Additionally, the correlation between the resistance pattern and biofilm formation capacity of the carbapenem-resistant K. pneumoniae isolates was studied. The collected isolates were assessed [...] Read more.
This study aimed at the characterization of carbapenem-resistant Klebsiella pneumoniae isolates focusing on typing of the blaOXA-48-like genes. Additionally, the correlation between the resistance pattern and biofilm formation capacity of the carbapenem-resistant K. pneumoniae isolates was studied. The collected isolates were assessed for their antimicrobial resistance and carbapenemases production by a modified Hodge test and inhibitor-based tests. The carbapenemases encoding genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48-like) were detected by PCR. Isolates harboring blaOXA-48-like genes were genotyped by Enterobacterial Repetitive Intergenic Consensus-Polymerase Chain Reaction (ERIC-PCR) and plasmid profile analysis. The discriminatory power of the three typing methods (antibiogram, ERIC-PCR, and plasmid profile analysis) was compared by calculation of Simpson’s Diversity Index (SDI). The transferability of blaOXA-48 gene was tested by chemical transformation. The biofilm formation capacity and the prevalence of the genes encoding the fimbrial adhesins (fimH-1 and mrkD) were investigated. The isolates showed remarkable resistance to β-lactams and non-β-lactams antimicrobials. The coexistence of the investigated carbapenemases encoding genes was prevalent except for only 15 isolates. The plasmid profile analysis had the highest discriminatory power (SDI = 0.98) in comparison with ERIC-PCR (SDI = 0.89) and antibiogram (SDI = 0.78). The transferability of blaOXA-48 gene was unsuccessful. All isolates were biofilm formers with the absence of a significant correlation between the biofilm formation capacity and resistance profile. The genes fimH-1 and mrkD were prevalent among the isolates. The prevalence of carbapenemases encoding genes, especially blaOXA-48-like genes in Egyptian healthcare settings, is worrisome and necessitates further strict dissemination control measures. Full article
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
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Article
Extended Spectrum Beta-Lactamase-Resistant Determinants among Carbapenem-Resistant Enterobacteriaceae from Beef Cattle in the North West Province, South Africa: A Critical Assessment of Their Possible Public Health Implications
Antibiotics 2020, 9(11), 820; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9110820 - 17 Nov 2020
Viewed by 776
Abstract
Carbapenems are considered to be the last resort antibiotics for the treatment of infections caused by extended-spectrum beta-lactamase (ESBL)-producing strains. The purpose of this study was to assess antimicrobial resistance profile of Carbapenem-resistant Enterobacteriaceae (CRE) isolated from cattle faeces and determine the presence [...] Read more.
Carbapenems are considered to be the last resort antibiotics for the treatment of infections caused by extended-spectrum beta-lactamase (ESBL)-producing strains. The purpose of this study was to assess antimicrobial resistance profile of Carbapenem-resistant Enterobacteriaceae (CRE) isolated from cattle faeces and determine the presence of carbapenemase and ESBL encoding genes. A total of 233 faecal samples were collected from cattle and analysed for the presence of CRE. The CRE isolates revealed resistance phenotypes against imipenem (42%), ertapenem (35%), doripenem (30%), meropenem (28%), cefotaxime, (59.6%) aztreonam (54.3%) and cefuroxime (47.7%). Multidrug resistance phenotypes ranged from 1.4 to 27% while multi antibiotic resistance (MAR) index value ranged from 0.23 to 0.69, with an average of 0.40. Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabilis) and Salmonella (34.4, 43.7, 1.3 and 4.6%, respectively) were the most frequented detected species through genus specific PCR analysis. Detection of genes encoding carbapenemase ranged from 3.3% to 35% (blaKPC, blaNDM, blaGES, blaOXA-48, blaVIM and blaOXA-23). Furthermore, CRE isolates harboured ESBL genes (blaSHV (33.1%), blaTEM (22.5%), blaCTX-M (20.5%) and blaOXA (11.3%)). In conclusion, these findings indicate that cattle harbour CRE carrying ESBL determinants and thus, proper hygiene measures must be enforced to mitigate the spread of CRE strains to food products. Full article
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
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Article
Multiplicity of Carbapenemase-Producers Three Years after a KPC-3-Producing K. pneumoniae ST147-K64 Hospital Outbreak
Antibiotics 2020, 9(11), 806; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9110806 - 13 Nov 2020
Viewed by 461
Abstract
Carbapenem resistance rates increased exponentially between 2014 and 2017 in Portugal (~80%), especially in Klebsiella pneumoniae. We characterized the population of carbapanemase-producing Enterobacterales (CPE) infecting or colonizing hospitalized patients (2017–2018) in a central hospital from northern Portugal, where KPC-3-producing K. pneumoniae capsular [...] Read more.
