A novel #plasmid-encoded #mcr-4.3 gene in a #colistin-resistant #Acinetobacter baumannii clinical strain (J Antimicrob Chemother., abstract)

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

A novel plasmid-encoded mcr-4.3 gene in a colistin-resistant Acinetobacter baumannii clinical strain

Natacha Martins-Sorenson, Erik Snesrud, Danilo Elias Xavier, Luciana Camila Cacci, Anthony T Iavarone, Patrick McGann, Lee W Riley, Beatriz Meurer Moreira

Journal of Antimicrobial Chemotherapy, dkz413, https://doi.org/10.1093/jac/dkz413

Published: 03 October 2019

 

Abstract

Objectives

To identify the molecular mechanism of colistin resistance in an MDR Acinetobacter baumannii clinical strain isolated in 2008 from a meningitis case in Brazil.

Methods

Long- and short-read WGS was used to identify colistin resistance genes in A. baumannii strain 597A with a colistin MIC of 64 mg/L. MS was used to analyse lipid A content. mcr was cloned into pET-26b (+) and transformed into Escherichia coli BL21(λDE3)pLysS for analysis.

Results

A novel plasmid (pAb-MCR4.3) harbouring mcr-4.3 within a Tn3-like transposon was identified. The A. baumannii 597A lipid A MS spectra showed a main molecular ion peak at m/z = 2034, which indicated the addition of phosphoethanolamine to the lipid A structure. E. coli BL21 transformed with pET-26b-mcr-4.3 gained colistin resistance with a colistin MIC of 8 mg/L.

Conclusions

Colistin resistance in A. baumannii 597A was correlated with the presence of a novel plasmid-encoded mcr-4.3 gene.

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; MCR4; Colistin; Acinetobacter baumannii; Brazil.

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#Colistin #resistance-mediated #bacterial surface #modification sensitizes #phage infection (Antimicrob Agents Chemother., abstract)

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

Colistin-resistance-mediated bacterial surface modification sensitizes phage infection

Guijuan Hao, Annie I. Chen, Ming Liu, Haijian Zhou, Marisa Egan, Xiaoman Yang, Biao Kan, Hui Wang, Mark Goulian, Jun Zhu

DOI: 10.1128/AAC.01609-19

 

ABSTRACT

Colistin is a drug of last resort for the treatment of many multidrug resistant Gram-negative bacteria, including Klebsiella pneumoniae. However, bacteria readily acquire resistance to this antibiotic via lipopolysaccharide modifications caused by spontaneous mutations or from enzymes acquired by lateral gene transfer. The fitness cost associated with these modifications remains poorly understood. In this study, we show that colistin-resistant K. pneumoniae are more susceptible to killing by a newly isolated lytic phage than the colistin sensitive parent strain. We observe this behavior for colistin-resistance conferred by a horizontally transferred mcr-1 containing plasmid and also from the inactivation of the chromosomal gene mgrB. By measuring zeta potentials, we found that the phage particles were negatively charged at neutral pH and that colistin-resistant bacteria had less negative zeta potentials than did wildtype. These results suggest that the decreased negative surface charge of colistin-resistant cells lowers the electrostatic repulsion between the phage and bacteria, thereby promoting phage adherence and subsequent infection. To further explore this, we tested the effect of phage treatment on K. pneumoniae growing in several different environments. We found that colistin-resistant cells were more susceptible to phage than were the wildtype cells when growing in biofilms or infected moth larvae and when colonizing the mammalian gut. A better understanding of these fitness costs may lead to new treatment approaches that minimize the emergence and spread of colistin-resistant pathogens in human and environmental reservoirs.

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

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1; Klebsiella pneumoniae; Bacteriophages.

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A ten-year review of #ESBL and non-ESBL #Escherichia coli #bloodstream #infections among #children at a tertiary referral #hospital in South Africa [#ZA] (PLoS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

A ten-year review of ESBL and non-ESBL Escherichia coli bloodstream infections among children at a tertiary referral hospital in South Africa

Oliver Ombeva Malande , James Nuttall, Vashini Pillay, Colleen Bamford, Brian Eley

Published: September 24, 2019 / DOI: https://doi.org/10.1371/journal.pone.0222675

 

Abstract

Introduction

There are few studies describing Escherichia coli (E. coli) bloodstream infection (BSI) among children in Africa, yet E.coli is increasing in importance as a cause of antibiotic resistant infection in paediatric settings.

