Detection of VIM-2-, IMP-1- and NDM-1-producing multidrug-resistant Pseudomonas aeruginosa in Malaysia

doi:10.1016/j.jgar.2018.01.026

Journal of Global Antimicrobial Resistance

Volume 13, June 2018, Pages 271-273

https://doi.org/10.1016/j.jgar.2018.01.026 Get rights and content

Highlights

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First detection of IMP-1- and NDM-1-producing Pseudomonas aeruginosa clinical strains in Malaysia.
•
Identification of three MBL-producing P. aeruginosa (one each with bla_IMP-1, bla_VIM-2 and bla_NDM-1).
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Multidrug resistance was shown by the three MBL-producing P. aeruginosa isolates.
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The MBL-producing P. aeruginosa isolates were classified as ST235 and ST308 by MLST.

Abstract

Objectives

The increasing incidence of carbapenem-resistant Pseudomonas aeruginosa along with the discovery of novel metallo-β-lactamases (MBLs) is of concern. In this study, the isolation of MBL-producing P. aeruginosa clinical strains in Malaysia was investigated.

Methods

A total of 53 P. aeruginosa clinical strains were isolated from different patients in Sultanah Aminah Hospital (Johor Bahru, Malaysia) in 2015. Antimicrobial susceptibility testing was performed, and minimum inhibitory concentrations (MICs) of imipenem and meropenem were determined by Etest. Carbapenem-resistant strains were screened for MBL production by the imipenem–ethylene diamine tetra-acetic acid (IMP-EDTA) double-disk synergy test, MBL imipenem/imipenem-inhibitor (IP/IPI) Etest and PCR. Multilocus sequence typing (MLST) analysis was performed for genotyping of the isolates.

Results

Among the 53 clinical strains, 3 (5.7%) were identified as MBL-producers. Multidrug resistance was observed in all three strains, and two were resistant to all of the antimicrobials tested. Sequencing analysis confirmed that the three strains harboured carbapenemase genes (bla_IMP-1, bla_VIM-2 and bla_NDM-1 in one isolate each). These multidrug-resistant strains were identified as sequence type 235 (ST235) and ST308.

Conclusions

The bla_IMP-1 and bla_NDM-1 genes have not previously been reported in Malaysian P. aeruginosa isolates. The emergence of imipenemase 1 (IMP-1)- and New Delhi metallo-β-lactamase 1 (NDM-1)-producing P. aeruginosa in Malaysia maybe travel-associated.

Introduction

In Southeast Asia, imipenemase 1 (IMP-1)-producing Pseudomonas aeruginosa has been isolated in Singapore and Thailand [1], [2]; Verona integron-borne metallo-β-lactamase 2 (VIM-2)-producing P. aeruginosa has also previously been reported from Malaysia, Thailand and Singapore [2], [3]. The only case of New Delhi metallo-β-lactamase 1 (NDM-1)-producing P. aeruginosa in Southeast Asia was reported from Singapore [4]. We believe this is the first report on the isolation of IMP-1- and NDM-1-producing P. aeruginosa clinical strains in Malaysia.

Section snippets

Methods and results

A total of 53 non-duplicate P. aeruginosa clinical strains isolated from different patients in Sultanah Aminah Hospital (Johor Bahru, Malaysia) in 2015 were investigated. Three carbapenem-resistant strains were identified as metallo-β-lactamase (MBL)-producers (Table 1). Sequence type (ST) analysis was performed by multilocus sequence typing (MLST) according to allelic profiles available in the P. aeruginosa MLST website (http://pubmlst.org/paeruginosa/). The three MBL-producers were identified

Discussion

In Malaysia, only bla_IMP-4, bla_IMP-7 and bla_IMP-26 have been detected in IMP-producing P. aeruginosa [3], [8], [9], [10]. In addition, bla_VIM-2 and bla_VIM-11 have been reported in Malaysian VIM-producing P. aeruginosa [10]. Isolation of bla_NDM-1 was only documented in 7 of 321 Klebsiella pneumoniae clinical strains in a tertiary teaching hospital in Malaysia [11]. Pseudomonadaceae-associated IMP-1 and NDM-1 infection has not been reported locally.

In Southeast Asia, VIM-2-producing P. aeruginosa

Nucleotide accession nos.

