Mechanism of Carbapenem Resistance in Enterobacteriaceae, Acinetobacter and Pseudomonas aeruginosa

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: closed (29 February 2024) | Viewed by 8672

Special Issue Editor


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Guest Editor
Department of Medical Microbiology and Immunology, University of Pécs Medical School, 7624 Pecs, Hungary
Interests: molecular epidemiology of various; mostly antibiotic resistant pathogens including methicillin resistant Staphylococcus aureus (MRSA); Acinetobacter baumannii and carbapenem and/or colistin resistant Enterobacteriaceae with focus on the horizontal and clonal spread of these organisms, and studying their virulence

Special Issue Information

Dear Colleagues,

Infections caused by carbapenem-resistant Gram-negative pathogens, i.e., carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and MDR Pseudomonas aeruginosa are listed by the World Health Organization as pathogens of critical priority. Infections caused by such pathogens are difficult to treat, even if we consider the beta-lactam/beta lactamase inhibitor (BL/BLI) drugs and cefiderocol, which were recently introduced into medical practice. This is especially true if the carbapenem resistance is caused by mechanisms that cannot be inhibited by the new BL/BLI antibiotics. Therefore, the exact mechanism of carbapenem resistance and of the molecular epidemiology of carbapenem-resistant Gram-negative pathogens is of utmost importance to preserve the short- and long-term efficacy of the new antibiotics, and to design measures limiting the spread of such organisms.

Manuscripts are invited concerning the following areas of interest:

  • In vitro diagnostic tools for the phenotypic detection of carbapenemase enzymes and carbapenem resistance in Enterobacteriaceae, Acinetobacter spp., and Pseudomonas aeruginosa;
  • Molecular epidemiology of CRE, CRAB, and carbapenem-resistant Pseudomonas aeruginosa;
  • Evaluation of the treatment efficacy of the new beta-lactam/beta lactamase inhibitors or cefiderocol in infections caused by CRE, CRAb and MDR aeruginosa in relation to their resistance mechanisms.

Dr. Ágnes Pál-Sonnevend
Guest Editor

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Keywords

  • gram-negative infections
  • mechanism of carbapenem resistance
  • molecular epidemiology
  • in vitro diagnostic tools
  • antimicrobial treatment
  • beta-lactam/beta lactamase inhibitors
  • cefiderocol

Published Papers (4 papers)

