Changes in the #resistance and #epidemiological characteristics of #Pseudomonas aeruginosa during a ten-year period (J Microbiol Immunol Infect., abstract)

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

J Microbiol Immunol Infect. 2019 Sep 30. pii: S1684-1182(19)30153-7. doi: 10.1016/j.jmii.2019.08.017. [Epub ahead of print]

Changes in the resistance and epidemiological characteristics of Pseudomonas aeruginosa during a ten-year period.

Feng W1, Huang Q2, Wang Y1, Yuan Q1, Li X3, Xia P4, Sun F5.

Author information: 1 Department of Pharmacy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. 2 Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. 3 Department of Pharmacy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Department of Pharmacy, Handan Branch of Chinese PLA 980 Hospital, Handan, Hebei province, China. 4 Department of Pharmacy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address: peiyuan_xia2013@163.com. 5 Department of Pharmacy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address: fengj_sun@163.com.

 

Abstract

PURPOSE:

The aim of this study was to investigate the changes over a ten-year period in the resistance and epidemiological characteristics of Pseudomonas aeruginosa strains isolated from the Department of Respiratory in Southwest Hospital.

METHODS:

Antimicrobial resistance was detected using the plate double dilution method. PCR amplification and sequencing were performed to evaluate the carbapenemase genes and the oprD gene. Bacterial genotypes were analyzed by multilocus sequence typing (MLST). Quantitative real-time PCR experiments were performed to assess the expression of efflux pump (mexA and mexX) and ampC gene.

RESULTS:

We collected 233 P. aeruginosa isolates in 2006-2007 and 128 isolates in 2016-2017. The resistance rate of P. aeruginosa strains to the tested antibiotics was significantly lower in 2016-2017 than in 2006-2007. The MLST results showed 27 genotypes in 2006-2007 and 18 genotypes in 2016-2017. ST235 was the most prevalent sequence type, and there was no significant change in the genotypes over the ten-year period. Both VIM-2 and IMP-4 genes were found in 2006-2007, whereas only IMP-4 was found in 2016-2017. The oprD mutational inactivation was the main factor responsible for carbapenem resistance, and the overexpression of mexX had a good correlation with aminoglycoside resistance.

CONCLUSION:

These results indicated that the antibiotic resistance of P. aeruginosa in our respiratory department decreased. The loss of oprD gene was the main mechanism of carbapenem resistance, and mexX overexpression was the major contributing factor to aminoglycoside resistance.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS: Efflux pump; Epidemiology; OprD; Pseudomonas aeruginosa; Resistance

PMID: 31628088 DOI: 10.1016/j.jmii.2019.08.017

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Aminoglycosides; Pseudomonas aeruginosa; China.

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Combination of #Azithromycin and #Gentamicin for Efficient #Treatment of #Pseudomonas aeruginosa Infections (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page. (LINK). Abstract, edited.]

Combination of Azithromycin and Gentamicin for Efficient Treatment of Pseudomonas aeruginosa Infections

Huan Ren, Yiwei Liu, Jingyi Zhou, Yuqing Long, Chang Liu, Bin Xia, Jing Shi, Zheng Fan,Yuying Liang, Shuiping Chen, Jun Xu, Penghua Wang, Yanhong Zhang, Guangbo Zhu,Huimin Liu, Yongxin Jin, Fang Bai, Zhihui Cheng, Shouguang Jin, Weihui Wu

The Journal of Infectious Diseases, jiz341, https://doi.org/10.1093/infdis/jiz341

Published: 16 August 2019

 

Abstract

Background

Trans-translation is a ribosome rescue system that plays an important role in bacterial tolerance to environmental stresses. It is absent in animals, making it a potential treatment target. However, its role in antibiotic tolerance in Pseudomonas aeruginosa remains unknown.

Methods

The role and activity of trans-translation during antibiotic treatment were examined with a trans-translation–deficient strain and a genetically modified trans-translation component gene, respectively. In vitro assays and murine infection models were used to examine the effects of suppression of trans-translation.

