Prevalence and Some Possible Mechanisms of Colistin Resistance Among Multidrug-Resistant and Extensively Drug-Resistant  Pseudomonas aeruginosa

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Abstract

Background and Aim

The emergence of colistin-resistant strains is considered a great threat for patients with severe infections. Here, we investigate the prevalence and some possible mechanisms of colistin resistance among multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa ( P. aeruginosa).

Methods

Antimicrobial susceptibility was performed using disc diffusion methods while colistin resistance was detected by agar dilution method. Possible mechanisms for colistin resistance were studied by detection of mcr-1 and mcr-2 genes by conventional PCR, detection of efflux mechanisms using Carbonyl Cyanide 3-Chlorophenylhydrazone (CCCP), studying outer membrane protein profile and Lipopolysaccharide (LPS) profile of resistant isolates.

Results

It was found that MDR and XDR represented 96% and 87% of the isolated P. aeruginosa, respectively, and colistin resistance represented 21.3%. No isolates were positive for mcr-2 gene while 50% of colistin-resistant isolates were positive for mcr-1. Efflux mechanisms were detected in 3 isolates. Protein profile showed the presence of a band of 21.4 KDa in the resistant strains which may represent OprH while LPS profile showed differences among colistin-resistant mcr-1 negative strains, colistin-resistant mcr-1 positive strains and susceptible strains.

Conclusion

The current study reports a high prevalence of colistin resistance and mcr-1 gene in P. aeruginosa strains isolated from Egypt that may result in untreatable infections. Our finding makes it urgent to avoid unnecessary clinical use of colistin.

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Most cited references 35

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Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections.

Matthew E. Falagas, Sofia Kasiakou (2005)

The emergence of multidrug-resistant gram-negative bacteria and the lack of new antibiotics to combat them have led to the revival of polymyxins, an old class of cationic, cyclic polypeptide antibiotics. Polymyxin B and polymyxin E (colistin) are the 2 polymyxins used in clinical practice. Most of the reintroduction of polymyxins during the last few years is related to colistin. The polymyxins are active against selected gram-negative bacteria, including Acinetobacter species, Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species. These drugs have been used extensively worldwide for decades for local use. However, parenteral use of these drugs was abandoned approximately 20 years ago in most countries, except for treatment of patients with cystic fibrosis, because of reports of common and serious nephrotoxicity and neurotoxicity. Recent studies of patients who received intravenous polymyxins for the treatment of serious P. aeruginosa and Acinetobacter baumannii infections of various types, including pneumonia, bacteremia, and urinary tract infections, have led to the conclusion that these antibiotics have acceptable effectiveness and considerably less toxicity than was reported in old studies.

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Novel Plasmid-Mediated Colistin Resistance Gene mcr-3 in Escherichia coli

Wenjuan Yin, Hui J. Li, Yingbo Shen … (2017)

ABSTRACT The mobile colistin resistance gene mcr-1 has attracted global attention, as it heralds the breach of polymyxins, one of the last-resort antibiotics for the treatment of severe clinical infections caused by multidrug-resistant Gram-negative bacteria. To date, six slightly different variants of mcr-1, and a second mobile colistin resistance gene, mcr-2, have been reported or annotated in the GenBank database. Here, we characterized a third mobile colistin resistance gene, mcr-3. The gene coexisted with 18 additional resistance determinants in the 261-kb IncHI2-type plasmid pWJ1 from porcine Escherichia coli. mcr-3 showed 45.0% and 47.0% nucleotide sequence identity to mcr-1 and mcr-2, respectively, while the deduced amino acid sequence of MCR-3 showed 99.8 to 100% and 75.6 to 94.8% identity to phosphoethanolamine transferases found in other Enterobacteriaceae species and in 10 Aeromonas species, respectively. pWJ1 was mobilized to an E. coli recipient by conjugation and contained a plasmid backbone similar to those of other mcr-1-carrying plasmids, such as pHNSHP45-2 from the original mcr-1-harboring E. coli strain. Moreover, a truncated transposon element, TnAs2, which was characterized only in Aeromonas salmonicida, was located upstream of mcr-3 in pWJ1. This ΔTnAs2-mcr-3 element was also identified in a shotgun genome sequence of a porcine E. coli isolate from Malaysia, a human Klebsiella pneumoniae isolate from Thailand, and a human Salmonella enterica serovar Typhimurium isolate from the United States. These results suggest the likelihood of a wide dissemination of the novel mobile colistin resistance gene mcr-3 among Enterobacteriaceae and aeromonads; the latter may act as a potential reservoir for mcr-3.

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Novel plasmid-mediated colistin resistance mcr-4 gene in Salmonella and Escherichia coli, Italy 2013, Spain and Belgium, 2015 to 2016

Alessandra Carattoli, Laura Villa, Claudia Feudi … (2017)

A novel mcr colistin resistance gene was identified in a strain of Salmonella enterica, monophasic variant of serovar Typhimurium (4,5,12:i:- ), isolated from a pig at slaughter in Italy in 2013, and in Escherichia coli strains collected during routine diagnostic of post-weaning diarrhoea in pigs from Spain and Belgium in 2015 and 2016. Immediate implementation of mcr-screening including this novel gene variant is required for Salmonella and E. coli from humans and food-producing animals in Europe.

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Author and article information

Journal

Journal ID (nlm-ta): Infect Drug Resist

Journal ID (iso-abbrev): Infect Drug Resist

Journal ID (publisher-id): IDR

Journal ID (pmc): idr

Title: Infection and Drug Resistance

Publisher: Dove

ISSN (Electronic): 1178-6973

Publication date (Electronic): 03 February 2020

Publication date Collection: 2020

Volume: 13

Pages: 323-332

Affiliations

[1 ]Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University , Minia 61519, Egypt

[2 ]Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University , Minia 11566, Egypt

[3 ]Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University , Assiut, Egypt

[4 ]Department of Clinical Pathology, Faculty of Medicine, Assiut University , Assiut, Egypt

[5 ]Sohag General Hospital , Sohag, Egypt

[6 ]Department of Pharmacology, Faculty of Medicine, Assiut University , Assiut, Egypt

[7 ]Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University , Assiut, Egypt

[8 ]Department of Internal Medicine, University of Cincinnati College of Medicine , Cincinnati, OH, USA

Author notes

Correspondence: Helal F Hetta Department of Internal Medicine, University of Cincinnati College of Medicine , PO Box 670595, Cincinnati, OH45267-0595, USA Email helal.hetta@uc.edu

Author information

Rehab M Abd El-Baky http://orcid.org/0000-0001-6094-5653

Azza Elkady http://orcid.org/0000-0001-7727-4868

Helal F Hetta http://orcid.org/0000-0001-8541-7304

Article

Publisher ID: 238811

DOI: 10.2147/IDR.S238811

PMC ID: 7006860

PubMed ID: 32099423

SO-VID: fdcd7dfe-ad76-41cb-b52e-2264c23c8b35

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 15 November 2019

Date accepted : 11 January 2020

Page count

Figures: 5, Tables: 2, References: 47, Pages: 10

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Prevalence and Some Possible Mechanisms of Colistin Resistance Among Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa

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Most cited references 35

Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections.

Novel Plasmid-Mediated Colistin Resistance Gene mcr-3 in Escherichia coli

Novel plasmid-mediated colistin resistance mcr-4 gene in Salmonella and Escherichia coli, Italy 2013, Spain and Belgium, 2015 to 2016

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