Towards #endemicity: large-scale #expansion of the #NDM-1-producing #Klebsiella pneumoniae ST11 lineage in #Poland, 2015–16 (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Towards endemicity: large-scale expansion of the NDM-1-producing Klebsiella pneumoniae ST11 lineage in Poland, 2015–16

A Baraniak, M Machulska, D Żabicka, E Literacka, R Izdebski, P Urbanowicz, K Bojarska,M Herda, A Kozińska, W Hryniewicz, M Gniadkowski, NDM-PL Study Group

Journal of Antimicrobial Chemotherapy, dkz315, https://doi.org/10.1093/jac/dkz315

Published: 13 August 2019

 

Abstract

Objectives

In 2015 and 2016 Poland recorded rapid proliferation of New Delhi MBL (NDM)-producing Enterobacterales, with at least 470 and 1780 cases, respectively. We addressed the roles of the Klebsiella pneumoniae ST11 NDM-1 outbreak genotype, already spreading in 2012–14, and of newly imported organisms in this increase.

Methods

The study included 2136 NDM-positive isolates identified between April 2015 and December 2016, following transfer of patients with K. pneumoniae ST147 NDM-1 from Tunisia to Warsaw in March 2015. The isolates were screened by PCR mapping for variants of blaNDM-carrying Tn125-like elements. Selected isolates were typed by PFGE and MLST. NDM-encoding plasmids were analysed by nuclease S1/hybridization, transfer assays, PCR-based replicon typing and PCR mapping.

Results

The organisms were mainly K. pneumoniae containing the Tn125A variant of the ST11 epidemic lineage (n = 2094; ∼98%). Their representatives were of the outbreak pulsotype and ST11, and produced NDM-1, encoded by specific IncFII (pKPX-1/pB-3002cz)-like plasmids. The isolates were recovered in 145 healthcare centres in 13/16 administrative regions, predominantly the Warsaw area. The ‘Tunisian’ genotype K. pneumoniae ST147 NDM-1 Tn125F comprised 18 isolates (0.8%) from eight institutions. The remaining 24 isolates, mostly K. pneumoniae and Escherichia coli of diverse STs, produced NDM-1 or NDM-5 specified by various Tn125 derivatives and plasmids.

Conclusions

The K. pneumoniae ST11 NDM-1 outbreak has dramatically expanded in Poland since 2012, which may bring about a countrywide endemic situation in the near future. In addition, the so-far limited K. pneumoniae ST147 NDM-1 outbreak plus multiple NDM imports from different countries were observed in 2015–16.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; NDM1; NDM5; Poland.

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#Protein #determinants of #dissemination and host specificity of metallo- #betalactamases (Nat Commun., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Nat Commun. 2019 Aug 9;10(1):3617. doi: 10.1038/s41467-019-11615-w.

Protein determinants of dissemination and host specificity of metallo-β-lactamases.

López C1, Ayala JA2, Bonomo RA3,4,5, González LJ6,7, Vila AJ8,9,10.

Author information: 1 Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), S2000EZP, Rosario, Argentina. 2 Centro de Biología Molecular Severo Ochoa, Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC-UAM), Campus de Cantoblanco, 28049, Madrid, Spain. 3 Medical Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA. 4 Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA. 5 CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, OH, 44106, USA. 6 Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), S2000EZP, Rosario, Argentina. lgonzalez@ibr-conicet.gov.ar. 7 Área Biofísica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, S2002LRK, Rosario, Argentina. lgonzalez@ibr-conicet.gov.ar. 8 Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), S2000EZP, Rosario, Argentina. vila@ibr-conicet.gov.ar. 9 CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, OH, 44106, USA. vila@ibr-conicet.gov.ar. 10 Área Biofísica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, S2002LRK, Rosario, Argentina. vila@ibr-conicet.gov.ar.