The GenBank accession nos. for the sequences of the bla_NDM-1, bla_VIM-2 and bla_IMP-1 genes from strains J11, J20 and J25 are KX987870, KX987868 and KX987869, respectively.

Funding

This work was supported by the University of Malaya (Kuala Lumpur, Malaysia) [postgraduate research grant PG189-2016A].

Competing interests

None declared.

Ethical approval

Not required.

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Dissemination of metallo-β-lactamase-producing Pseudomonas aeruginosa of sequence type 235 in Asian countries
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Molecular characterization of NDM-1 producing Enterobacteriaceae isolates in Singapore hospitals
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Citation Excerpt :
This therapy, if inadequate, is related to a significant increase in mortality. Carbapenem-resistance in P. aeruginosa may be due to the reduction of outer membrane permeability, overexpression of efflux pumps and β-lactamase production.8,10 The blue-carba test differentiates between carbapenemase producers and noncarbapenemase producers (including extended-spectrum-β-lactamase- and/or AmpC-producing isolates), with or without alterations in outer membrane permeability.4
To determine the turnaround time from a blue-carba result until a final microbiological report (bacterial identification plus antimicrobial susceptibility profile) and to infer the impact of an early therapeutic intervention based on the blue-carba results.
Pseudomonas aeruginosa isolates were recovered from hospitalized patients from Porto Alegre, Brazil, and tested by blue-carba test. Time required for a blue-carba result, right after the sample processing, was compared with those required to get final report (specie identification and antimicrobial susceptibility profile) Isolates blue-carba positive were tested by phenotypically and genotypically for Klebsiella pneumoniae carbapenemase and metallo-β-lactamase genes.
A total of 199 isolates were analyzed and 23 (11.6%) were blue-carba positive and harboring the bla_SPM-1-like gene. Fifty-two (26.1%) isolates were blue-carba negative but resistant to meropenem and/or imipenem. Polymyxin B and ceftolozane/tazobactam (this latter except for SPM-1 producers) were 100% active for all P. aeruginosa isolates, a blue-carba test allow an earlier intervention or adequacy of therapy.
Early adequacy can be promoted by blue-carba test for 11.6% of SPM-1-producing P. aeruginosa isolates, polymyxin B could be prior associated and ceftolozane/tazobactam withdrawn from therapy. For the remaining isolates, empirical therapy involving ceftolozane/tazobactam can be maintained with greater likelihood of adequacy. An active communication between laboratory and clinical services is necessary to better explore these earlier blue-carba results, significantly reducing the time for a first intervention.
Pseudomonas aeruginosa epidemic high-risk clones and their association with horizontally-acquired β-lactamases: 2020 update
2020, International Journal of Antimicrobial Agents
Citation Excerpt :
According to their prevalence, global spread and association with MDR/XDR profiles, and specially regarding horizontally-acquired β-lactamases such as ESBLs and carbapenemases, the worldwide top 10 P. aeruginosa high-risk clones includes ST235, ST111, ST233, ST244, ST357, ST308, ST175, ST277, ST654 and ST298. Fig. 1 summarises the main characteristics, including clonal complex (CC), O-antigen serotype, type III secretion system (T3SS) genotype, continents where they have been described and the carbapenemase types detected, of these major high-risk clones, whereas Table 1 details all of their associated acquired β-lactamases and the countries in which they have been described so far, updating the information from a previous 2015 review [9] with the large amount of new data reported in the last 5 years [13–39]. ST235, founder of the CC235 clonal complex, is certainly the most relevant and widespread high-risk clone [39].
Pseudomonas aeruginosa global clones associated with multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes, denominated high-risk clones, are a growing threat in hospitals worldwide. Here we provide a 2020 update on nosocomial MDR/XDR high-risk P. aeruginosa clones. According to their prevalence, global spread and association with MDR/XDR profiles and regarding extended-spectrum β-lactamases (ESBLs) and carbapenemases, the worldwide top 10 P. aeruginosa high-risk clones includes ST235, ST111, ST233, ST244, ST357, ST308, ST175, ST277, ST654 and ST298. ST235 is certainly the most relevant high-risk clone, showing a worldwide dissemination associated with over 60 different β-lactamase variants, including multiple carbapenemases from classes A and B. Moreover, ST235 shows a highly virulent phenotype associated with a high mortality rate, likely due to the production of the ExoU cytotoxin. ST111 and ST233 are also worldwide disseminated MDR/XDR clones, particularly linked to VIM-2 metallo-β-lactamase (MBL), whereas ST244 is a very prevalent clone not always associated with MDR/XDR profiles. ST357, ST308 and ST298 are also exoU+ and are therefore potentially associated with higher virulence. In contrast, ST175, prevalent in some European countries, shows a MDR/XDR phenotype frequently caused by specific chromosomal mutations and is associated with lower virulence. Finally, ST277 is highly prevalent in Brazil and is specifically associated with the SPM MBL. A deeper understanding of the underlying factors driving the success of high-risk clones, including the reported increased capacity for acquiring exogenous determinants, increased spontaneous mutation rates or greater ability to develop biofilms, is required to develop global strategies to combat them.
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Journal of Global Antimicrobial Resistance