Results

We found that the trans-translation system plays an essential role in P. aeruginosa tolerance to azithromycin and multiple aminoglycoside antibiotics. We further demonstrated that gentamicin could suppress the azithromycin-induced activation of trans-translation. Compared with each antibiotic individually, gentamicin and azithromycin combined increased the killing efficacy against planktonic and biofilm-associated P. aeruginosa cells, including a reference strain PA14 and its isogenic carbapenem-resistance oprD mutant, the mucoid strain FRD1, and multiple clinical isolates. Furthermore, the gentamicin-azithromycin resulted in improved bacterial clearance in murine acute pneumonia, biofilm implant, and cutaneous abscess infection models.

Conclusions

Combination treatment with gentamicin and azithromycin is a promising strategy in combating P. aeruginosa infections.

Pseudomonas aeruginosa, trans-translation, azithromycin, antibiotic combination

Topic: antibiotics – pseudomonas aeruginosa – gentamicin sulfate (usp) – azithromycin – biofilms – gentamicins – infection – killing

Issue Section: Major Article

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: 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; Aminoglycosides; Gentamicin; Azithromycin; Pseudomonas aeruginosa; Biofilm.

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De Novo Emergence of #Peptides That Confer #Antibiotic #Resistance (mBio, abstract)

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

De Novo Emergence of Peptides That Confer Antibiotic Resistance

Michael Knopp, Jonina S. Gudmundsdottir, Tobias Nilsson, Finja König, Omar Warsi, Fredrika Rajer, Pia Ädelroth, Dan I. Andersson

Gerard D. Wright, Editor

DOI: 10.1128/mBio.00837-19

 

ABSTRACT

The origin of novel genes and beneficial functions is of fundamental interest in evolutionary biology. New genes can originate from different mechanisms, including horizontal gene transfer, duplication-divergence, and de novo from noncoding DNA sequences. Comparative genomics has generated strong evidence for de novo emergence of genes in various organisms, but experimental demonstration of this process has been limited to localized randomization in preexisting structural scaffolds. This bypasses the basic requirement of de novo gene emergence, i.e., lack of an ancestral gene. We constructed highly diverse plasmid libraries encoding randomly generated open reading frames and expressed them in Escherichia coli to identify short peptides that could confer a beneficial and selectable phenotype in vivo (in a living cell). Selections on antibiotic-containing agar plates resulted in the identification of three peptides that increased aminoglycoside resistance up to 48-fold. Combining genetic and functional analyses, we show that the peptides are highly hydrophobic, and by inserting into the membrane, they reduce membrane potential, decrease aminoglycoside uptake, and thereby confer high-level resistance. This study demonstrates that randomized DNA sequences can encode peptides that confer selective benefits and illustrates how expression of random sequences could spark the origination of new genes. In addition, our results also show that this question can be addressed experimentally by expression of highly diverse sequence libraries and subsequent selection for specific functions, such as resistance to toxic compounds, the ability to rescue auxotrophic/temperature-sensitive mutants, and growth on normally nonused carbon sources, allowing the exploration of many different phenotypes.

 

IMPORTANCE

De novo gene origination from nonfunctional DNA sequences was long assumed to be implausible. However, recent studies have shown that large fractions of genomic noncoding DNA are transcribed and translated, potentially generating new genes. Experimental validation of this process so far has been limited to comparative genomics, in vitroselections, or partial randomizations. Here, we describe selection of novel peptides in vivousing fully random synthetic expression libraries. The peptides confer aminoglycoside resistance by inserting into the bacterial membrane and thereby partly reducing membrane potential and decreasing drug uptake. Our results show that beneficial peptides can be selected from random sequence pools in vivo and support the idea that expression of noncoding sequences could spark the origination of new genes.

Keywords: Antibiotics; Drugs Resistance; Aminoglycosides; Genetics.

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Emergence of #carbapenem resistant #Pseudomonas asiatica producing #NDM-1 and #VIM-2 metallo-β-lactamases in #Myanmar (Antimicrob Agents Chemother., abstract)

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

Emergence of carbapenem-resistant Pseudomonas asiatica producing NDM-1 and VIM-2 metallo-β-lactamases in Myanmar

Mari Tohya, Tatsuya Tada, Shin Watanabe, Kyoko Kuwahara-Arai, Khwar Nyo Zin, Ni Ni Zaw, May Yee Aung, San Mya, Khin Nyein Zan, Teruo Kirikae, Htay Htay Tin

DOI: 10.1128/AAC.00475-19

 