 

Abstract

The worldwide dissemination of metallo-β-lactamases (MBLs), mediating resistance to carbapenem antibiotics, is a major public health problem. The extent of dissemination of MBLs such as VIM-2, SPM-1 and NDM among Gram-negative pathogens cannot be explained solely based on the associated mobile genetic elements or the resistance phenotype. Here, we report that MBL host range is determined by the impact of MBL expression on bacterial fitness. The signal peptide sequence of MBLs dictates their adaptability to each host. In uncommon hosts, inefficient processing of MBLs leads to accumulation of toxic intermediates that compromises bacterial growth. This fitness cost explains the exclusion of VIM-2 and SPM-1 from Escherichia coli and Acinetobacter baumannii, and their confinement to Pseudomonas aeruginosa. By contrast, NDMs are expressed without any apparent fitness cost in different bacteria, and are secreted into outer membrane vesicles. We propose that the successful dissemination and adaptation of MBLs to different bacterial hosts depend on protein determinants that enable host adaptability and carbapenem resistance.

PMID: 31399590 DOI: 10.1038/s41467-019-11615-w

Keywords: Antibiotics; Drugs Resistance; Carbapenem; NDM.

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The #antimicrobial #peptide thanatin disrupts the bacterial outer membrane and inactivates the #NDM-1 metallo-β-lactamase (Nat Commun., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Nat Commun. 2019 Aug 6;10(1):3517. doi: 10.1038/s41467-019-11503-3.

The antimicrobial peptide thanatin disrupts the bacterial outer membrane and inactivates the NDM-1 metallo-β-lactamase.

Ma B1, Fang C1, Lu L2, Wang M1, Xue X1, Zhou Y1, Li M1, Hu Y1, Luo X3, Hou Z4.

Author information: 1 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, 710032, China. 2 Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China. 3 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, 710032, China. xxluo3@fmmu.edu.cn. 4 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, 710032, China. hzh_0001@163.com.

 

Abstract

New Delhi metallo-β-lactamase-1 (NDM-1) is the most prevalent type of metallo-β-lactamase and hydrolyzes almost all clinically used β-lactam antibiotics. Here we show that the antimicrobial peptide thanatin disrupts the outer membrane of NDM-1-producing bacteria by competitively displacing divalent cations on the outer membrane and inducing the release of lipopolysaccharides. In addition, thanatin inhibits the enzymatic activity of NDM-1 by displacing zinc ions from the active site, and reverses carbapenem resistance in NDM-1-producing bacteria in vitro and in vivo. Thus, thanatin’s dual mechanism of action may be useful for combating infections caused by NDM-1-producing pathogens.

PMID: 31388008 DOI: 10.1038/s41467-019-11503-3

Keywords: Antibiotics; Drugs Resistance; NDM1; Beta-lactams.

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#Urban brown #rats (Rattus norvegicus) as possible #source of #MDR #Enterobacteriaceae and #MRSA, Vienna, #Austria, 2016 and 2017 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Urban brown rats (Rattus norvegicus) as possible source of multidrug-resistant Enterobacteriaceae and meticillin-resistant Staphylococcus spp., Vienna, Austria, 2016 and 2017

Amélie Desvars-Larrive1, Werner Ruppitsch2, Sarah Lepuschitz2, Michael P Szostak1, Joachim Spergser1, Andrea T Feßler3, Stefan Schwarz3, Stefan Monecke4,5,6, Ralf Ehricht4,6, Chris Walzer1,7, Igor Loncaric1

Affiliations: 1 University of Veterinary Medicine, Vienna, Austria; 2 Austrian Agency for Health and Food Safety, Vienna, Austria; 3 Freie Universität, Berlin, Germany; 4 Leibniz Institute of Photonic Technology (IPHT), Jena, Germany; 5 Technische Universität, Dresden, Germany; 6 InfectoGnostics Research Campus, Jena, Germany; 7 Wildlife Conservation Society, Bronx, New York, United States