Highlights

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Methods and results

Discussion

Nucleotide accession nos.

Funding

Competing interests

Ethical approval

References (17)

Class 1 integron containing metallo β-lactamase gene bla_IMP-1 in carbapenem-resistant Pseudomonas aeruginosa in Thailand

J Infect Chemother

Multiplex PCR for detection of acquired carbapenemase genes

Diagn Microbiol Infect Dis

Spread of the bla_IMP-13 gene in French Pseudomonas aeruginosa through sequence types ST621, ST308 and ST111

Int J Antimicrob Agents

Multilocus sequence types of carbapenem-resistant Pseudomonas aeruginosa in Singapore carrying metallo-β-lactamase genes, including the novel bla_IMP-26 gene

J Clin Microbiol

Dissemination of metallo-β-lactamase-producing Pseudomonas aeruginosa of sequence type 235 in Asian countries

J Antimicrob Chemother

Emergence of a New Delhi metallo-β-lactamase-1-producing Pseudomonas aeruginosa in Singapore

Emerg Microb Infect

Molecular characterization of NDM-1 producing Enterobacteriaceae isolates in Singapore hospitals

West Pac Surveill Response J

Metallo-β-lactamases in clinical Pseudomonas isolates in Taiwan and identification of VIM-3, a novel variant of the VIM-2 enzyme

Antimicrob Agents Chemother

Cited by (23)

Worldwide trend discovery of structural and functional relationship of metallo-β-lactamase for structure-based drug design: A bibliometric evaluation and patent analysis

First report of NDM-1-producing Pseudomonas aeruginosa in the Arabian Peninsula

Impact of the blue-carba rapid test for carbapenemase detection on turnaround time for an early therapy against Pseudomonas aeruginosa

Pseudomonas aeruginosa epidemic high-risk clones and their association with horizontally-acquired β-lactamases: 2020 update

First Detection and Molecular Characterization of Pseudomonas aeruginosa bla<inf>NDM-1</inf> ST308 in Greece

Antimicrobial Resistance, Genetic Lineages, and Biofilm Formation in Pseudomonas aeruginosa Isolated from Human Infections: An Emerging One Health Concern

Short CommunicationDetection of VIM-2-, IMP-1- and NDM-1-producing multidrug-resistant Pseudomonas aeruginosa in Malaysia

Highlights

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Methods and results

Discussion

Nucleotide accession nos.

Funding

Competing interests

Ethical approval

J Infect Chemother

Diagn Microbiol Infect Dis

Int J Antimicrob Agents

Multilocus sequence types of carbapenem-resistant Pseudomonas aeruginosa in Singapore carrying metallo-β-lactamase genes, including the novel blaIMP-26 gene

J Clin Microbiol

Dissemination of metallo-β-lactamase-producing Pseudomonas aeruginosa of sequence type 235 in Asian countries

J Antimicrob Chemother

Emergence of a New Delhi metallo-β-lactamase-1-producing Pseudomonas aeruginosa in Singapore

Emerg Microb Infect

Molecular characterization of NDM-1 producing Enterobacteriaceae isolates in Singapore hospitals

West Pac Surveill Response J

Metallo-β-lactamases in clinical Pseudomonas isolates in Taiwan and identification of VIM-3, a novel variant of the VIM-2 enzyme

Antimicrob Agents Chemother

Short Communication
Detection of VIM-2-, IMP-1- and NDM-1-producing multidrug-resistant Pseudomonas aeruginosa in Malaysia

Multilocus sequence types of carbapenem-resistant Pseudomonas aeruginosa in Singapore carrying metallo-β-lactamase genes, including the novel bla_IMP-26 gene