ABSTRACT

Pseudomonas asiatica is recently proposed species of the genus Pseudomonas. This study describes eight isolates of carbapenem-resistant P. asiatica harboring blaNDM-1 and blaVIM-2, genes encoding metallo-β-lactamase (MBL). These isolates were obtained from urine samples of patients hospitalized in Myanmar. These isolates were resistant to carbapenems but susceptible to colistin. All eight isolates were positive for a carbapenemase inactivation method, CIMTrisII, and seven were positive on an immunochromatographic assay for NDM-type MBL. One isolate was highly resistant to aminoglycosides. Whole genome sequencing showed that seven isolates harbored blaNDM-1 and one harbored blaVIM-2, with these genes located on the chromosome. One isolate harbored blaNDM-1 and rmtC, a gene encoding 16S rRNA methylase. Five types of genomic environments surrounding blaNDM-1 and blaVIM-2 were detected in these eight isolates, with four isolates having the same type. These data indicate that P. asiatica harboring genes encoding carbapenemases, including blaNDM-1 and blaVIM-2, are spreading in medical settings in Myanmar.

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

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; Aminoglycosides; Pseudomonas asiatica; Myanmar.

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The use of #aminoglycosides in #animals within the #EU: development of #resistance in animals and possible #impact on #human and animal #health: a review (J Antimicrob Chemother., abstract)

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

The use of aminoglycosides in animals within the EU: development of resistance in animals and possible impact on human and animal health: a review

Engeline van Duijkeren, Christine Schwarz, Damien Bouchard, Boudewijn Catry, Constança Pomba, Keith Edward Baptiste, Miguel A Moreno, Merja Rantala, Modestas Ružauskas, Pascal Sanders, Christopher Teale, Astrid L Wester, Kristine Ignate, Zoltan Kunsagi, Helen Jukes

Journal of Antimicrobial Chemotherapy, dkz161, https://doi.org/10.1093/jac/dkz161

Published: 19 April 2019

 

Abstract

Aminoglycosides (AGs) are important antibacterial agents for the treatment of various infections in humans and animals. Following extensive use of AGs in humans, food-producing animals and companion animals, acquired resistance among human and animal pathogens and commensal bacteria has emerged. Acquired resistance occurs through several mechanisms, but enzymatic inactivation of AGs is the most common one. Resistance genes are often located on mobile genetic elements, facilitating their spread between different bacterial species and between animals and humans. AG resistance has been found in many different bacterial species, including those with zoonotic potential such as Salmonella spp., Campylobacter spp. and livestock-associated MRSA. The highest risk is anticipated from transfer of resistant enterococci or coliforms (Escherichia coli) since infections with these pathogens in humans would potentially be treated with AGs. There is evidence that the use of AGs in human and veterinary medicine is associated with the increased prevalence of resistance. The same resistance genes have been found in isolates from humans and animals. Evaluation of risk factors indicates that the probability of transmission of AG resistance from animals to humans through transfer of zoonotic or commensal foodborne bacteria and/or their mobile genetic elements can be regarded as high, although there are no quantitative data on the actual contribution of animals to AG resistance in human pathogens. Responsible use of AGs is of great importance in order to safeguard their clinical efficacy for human and veterinary medicine.

Issue Section: Review

© 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; Aminoglycosides; Food safety.

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#Spanish nationwide #survey on #Pseudomonas aeruginosa #antimicrobial #resistance mechanisms and #epidemiology (J Antimicrob Chemother., abstract)

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

Spanish nationwide survey on Pseudomonas aeruginosa antimicrobial resistance mechanisms and epidemiology

Ester del Barrio-Tofiño, Laura Zamorano, Sara Cortes-Lara, Carla López-Causapé, Irina Sánchez-Diener, Gabriel Cabot, Germán Bou, Luis Martínez-Martínez, Antonio Oliver

Journal of Antimicrobial Chemotherapy, dkz147, https://doi.org/10.1093/jac/dkz147

Published: 15 April 2019

 

Abstract

Objectives

To undertake a Spanish nationwide survey on Pseudomonas aeruginosamolecular epidemiology and antimicrobial resistance.

