Characterization of #cefotaxime #resistant #urinary #Escherichia coli from primary care in South-West #England 2017–18 (J Antimicrob Chemother., abstract)

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

Characterization of cefotaxime-resistant urinary Escherichia coli from primary care in South-West England 2017–18

Jacqueline Findlay, Virginia C Gould, Paul North, Karen E Bowker, Martin O Williams, Alasdair P MacGowan, Matthew B Avison

Journal of Antimicrobial Chemotherapy, dkz397, https://doi.org/10.1093/jac/dkz397

Published: 20 September 2019

 

Abstract

Objectives

Third-generation cephalosporin-resistant Escherichia coli from community-acquired urinary tract infections are increasingly reported worldwide. We sought to determine and characterize the mechanisms of cefotaxime resistance employed by urinary E. coli obtained from primary care, over 12 months, in Bristol and surrounding counties in South-West England.

Methods

Cefalexin-resistant E. coli isolates were identified from GP-referred urine samples using disc susceptibility testing. Cefotaxime resistance was determined by subsequent plating onto MIC breakpoint plates. β-Lactamase genes were detected by PCR. WGS was performed on 225 isolates and analyses were performed using the Center for Genomic Epidemiology platform. Patient information provided by the referring general practices was reviewed.

Results

Cefalexin-resistant E. coli (n = 900) isolates were obtained from urines from 146 general practices. Following deduplication by patient approximately 69% (576/836) of isolates were cefotaxime resistant. WGS of 225 isolates identified that the most common cefotaxime-resistance mechanism was blaCTX-M carriage (185/225), followed by plasmid-mediated AmpCs (pAmpCs) (17/225), AmpC hyperproduction (13/225), ESBL blaSHV variants (6/225) or a combination of both blaCTX-M and pAmpC (4/225). Forty-four STs were identified, with ST131 representing 101/225 isolates, within which clade C2 was dominant (54/101). Ciprofloxacin resistance was observed in 128/225 (56.9%) of sequenced isolates, predominantly associated with fluoroquinolone-resistant clones ST131 and ST1193.

Conclusions

Most cefalexin-resistant E. coli isolates were cefotaxime resistant, predominantly caused by blaCTX-M carriage. The correlation between cefotaxime resistance and ciprofloxacin resistance was largely attributable to the high-risk pandemic clones ST131 and ST1193. Localized epidemiological data provide greater resolution than regional data and can be valuable for informing treatment choices in the primary care setting.

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; Cephalosporins; Fluoroquinolones; E. Coli; UTI; Cefalexin; Cefotaxime; UK; England.

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#Resistance to critically important #antimicrobials in #Australian silver #gulls (Chroicocephalus novaehollandiae) and evidence of #anthropogenic origins (J Antimicrob Chemother., abstract)

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

Resistance to critically important antimicrobials in Australian silver gulls (Chroicocephalus novaehollandiae) and evidence of anthropogenic origins

Shewli Mukerji, Marc Stegger, Alec Vincent Truswell, Tanya Laird, David Jordan, Rebecca Jane Abraham, Ali Harb, Mary Barton, Mark O’Dea, Sam Abraham

Journal of Antimicrobial Chemotherapy, dkz242, https://doi.org/10.1093/jac/dkz242

Published: 09 July 2019

 

Abstract

Objectives

Antimicrobial resistance (AMR) to critically important antimicrobials (CIAs) amongst Gram-negative bacteria can feasibly be transferred amongst wildlife, humans and domestic animals. This study investigated the ecology, epidemiology and origins of CIA-resistant Escherichia coli carried by Australian silver gulls (Chroicocephalus novaehollandiae), a gregarious avian wildlife species that is a common inhabitant of coastal areas with high levels of human contact.

Methods

Sampling locations were widely dispersed around the perimeter of the Australian continent, with sites separated by up to 3500 km. WGS was used to study the diversity and molecular characteristics of resistant isolates to ascertain their epidemiological origin.

Results

Investigation of 562 faecal samples revealed widespread occurrence of extended-spectrum cephalosporin-resistant (21.7%) and fluoroquinolone-resistant (23.8%) E. coli. Genome sequencing revealed that CIA-resistant E. coliisolates (n = 284) from gulls predominantly belonged to human-associated extra-intestinal pathogenic E. coli (ExPEC) clones, including ST131 (17%), ST10 (8%), ST1193 (6%), ST69 (5%) and ST38 (4%). Genomic analysis revealed that gulls carry pandemic ExPEC-ST131 clades (O25:H4 H30-R and H30-Rx) and globally emerging fluoroquinolone-resistant ST1193 identified among humans worldwide. Comparative analysis revealed that ST131 and ST1193 isolates from gulls overlapped extensively with human clinical isolates from Australia and overseas. The present study also detected single isolates of carbapenem-resistant E. coli (ST410-blaOXA-48) and colistin-resistant E. coli (ST345-mcr-1).