Carbapenem resistance rates increased exponentially between 2014 and 2017 in Portugal (~80%), especially in Klebsiella pneumoniae. We characterized the population of carbapanemase-producing Enterobacterales (CPE) infecting or colonizing hospitalized patients (2017–2018) in a central hospital from northern Portugal, where KPC-3-producing K. pneumoniae capsular type K64 has caused an initial outbreak. We gathered phenotypic (susceptibility data), molecular (population structure, carbapenemase, capsular type) and biochemical (FT-IR) data, together with patients’ clinical and epidemiological information. A high diversity of Enterobacterales species, clones (including E. coli ST131) and carbapenemases (mainly KPC-3 but also OXA-48 and VIM) was identified three years after the onset of carbapenemases spread in the hospital studied. ST147-K64 K. pneumoniae, the initial outbreak clone, is still predominant though other high-risk clones have emerged (e.g., ST307, ST392, ST22), some of them with pandrug resistance profiles. Rectal carriage, previous hospitalization or antibiotherapy were presumptively identified as risk factors for subsequent infection. In addition, our previously described Fourier Transform infrared (FT-IR) spectroscopy method typed 94% of K. pneumoniae isolates with high accuracy (98%), and allowed to identify previously circulating clones. This work highlights an increasing diversity of CPE infecting or colonizing patients in Portugal, despite the infection control measures applied, and the need to improve the accuracy and speed of bacterial strain typing, a goal that can be met by simple and cost-effective FT-IR based typing. Full article
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
Article
Antibiotic Resistance and Mobile Genetic Elements in Extensively Drug-Resistant Klebsiella pneumoniae Sequence Type 147 Recovered from Germany
Antibiotics 2020, 9(10), 675; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9100675 - 05 Oct 2020
Cited by 1 | Viewed by 988
Abstract
Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms [...] Read more.
Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the blaOXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare. Full article
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
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Review

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Review
Molecular Epidemiology of Carbapenemases in Enterobacteriales from Humans, Animals, Food and the Environment
Antibiotics 2020, 9(10), 693; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9100693 - 13 Oct 2020
Cited by 4 | Viewed by 899
Abstract
The Enterobacteriales order consists of seven families including Enterobacteriaceae, Erwiniaceae, Pectobacteriaceae, Yersiniaceae, Hafniaceae, Morganellaceae, and Budviciaceae and 60 genera encompassing over 250 species. The Enterobacteriaceae is currently considered as the most taxonomically diverse among all seven recognized families. The emergence of carbapenem [...] Read more.
The Enterobacteriales order consists of seven families including Enterobacteriaceae, Erwiniaceae, Pectobacteriaceae, Yersiniaceae, Hafniaceae, Morganellaceae, and Budviciaceae and 60 genera encompassing over 250 species. The Enterobacteriaceae is currently considered as the most taxonomically diverse among all seven recognized families. The emergence of carbapenem resistance (CR) in Enterobacteriaceae caused by hydrolytic enzymes called carbapenemases has become a major concern worldwide. Carbapenem-resistant Enterobacteriaceae (CRE) isolates have been reported not only in nosocomial and community-acquired pathogens but also in food-producing animals, companion animals, and the environment. The reported carbapenemases in Enterobacteriaceae from different sources belong to the Ambler class A (blaKPC), class B (blaIMP, blaVIM, blaNDM), and class D (blaOXA-48) β-lactamases. The carbapenem encoding genes are often located on plasmids or associated with various mobile genetic elements (MGEs) like transposons and integrons, which contribute significantly to their spread. These genes are most of the time associated with other antimicrobial resistance genes such as other β-lactamases, as well as aminoglycosides and fluoroquinolones resistance genes leading to multidrug resistance phenotypes. Control strategies to prevent infections due to CRE and their dissemination in human, animal and food have become necessary. Several factors involved in the emergence of CRE have been described. This review mainly focuses on the molecular epidemiology of carbapenemases in members of Enterobacteriaceae family from humans, animals, food and the environment. Full article
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
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