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      Phenotypic and genomic analysis of bacteria from war wounds in Dnipro, Ukraine

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          Abstract

          Objectives

          To better understand the source and potential transmission routes of antibiotic-resistant bacteria infecting injured service members in Ukraine.

          Methods

          Phenotypic and genomic characterizations were performed on 11 Gram-negative pathogens cultured from war wounds at an intermediate evacuation hospital in Dnipro.

          Results

          The analysis revealed both susceptible and extensively drug-resistant strains present in cultures, including high-risk global clones carrying carbapenemases.

          Conclusions

          Globally distributed carbapenemase-producing lineages are being acquired early in the medical evacuation process.

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          Most cited references19

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          A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex

          Klebsiella pneumoniae is a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, and is associated with chronic intestinal diseases. Its diversity and complex population structure pose challenges for analysis and interpretation of K. pneumoniae genome data. Here we introduce Kleborate, a tool for analysing genomes of K. pneumoniae and its associated species complex, which consolidates interrogation of key features of proven clinical importance. Kleborate provides a framework to support genomic surveillance and epidemiology in research, clinical and public health settings. To demonstrate its utility we apply Kleborate to analyse publicly available Klebsiella genomes, including clinical isolates from a pan-European study of carbapenemase-producing Klebsiella , highlighting global trends in AMR and virulence as examples of what could be achieved by applying this genomic framework within more systematic genomic surveillance efforts. We also demonstrate the application of Kleborate to detect and type K. pneumoniae from gut metagenomes. Klebsiella pneumoniae is a pathogen of increasing public health concern and antimicrobial resistance is becoming more prevalent. Here, the authors describe a K. pneumoniae genotyping tool, Kleborate, that can be used to identify lineages and detect antimicrobial resistance and virulence loci.
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            Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131

            ABSTRACT Escherichia coli sequence type 131 (ST131) has emerged globally as the most predominant extraintestinal pathogenic lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined. This study of the largest worldwide collection (n = 215) of sequenced ST131 E. coli isolates to date demonstrates that the clonal expansion of two previously recognized antimicrobial-resistant clades, C1/H30R and C2/H30Rx, started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine. These two clades appear to have emerged in the United States, with the expansion of the C2/H30Rx clade driven by the acquisition of a bla CTX-M-15-containing IncFII-like plasmid that has subsequently undergone extensive rearrangement. Several other evolutionary processes influencing the trajectory of this drug-resistant lineage are described, including sporadic acquisitions of CTX-M resistance plasmids and chromosomal integration of bla CTX-M within subclusters followed by vertical evolution. These processes are also occurring for another family of CTX-M gene variants more recently observed among ST131, the bla CTX-M-14/14-like group. The complexity of the evolutionary history of ST131 has important implications for antimicrobial resistance surveillance, epidemiological analysis, and control of emerging clinical lineages of E. coli. These data also highlight the global imperative to reduce specific antibiotic selection pressures and demonstrate the important and varied roles played by plasmids and other mobile genetic elements in the perpetuation of antimicrobial resistance within lineages.
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              Cefiderocol: Systematic Review of Mechanisms of Resistance, Heteroresistance and In Vivo Emergence of Resistance

              Cefiderocol appears promising, as it can overcome most β-lactam resistance mechanisms (including β-lactamases, porin mutations, and efflux pumps). Resistance is uncommon according to large multinational cohorts, including against isolates resistant to carbapenems, ceftazidime/avibactam, ceftolozane/tazobactam, and colistin. However, alarming proportions of resistance have been reported in some recent cohorts (up to 50%). A systematic review was conducted in PubMed and Scopus from inception to May 2022 to review mechanisms of resistance, prevalence of heteroresistance, and in vivo emergence of resistance to cefiderocol during treatment. A variety of mechanisms, typically acting in concert, have been reported to confer resistance to cefiderocol: β-lactamases (especially NDM, KPC and AmpC variants conferring resistance to ceftazidime/avibactam, OXA-427, and PER- and SHV-type ESBLs), porin mutations, and mutations affecting siderophore receptors, efflux pumps, and target (PBP-3) modifications. Coexpression of multiple β-lactamases, often in combination with permeability defects, appears to be the main mechanism of resistance. Heteroresistance is highly prevalent (especially in A. baumannii), but its clinical impact is unclear, considering that in vivo emergence of resistance appears to be low in clinical studies. Nevertheless, cases of in vivo emerging cefiderocol resistance are increasingly being reported. Continued surveillance of cefiderocol’s activity is important as this agent is introduced in clinical practice.
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                Author and article information

                Contributors
                Journal
                JAC Antimicrob Resist
                JAC Antimicrob Resist
                jacamr
                JAC-Antimicrobial Resistance
                Oxford University Press (UK )
                2632-1823
                June 2024
                13 June 2024
                13 June 2024
                : 6
                : 3
                : dlae090
                Affiliations
                Department of Microbiology, Virology, Immunology, Epidemiology and Biomedical Physics and Informatics, Dnipro State Medical University , Dnipro, Ukraine
                Department of Microbiology, Virology, Immunology, Epidemiology and Biomedical Physics and Informatics, Dnipro State Medical University , Dnipro, Ukraine
                Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research , Silver Spring, MD, USA
                Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research , Silver Spring, MD, USA
                Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research , Silver Spring, MD, USA
                Department of Microbiology, National Pirogov Memorial Medical University , Vinnytsia, Ukraine
                Multidrug-Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research , Silver Spring, MD, USA
                Author notes
                Corresponding author. E-mail: dstepanskiy@ 123456gmail.com @stepanskyi
                Author information
                https://orcid.org/0000-0001-6350-8176
                Article
                dlae090
                10.1093/jacamr/dlae090
                11170486
                38872715
                9af20e26-68e4-4465-915f-f85fa5e0e497
                © The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 April 2024
                : 11 May 2024
                Page count
                Pages: 4
                Funding
                Funded by: U.S. Department of the Army, Operation and Maintenance, Army;
                Categories
                Original Article
                AcademicSubjects/MED00740
                AcademicSubjects/SCI01150

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