Correspondence: Amélie Desvars-Larrive amelie.desvarsvetmeduni.ac.at

Citation style for this article: Desvars-Larrive Amélie, Ruppitsch Werner, Lepuschitz Sarah, Szostak Michael P, Spergser Joachim, Feßler Andrea T, Schwarz Stefan, Monecke Stefan, Ehricht Ralf, Walzer Chris, Loncaric Igor. Urban brown rats (Rattus norvegicus) as possible source of multidrug-resistant Enterobacteriaceae and meticillin-resistant Staphylococcus spp., Vienna, Austria, 2016 and 2017. Euro Surveill. 2019;24(32):pii=1900149. https://doi.org/10.2807/1560-7917.ES.2019.24.32.1900149

Received: 25 Feb 2019;   Accepted: 03 Jun 2019

 

Abstract

Background

Brown rats (Rattus norvegicus) are an important wildlife species in cities, where they live in close proximity to humans. However, few studies have investigated their role as reservoir of antimicrobial-resistant bacteria.

Aim

We intended to determine whether urban rats at two highly frequented sites in Vienna, Austria, carry extended-spectrum β-lactamase-producing Enterobacteriaceae, fluoroquinolone-resistant Enterobacteriaceae and meticillin-resistant (MR) Staphylococcus spp. (MRS).

Methods

We surveyed the presence of antimicrobial resistance in 62 urban brown rats captured in 2016 and 2017 in Vienna, Austria. Intestinal and nasopharyngeal samples were cultured on selective media. We characterised the isolates and their antimicrobial properties using microbiological and genetic methods including disk diffusion, microarray analysis, sequencing, and detection and characterisation of plasmids.

Results

Eight multidrug-resistant Escherichia coli and two extensively drug-resistant New Delhi metallo-β-lactamases-1 (NDM-1)-producing Enterobacter xiangfangensis ST114 (En. cloacae complex) were isolated from nine of 62 rats. Nine Enterobacteriaceae isolates harboured the blaCTX-M gene and one carried a plasmid-encoded ampC gene (blaCMY-2). Forty-four MRS were isolated from 37 rats; they belonged to seven different staphylococcal species: S. fleurettii, S. sciuri, S. aureus, S. pseudintermedius, S. epidermidis, S. haemolyticus (all mecA-positive) and mecC-positive S. xylosus.

Conclusion

Our findings suggest that brown rats in cities are a potential source of multidrug-resistant bacteria, including carbapenem-resistant En. xiangfangensis ST114. Considering the increasing worldwide urbanisation, rodent control remains an important priority for health in modern cities.

© This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Antibiotics; Drugs Resistance; MRSA; Enterobacteriaceae; Wildlife; Austria.

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#Synergistic #combinations and repurposed #antibiotics active against the #pandrug #resistant #Klebsiella pneumoniae #Nevada strain (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Synergistic combinations and repurposed antibiotics active against the pandrug-resistant Klebsiella pneumoniae Nevada strain

Thea Brennan-Krohn [MD], James E. Kirby [MD]

DOI: 10.1128/AAC.01374-19

 

ABSTRACT

In early 2017, the Centers for Disease Control and Prevention issued an alarming report describing a woman in Nevada who died in the setting of infection with a pan-resistant Klebsiella pneumoniae isolate that harbored an NDM-1 enzyme (AR-0636) and was colistin resistant as a result of inactivation of the mgrB regulator gene (1, 2).…

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Klebsiella pneumoniae; USA; Nevada.

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Presence of #NDM in non-E. coli #Enterobacteriaceae in the #poultry #production #environment (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Presence of NDM in non-E. coli Enterobacteriaceae in the poultry production environment

Rongmin Zhang, Jiyun Li, Yang Wang, Jianzhong Shen, Zhangqi Shen, Shaolin Wang

Journal of Antimicrobial Chemotherapy, dkz193, https://doi.org/10.1093/jac/dkz193

Published: 18 May 2019

 

Abstract

Objectives

Characterization of non-Escherichia coli NDM-carrying Enterobacteriaceae in the poultry production environment.