Methods

Up to 30 consecutive healthcare-associated P. aeruginosa isolates collected in 2017 from each of 51 hospitals were studied. MICs of 13 antipseudomonal agents were determined by broth microdilution. Horizontally acquired β-lactamases were detected by phenotypic methods and PCR. Clonal epidemiology was evaluated through PFGE and MLST; at least one XDR isolate from each clone and hospital (n = 185) was sequenced.

Results

The most active antipseudomonals against the 1445 isolates studied were colistin and ceftolozane/tazobactam (both 94.6% susceptible, MIC50/90 = 1/2 mg/L) followed by ceftazidime/avibactam (94.2% susceptible, MIC50/90 = 2/8 mg/L). Up to 252 (17.3%) of the isolates were XDR. Carbapenemases/ESBLs were detected in 3.1% of the isolates, including VIM, IMP, GES, PER and OXA enzymes. The most frequent clone among the XDR isolates was ST175 (40.9%), followed by CC235 (10.7%), ST308 (5.2%) and CC111 (4.0%). Carbapenemase production varied geographically and involved diverse clones, including 16.5% of ST175 XDR isolates. Additionally, 56% of the sequenced XDR isolates showed horizontally acquired aminoglycoside-modifying enzymes, which correlated with tobramycin resistance. Two XDR isolates produced QnrVC1, but fluoroquinolone resistance was mostly caused by QRDR mutations. Beyond frequent mutations (>60%) in OprD and AmpC regulators, four isolates showed AmpC mutations associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam.

Conclusions

ST175 is the most frequent XDR high-risk clone in Spanish hospitals, but this nationwide survey also indicates a complex scenario in which major differences in local epidemiology, including carbapenemase production, need to be acknowledged in order to guide antimicrobial therapy.

Topic: phenotype – polymerase chain reaction – pseudomonas aeruginosa – mutation – colistin – epidemiology – ceftazidime – clone cells – drug resistance, microbial – electrophoresis, gel, pulsed-field – epidemiology, molecular – fluoroquinolones – spain – enzymes – tobramycin – aminoglycosides – antimicrobials – tazobactam – extended-spectrum beta lactamases – malnutrition-inflammation-cachexia syndrome – ceftolozane – avibactam

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; Pseudomonas aeruginosa; Spain; Colistin; Ceftazidime; Fluoroquinolones; Tobramycin; Aminoglycosides; Tazobactam; Avibactam.

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Evaluation of #apramycin against #spectinomycin-resistant and -susceptible strains of #Neisseria gonorrhoeae (J Antimicrob Chemother., abstract)

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

Evaluation of apramycin against spectinomycin-resistant and -susceptible strains of Neisseria gonorrhoeae

Stefan Riedel, Divya Vijayakumar, Gretchen Berg, Anthony D Kang, Kenneth P Smith, James E Kirby

Journal of Antimicrobial Chemotherapy, dkz012, https://doi.org/10.1093/jac/dkz012

Published: 27 January 2019

 

Abstract

Background

The emergence of Neisseria gonorrhoeae resistant to all currently available antimicrobial therapies poses a dire public health threat. New antimicrobial agents with activity against N. gonorrhoeae are urgently needed. Apramycin is an aminocyclitol aminoglycoside with broad-spectrum in vitro activity against MDR Gram-negative pathogens and Staphylococcus aureus. However, its activity against N. gonorrhoeae has not been described.

Objectives

The activity spectrum of apramycin against a collection of MDR N. gonorrhoeaewas assessed. Isolates tested included those susceptible and resistant to the structurally distinct aminocyclitol, spectinomycin.

Results

The modal MICs for apramycin and spectinomycin were 16 mg/L and 32 mg/L, respectively. The epidemiological cut-off (ECOFF) for apramycin was 64 mg/L. No strains among 77 tested had an MIC above this ECOFF, suggesting very low levels of acquired apramycin resistance. In time–kill analysis, apramycin demonstrated rapid bactericidal activity comparable to that of spectinomycin.

Conclusions

Apramycin has broad-spectrum, rapidly bactericidal activity against N. gonorrhoeae. Future pharmacokinetic and pharmacodynamic studies will be needed to determine whether apramycin and/or apramycin derivatives hold promise as new therapeutics for N. gonorrhoeae infection.

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; Neisseria gonorrhoeae; Spectinomycin; Apramycin; Aminoglycosides.

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