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22 pages, 1722 KiB  
Article
Virulence Characteristics and Molecular Typing of Carbapenem-Resistant ST15 Klebsiella pneumoniae Clinical Isolates, Possessing the K24 Capsular Type
by Marianna Horváth, Tamás Kovács, József Kun, Attila Gyenesei, Ivelina Damjanova, Zoltán Tigyi and György Schneider
Antibiotics 2023, 12(3), 479; https://doi.org/10.3390/antibiotics12030479 - 28 Feb 2023
Cited by 3 | Viewed by 2029
Abstract
Klebsiella pneumoniae is an opportunistic pathogen that frequently causes nosocomial and community-acquired (CA) infections. Until now, a limited number of studies has been focused on the analyses of changes affecting the virulence attributes. Genotypic and phenotypic methods were used to characterise the 39 [...] Read more.
Klebsiella pneumoniae is an opportunistic pathogen that frequently causes nosocomial and community-acquired (CA) infections. Until now, a limited number of studies has been focused on the analyses of changes affecting the virulence attributes. Genotypic and phenotypic methods were used to characterise the 39 clinical K. pneumoniae isolates; all belonged to the pan-drug resistant, widespread clone ST 15 and expressed the K24 capsule. PFGE has revealed that the isolates could be divided into three distinct genomic clusters. All isolates possessed allS and uge genes, known to contribute to the virulence of K. pneumoniae and 10.25% of the isolates showed hypermucoviscosity, 94.87% produced type 1 fimbriae, 92.3% produced type 3 fimbriae, and 92.3% were able to produce biofilm. In vivo persistence could be supported by serum resistance 46.15%, enterobactin (94.87%) and aerobactin (5.12%) production and invasion of the INT407 and T24 cell lines. Sequence analysis of the whole genomes of the four representative strains 11/3, 50/1, 53/2 and 53/3 has revealed high sequence homology to the reference K. pneumoniae strain HS11286. Our results represent the divergence of virulence attributes among the isolates derived from a common ancestor clone ST 15, in an evolutionary process that occurred both in the hospital and in the community. Full article
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16 pages, 4953 KiB  
Article
Antimicrobial Susceptibility and Molecular Features of Colonizing Isolates of Pseudomonas aeruginosa and the Report of a Novel Sequence Type (ST) 3910 from Thailand
by Arnon Chukamnerd, Rattanaruji Pomwised, Sarunyou Chusri, Kamonnut Singkhamanan, Sanicha Chumtong, Kongpop Jeenkeawpiam, Chanida Sakunrang, Kuwanhusna Saroeng, Phanvasri Saengsuwan, Monwadee Wonglapsuwan and Komwit Surachat
Antibiotics 2023, 12(1), 165; https://doi.org/10.3390/antibiotics12010165 - 12 Jan 2023
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Abstract
Pseudomonas aeruginosa is an important pathogen as it can cause hospital-acquired infections. Additionally, it can also colonize in patients and in other various environments. Hence, this study aimed to investigate the antimicrobial susceptibility, and to study the molecular features, of colonizing isolates of [...] Read more.
Pseudomonas aeruginosa is an important pathogen as it can cause hospital-acquired infections. Additionally, it can also colonize in patients and in other various environments. Hence, this study aimed to investigate the antimicrobial susceptibility, and to study the molecular features, of colonizing isolates of P. aeruginosa from Songklanagarind Hospital, Thailand. Genomic DNA extraction, whole-genome sequencing (WGS), and bioinformatics analysis were performed in all studied isolates. The findings demonstrated that the majority of isolates were non-susceptible to colistin and carbapenem. For in silico study, multilocus sequence typing (MLST) revealed one novel sequence type (ST) 3910 and multiple defined STs. The isolates carried several antimicrobial resistance genes (blaOXA-50, aph(3′)-IIb, etc.) and virulence-associated genes (fleN, waaA, etc.). CRISPR-Cas sequences with different spacers and integrated bacteriophage sequences were also identified in these isolates. Very high SNPs were found in the alignments of the novel ST-3910 isolate with other isolates. A comparative genomic analysis exhibited phylogenetic clustering of our colonizing isolates with clinical isolates from many countries. Interestingly, ST-3981, ST-3982, ST-3983, ST-3984, ST-3985, ST-3986, ST-3986, ST-3986, ST-3987, and ST-3988, the new STs from published genomes, were assigned in this study. In conclusion, this WGS data might be useful for tracking the spread of P. aeruginosa colonizing isolates. Full article
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11 pages, 1786 KiB  
Article
Early Years of Carbapenem-Resistant Enterobacterales Epidemic in Abu Dhabi
by Tibor Pál, Aqdas B. Butt, Akela Ghazawi, Jens Thomsen, Tahir A. Rizvi and Ágnes Sonnevend
Antibiotics 2022, 11(10), 1435; https://doi.org/10.3390/antibiotics11101435 - 19 Oct 2022
Cited by 2 | Viewed by 1260
Abstract
Recent studies showed that the current endemic of carbapenem-resistant Enterobacterales (CRE) in the Emirate of Abu Dhabi is dominated by highly resistant Klebsiella pneumoniae clones ST14, ST231, and CC147, respectively. In the absence of continuous, molecular typing-based surveillance, it remained unknown whether they [...] Read more.
Recent studies showed that the current endemic of carbapenem-resistant Enterobacterales (CRE) in the Emirate of Abu Dhabi is dominated by highly resistant Klebsiella pneumoniae clones ST14, ST231, and CC147, respectively. In the absence of continuous, molecular typing-based surveillance, it remained unknown whether they lately emerged and rapidly became dominant, or they had been present from the early years of the endemic. Therefore, antibiotic resistance, the presence of carbapenemase and 16S methylase genes, and the sequence types of CRE strains collected between 2009 and 2015 were compared with those collected between 2018 and 2019. It was found that members of these three clones, particularly those of the most prevalent ST14, started dominating already in the very early years of the CRE outbreak. Furthermore, while severely impacting the overall antibiotic resistance patterns, the effect of these clones was not exclusive: for example, increasing trends of colistin or decreasing rates of tigecycline resistance were also observed among nonclonal isolates. The gradually increasing prevalence of few major, currently dominating clones raises the possibility that timely, systematic, molecular typing-based surveillance could have provided tools to public health authorities for an early interference with the escalation of the local CRE epidemic. Full article
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8 pages, 771 KiB  
Brief Report
Novel Megaplasmid Driving NDM-1-Mediated Carbapenem Resistance in Klebsiella pneumoniae ST1588 in South America
by Mario Quezada-Aguiluz, Andrés Opazo-Capurro, Nilton Lincopan, Fernanda Esposito, Bruna Fuga, Sergio Mella-Montecino, Gisela Riedel, Celia A. Lima, Helia Bello-Toledo, Marcela Cifuentes, Francisco Silva-Ojeda, Boris Barrera, Juan C. Hormazábal and Gerardo González-Rocha
Antibiotics 2022, 11(9), 1207; https://doi.org/10.3390/antibiotics11091207 - 07 Sep 2022
Cited by 2 | Viewed by 2111
Abstract
Carbapenem-resistant Enterobacterales (CRE) is a critical public health problem in South America, where the prevalence of NDM metallo-betalactamases has increased substantially in recent years. In this study, we used whole genome sequencing to characterize a multidrug-resistant (MDR) Klebsiella pneumoniae (UCO-361 strain) clinical isolate [...] Read more.
Carbapenem-resistant Enterobacterales (CRE) is a critical public health problem in South America, where the prevalence of NDM metallo-betalactamases has increased substantially in recent years. In this study, we used whole genome sequencing to characterize a multidrug-resistant (MDR) Klebsiella pneumoniae (UCO-361 strain) clinical isolate from a teaching hospital in Chile. Using long-read (Nanopore) and short-read (Illumina) sequence data, we identified a novel un-typeable megaplasmid (314,976 kb, pNDM-1_UCO-361) carrying the blaNDM-1 carbapenem resistance gene within a Tn3000 transposon. Strikingly, conjugal transfer of pNDM-1_UCO-361 plasmid only occurs at low temperatures with a high frequency of 4.3 × 10−6 transconjugants/receptors at 27 °C. UCO-361 belonged to the ST1588 clone, previously identified in Latin America, and harbored aminoglycoside, extended-spectrum β-lactamases (ESBLs), carbapenem, and quinolone-resistance determinants. These findings suggest that blaNDM-1-bearing megaplasmids can be adapted to carriage by some K. pneumoniae lineages, whereas its conjugation at low temperatures could contribute to rapid dissemination at the human–environmental interface. Full article
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