Conclusions

The carriage of diverse CIA-resistant E. coli clones that strongly resemble pathogenic clones from humans suggests that gulls can act as ecological sponges indiscriminately accumulating and disseminating CIA-resistant bacteria over vast distances.

Topic: colistin – epidemiology – animals, domestic – australia – aves – clone cells – disease transmission – drug resistance, microbial – ecology – feces – fluoroquinolones – genome – gram-negative bacteria – intestines – prescriptions, drug – surgical sponges – bacteria – silver – antimicrobials – escherichia coli – pandemics – genome sequencing – carbapenem resistance – extraintestinal pathogenic escherichia coli – 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; Carbapenem; Colistin; Fluoroquinolones; MCR1; E.Coli; Wild Birds; Australia.

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#Pandemic #fluoroquinolone #resistant #Escherichia coli clone #ST1193 emerged via simultaneous homologous #recombinations in 11 gene loci (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Pandemic fluoroquinolone resistant Escherichia coli clone ST1193 emerged via simultaneous homologous recombinations in 11 gene loci

Veronika Tchesnokova, Matthew Radey, Sujay Chattopadhyay, Lydia Larson, Jamie Lee Weaver, Dagmara Kisiela, and Evgeni V. Sokurenko

PNAS first published July 1, 2019 / DOI: https://doi.org/10.1073/pnas.1903002116

Edited by W. Ford Doolittle, Dalhousie University, Halifax, NS, Canada, and approved June 5, 2019 (received for review February 19, 2019)

 

Significance

Global growth in antibiotic resistance is a major social and health problem. The most common mechanism of high resistance to fluoroquinolones is the sequential acquisition of 3 mutations in 2 DNA topoisomerases, GyrA and ParC. We show that Escherichia coliST1193 acquired the mutant variants of gyrA and parC not by a conventional stepwise evolution but rather all at once. This was likely a result of a single transfer of about 1 Mb of chromosomal DNA from a phylogenetically distant donor E. coli strain, followed by 11 homologous recombination events involving the transferred DNA. Thus we describe a highly effective mechanism of acquisition of antimicrobial resistance by pathogenic bacteria, which led to the emergence of pandemic E. coli clone ST1193.

 

Abstract

Global growth in antibiotic resistance is a major social problem. A high level of resistance to fluoroquinolones requires the concurrent presence of at least 3 mutations in the target proteins—2 in DNA gyrase (GyrA) and 1 in topoisomerase IV (ParC), which occur in a stepwise manner. In the Escherichia coli chromosome, the gyrA and parC loci are positioned about 1 Mb away from each other. Here we show that the 3 fluoroquinolone resistance mutations are tightly associated genetically in naturally occurring strains. In the latest pandemic uropathogenic and multidrug-resistant E. coli clonal group ST1193, the mutant variants of gyrA and parC were acquired not by a typical gradual, stepwise evolution but all at once. This happened as part of 11 simultaneous homologous recombination events involving 2 phylogenetically distant strains of E. coli, from an uropathogenic clonal complex ST14 and fluoroquinolone-resistant ST10. The gene exchanges swapped regions between 0.5 and 139 Kb in length (183 Kb total) spread along 976 Kb of chromosomal DNA around and between gyrA and parC loci. As a result, all 3 fluoroquinolone resistance mutations in GyrA and ParC have simultaneously appeared in ST1193. Based on molecular clock estimates, this potentially happened as recently as <12 y ago. Thus, naturally occurring homologous recombination events between 2 strains can involve numerous chromosomal gene locations simultaneously, resulting in the transfer of distant but tightly associated genetic mutations and emergence of a both highly pathogenic and antibiotic-resistant strain with a rapid global spread capability.

Escherichia coli ST1193 – urinary tract infections – resistance to fluoroquinolones – homologous recombination – QRDR mutations

 

Footnotes

1 To whom correspondence may be addressed. Email: evs@uw.edu.

Author contributions: V.T. and E.V.S. designed research; V.T., M.R., S.C., L.L., J.L.W., and D.K. performed research; V.T., M.R., S.C., D.K., and E.V.S. analyzed data; and V.T., M.R., S.C., and E.V.S. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1903002116/-/DCSupplemental.