Methods

A total of 36 NDM-positive Enterobacteriaceae (22 Klebsiella pneumoniae, 13 Enterobacter cloacae and 1 Salmonella enterica) were isolated from a chicken farm and WGS was conducted using Illumina Hiseq2500. The genomic characterization of the isolates acquired through WGS analysis included the genomic context-flanking blaNDM genes, MLST, the antibiotic resistance genes (ARGs) and replicon types of plasmids. WGS information for another 73 K. pneumoniae isolates from different sources was retrieved from GenBank and then combined with isolates in this study for comparative genomic and phylogenetic analysis.

Results

Three types of genetic environment carrying blaNDM were identified in 36 non-E. coli Enterobacteriaceae isolates. Sequence comparison analysis indicated these genetic environments were completely identical to our previous findings. WGS further revealed three major types of plasmids (IncFIB, IncX3 and IncFII) from these isolates and the phylogenetic analysis suggested several K. pneumoniae isolates with ST11, ST37 and ST147 from the commercial chicken farm that were closely related to isolates of human origin.

Conclusions

The blaNDM-harbouring genetic contexts were identified not only in E. coli, but also in K. pneumoniae, E. cloacae and S. enterica, which may indicate that blaNDM has been widely disseminated to non-E. coli Enterobacteriaceae species in animal farms. The close relationship of K. pneumoniae isolates from different origins suggests they could serve as a key vehicle for the transfer of ARGs between humans and food animal production environments.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; NDM; Poultry; Food Safety.

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Challenge of drug #resistance in #Pseudomonas aeruginosa: clonal spread of #NDM1-positive ST-308 within a tertiary #hospital (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Challenge of drug resistance in Pseudomonas aeruginosa: clonal spread of NDM-1-positive ST-308 within a tertiary hospital

Ka Lip Chew, Sophie Octavia, Oon Tek Ng, Kalisvar Marimuthu, Indumathi Venkatachalam, Bernadette Cheng, Raymond T P Lin, Jeanette W P Teo

Journal of Antimicrobial Chemotherapy, dkz169, https://doi.org/10.1093/jac/dkz169

Published: 12 May 2019

 

Abstract

Objectives

MDR Pseudomonas aeruginosa is a serious global threat to healthcare institutions. The mechanism by which drug resistance can be acquired is variable, but acquired carbapenemase production has been reported in P. aeruginosa. An investigation was performed to determine the rate and genomic epidemiology of New Delhi MBL (NDM) in β-lactam-non-susceptible isolates.

Methods

P. aeruginosa isolates from a tertiary hospital in Singapore between January 2015 and February 2018 were investigated for the presence of NDM genes.

Results

Out of 298 pan-β-lactam-non-susceptible isolates, 31 were found to be NDM positive (10.4%). WGS demonstrated that all 31 NDM-positive isolates were clonal, belonging to ST-308. blaNDM was chromosomally inserted within an integrative and conjugative element (ICE), ICETn43716385. The NDM-P. aeruginosa isolates possessed an extensive repertoire of both cell-associated [flagella, pili, alginate/biofilm, LPS, type III secretion system (T3SS) and type VI secretion system (T6SS)] and secreted virulence factors. Antibiograms revealed higher rates of drug resistance in NDM-positive isolates compared with their non-NDM counterparts. The NDM isolates remained 100% susceptible only to colistin.

Conclusions

The combination of chromosomal mutations, acquired resistance genes and virulence factors likely facilitated the persistent and ongoing spread of the ST-308 clade of P. aeruginosa within the hospital. Our study illustrates the particular threat of NDM-positive P. aeruginosa in a tertiary hospital setting in the era of antimicrobial resistance.

Topic: pseudomonas aeruginosa – mutation – colistin – epidemiology – drug resistance – alginates – biofilms – bodily secretions – chromosomes – drug resistance, microbial – bacterial fimbria – flagella – genes – genome – lactams – singapore – persistence – virulence factors – antibiogram – resistance genes – type iii protein secretion system complex – whole genome sequencing

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; NDM1; Pseudomonas aeruginosa; Nosocomial outbreaks.

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