Methods

In this retrospective, descriptive study aspects of E. coli BSI epidemiology are described over a 10-year period including incidence risk, risk factors for extended-spectrum β-lactamase (ESBL)-producing E. coli BSI, antibiotic susceptibility of the bacterial isolates and outcome including risk factors for severe disease.

Results

There were 583 new E. coli BSI episodes among 217,483 admissions, an overall incidence risk of 2.7 events/1,000 hospital admissions. Of 455 of these E. coli BSI episodes that were analysed, 136 (29.9%) were caused by ESBL-producing isolates. Risk factors for ESBL-producing E. coli BSI included hospitalization in the 28-day period preceding E. coli BSI episodes, having an underlying chronic illness other than HIV infection at the time of the E. coli BSI and having a temperature of 38° Celsius or higher at the time of the E. coli BSI. None of the E. coli isolates were resistant to carbapenems or colistin. The mortality rate was 5.9% and admission to the intensive care unit was required in 12.3% of BSI episodes. Predictors of severe disease included age less than 1 month, hospitalization in the 28-day period preceding E. coli BSI and BSI without a definable focus.

Conclusions

These findings extend our understanding of E. coli BSI in a sub-Saharan African setting, provide useful information that can guide empiric treatment choices for community- and hospital-acquired BSI and help inform prevention strategies.

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Citation: Malande OO, Nuttall J, Pillay V, Bamford C, Eley B (2019) A ten-year review of ESBL and non-ESBL Escherichia coli bloodstream infections among children at a tertiary referral hospital in South Africa. PLoS ONE 14(9): e0222675. https://doi.org/10.1371/journal.pone.0222675

Editor: Surbhi Leekha, University of Maryland School of Medicine, UNITED STATES

Received: April 30, 2019; Accepted: September 3, 2019; Published: September 24, 2019

Copyright: © 2019 Malande et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: There was no special funding for this work, except patient folders and clinical records and staff input from the Red Cross Hospital Children’s Hospital – Paediatric infectious Diseases unit and University of Cape Town.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Antibiotics; Drugs Resistance; E. Coli; Carbapenem; Colistin; Beta-lactams; Bacteremia; Pediatrics; South Africa.

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Conjugative IncX 1 #plasmid harboring #colistin #resistance gene #mcr-5.1 in #E coli isolated from #chicken rice retailed in #Singapore (Antimicrob Agents Chemother., abstract)

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

Conjugative IncX 1 plasmid harboring colistin resistance gene mcr-5.1 in E. coli isolated from chicken rice retailed in Singapore

Siyao Guo, Moon Y.F. Tay, Aung Kyaw Thu, Kelyn Lee Ghee Seow, Yang Zhong, Lee Ching Ng, Joergen Schlundt

DOI: 10.1128/AAC.01043-19

 

ABSTRACT

Colistin is regarded as one of the last resort antimicrobials to Gram-negative bacterial infection (1).…

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

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR5; Plasmids; Food Safety; Singapore.

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#Control and #Elimination of #XDR #Acinetobacter baumanii in an #ICU (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 10—October 2019 / Dispatch

Control and Elimination of Extensively Drug-Resistant Acinetobacter baumanii in an Intensive Care Unit

Amanda Chamieh1, Tania Dagher Nawfal1, Tala Ballouz1, Claude Afif, George Juvelekian, Sani Hlais, Jean-Marc Rolain, and Eid Azar

Author affiliations: University of Balamand, Beirut, Lebanon (A. Chamieh, T. Ballouz, C. Afif, G. Juvelekian, E. Azar); Aix-Marseille University, Marseille, France (T.D. Nawfal, J.-M. Rolain); Saint Joseph University and American University of Beirut, Beirut (S. Hlais)

 

Abstract

We decreased antimicrobial drug consumption in an intensive care unit in Lebanon by changing to colistin monotherapy for extensively drug-resistant Acinetobacter baumanii infections. We saw a 78% decrease of A. baumanii in sputum and near-elimination of blaoxa-23-carrying sequence type 2 clone over the 1-year study. Non–A. baumanii multidrug-resistant infections remained stable.

Keywords: Antibiotics; Drugs Resistance; Colistin; Acinetobacter baumannii; Lebanon; ICU.

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Detection of a novel #mcr-5.4 gene variant in #hospital tap #water by shotgun #metagenomic sequencing (J Antimicrob Chemother., summary)

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

Detection of a novel mcr-5.4 gene variant in hospital tap water by shotgun metagenomic sequencing

Giuseppe Fleres, Natacha Couto, Leonard Schuele, Monika A Chlebowicz,Catarina I Mendes, Luc W M van der Sluis, John W A Rossen, Alex W Friedrich,Silvia García-Cobos

Journal of Antimicrobial Chemotherapy, dkz363, https://doi.org/10.1093/jac/dkz363

Published: 23 August 2019

Issue Section: Research letter

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Sir,

Colistin is considered a last-resort antibiotic for treating serious infections caused by MDR Gram-negative bacteria. The efficacy of this antibiotic is challenged by the emergence and global spread of mobile colistin resistance (mcr) determinants, which threaten human, animal and environmental health. The first mobile colistin resistance gene (mcr-1) was reported in 2015 and since then up to eight different variants have been described.1 In 2017, Borowiak et al.2 described a new transposon-associated phosphoethanolamine transferase mediating colistin resistance, named mcr-5, in d-tartrate-fermenting Salmonella enterica subsp. enterica serovar Paratyphi B isolated from poultry. The mcr-5.3 variant has been recently reported in Stenotrophomonas spp. from sewage water.3 Here we report for the first time (to the best of our knowledge) the detection of an mcr-5 gene in a hospital water environment using short-read metagenomic sequencing (SRMseq) and subsequent characterization using long-read metagenomic sequencing (LRMseq) to reveal its genetic environment.

(…)

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Acknowledgements

We would like to thank Erwin C. Raangs for technical assistance.

Funding

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 713660 (MSCA-COFUND-2015-DP ‘Pronkjewail’), which includes in-kind contributions by commercial partners. None of the commercial partners had any influence on interpretation of reviewed data and conclusions drawn, or on drafting of the manuscript. This work was partly supported by the INTERREG VA (202085)-funded project EurHealth-1Health, part of a Dutch–German cross-border network supported by the European Commission, the Dutch Ministry of Health, Welfare and Sport (VWS), the Ministry of Economy, Innovation, Digitalization and Energy of the German Federal State of North Rhine-Westphalia and the German Federal State of Lower Saxony.

Transparency declarations

None to declare.

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR5; Germany.

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Activity of #imipenem / #relebactam against #carbapenemase-producing #Enterobacteriaceae with high #colistin resistance (J Antimicrob Chemother., abstract)

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

Activity of imipenem/relebactam against carbapenemase-producing Enterobacteriaceae with high colistin resistance

Jessica Carpenter, Nick Neidig, Alex Campbell, Tanner Thornsberry, Taylor Truex,Tiffany Fortney, Yunliang Zhang, Karen Bush

Journal of Antimicrobial Chemotherapy, dkz354, https://doi.org/10.1093/jac/dkz354

Published: 20 August 2019

 

Abstract

Objectives

Imipenem/relebactam, an investigational β-lactam/β-lactamase inhibitor combination for treatment of Gram-negative infections, and comparators including ceftazidime/avibactam, piperacillin/tazobactam and colistin were tested for activity against representative carbapenemase-producing Enterobacteriaceae (CPE) isolates.

Methods

MICs of the antimicrobial agents were determined using standard broth microdilution methodology for CPE isolates collected from Indiana patients, primarily during the time frame of 2013–17 (n = 199 of a total of 200 isolates). Inhibitors were tested at 4 mg/L in all combinations.

Results

Of the CPE in the study, 199 produced plasmid-encoded KPC class A carbapenemases; 1 Serratia marcescens isolate produced the SME-1 chromosomal class A carbapenemase. MIC50/MIC90 values of imipenem/relebactam were ≤0.25/0.5 mg/L, whereas MIC50/MIC90 values of ceftazidime/avibactam were 1/2 mg/L. Resistance to colistin was observed in 54% (n = 97) of 180 non-Serratia isolates tested (MIC50 of 4 mg/L). Colistin resistance mechanisms included production of a plasmid-encoded mcr-1-like gene (n = 2) or an inactivated mgrB gene.

Conclusions

Imipenem/relebactam was the most potent agent tested against CPE in this study and may be a useful addition to the antimicrobial armamentarium to treat infections caused by these pathogens.

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; Carbapenem; Colistin; MCR1; Enterobacteriaceae; Imipenem; Relebactam.

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