Published under the PNAS license.

Keywords: Antibiotics; Drugs Resistance; Fluoroquinolones; E. Coli; Recombination.

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#Trends and prediction of #antimicrobial susceptibility in #urinary #bacteria isolated in #European emergency departments: the #EuroUTI 2010-2016 Study (J Antimicrob Chemother., abstract)

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

Trends and prediction of antimicrobial susceptibility in urinary bacteria isolated in European emergency departments: the EuroUTI 2010-2016 Study

Alice Quaegebeur, Loïc Brunard, François Javaudin, Marie-Anne Vibet, Pascale Bemer, Quentin Le Bastard, Eric Batard, Emmanuel Montassier, EuroUTI 2010-2016 Study Group

Journal of Antimicrobial Chemotherapy, dkz274, https://doi.org/10.1093/jac/dkz274

Published: 30 June 2019

 

Abstract

Objectives

To assess recent trends in susceptibility to antibiotics among urinary isolates isolated in European emergency departments (EDs) and to identify isolates with a high (90% or more) predicted probability of susceptibility to fluoroquinolones or third-generation cephalosporins (3GCs).

Methods

In this cross-sectional study, we included urine cultures obtained from adult patients between 2010 and 2016 in 24 European EDs. Temporal trends were assessed using time-series analysis and multivariate logistic models. Multivariate logistic models were also used to predict susceptibility to fluoroquinolones or 3GCs from patient age and sex, year, month and ED.

Results

We included 88 242 isolates. Time-series analysis found a significant increase in susceptibility to fluoroquinolones and no significant trend for susceptibility to 3GCs. Adjusting for patient age and sex, ED and organism, multivariate models showed that susceptibility to 3GCs decreased from 2014 to 2016, while susceptibility to fluoroquinolones increased in 2015 and 2016. Among isolates from 2016, multivariate models predicted high probability of susceptibility to fluoroquinolones in 11% of isolates (positive predictive value 91%) and a high probability of susceptibility to 3GCs in 35% of isolates (positive predictive value 94%).

Conclusions

Susceptibility of ED urinary isolates to fluoroquinolones increased from 2014, while susceptibility to 3GCs decreased from 2015. Predictive models identified isolates with a high probability of susceptibility to fluoroquinolones or 3GCs. The ability of such models to guide the empirical treatment of pyelonephritis in the ED remains to be determined.

Topic: antibiotics – cephalosporins – adult – emergency service, hospital – fluoroquinolones – pyelonephritis – urinary tract – bacteria – urine culture – antimicrobial susceptibility

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; Fluoroquinolones; Cephalosporins; UTI; European Region.

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N-acetylcysteine blocks SOS induction and #mutagenesis produced by #fluoroquinolones in #Escherichia coli (J Antimicrob Chemother., abstract)

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

N-acetylcysteine blocks SOS induction and mutagenesis produced by fluoroquinolones in Escherichia coli

Ana I Rodríguez-Rosado, Estela Ynés Valencia, Alexandro Rodríguez-Rojas, Coloma Costas, Rodrigo S Galhardo, Jerónimo Rodríguez-Beltrán, Jesús Blázquez

Journal of Antimicrobial Chemotherapy, dkz210, https://doi.org/10.1093/jac/dkz210

Published: 18 May 2019

 

Abstract

Background

Fluoroquinolones such as ciprofloxacin induce the mutagenic SOS response and increase the levels of intracellular reactive oxygen species (ROS). Both the SOS response and ROS increase bacterial mutagenesis, fuelling the emergence of resistant mutants during antibiotic treatment. Recently, there has been growing interest in developing new drugs able to diminish the mutagenic effect of antibiotics by modulating ROS production and the SOS response.

Objectives

To test whether physiological concentrations of N-acetylcysteine, a clinically safe antioxidant drug currently used in human therapy, is able to reduce ROS production, SOS induction and mutagenesis in ciprofloxacin-treated bacteria without affecting antibiotic activity.

Methods

The Escherichia coli strain IBDS1 and its isogenic mutant deprived of SOS mutagenesis (TLS−) were treated with different concentrations of ciprofloxacin, N-acetylcysteine or both drugs in combination. Relevant parameters such as MICs, growth rates, ROS production, SOS induction, filamentation and antibiotic-induced mutation rates were evaluated.

Results

Treatment with N-acetylcysteine reduced intracellular ROS levels (by ∼40%), as well as SOS induction (by up to 75%) and bacterial filamentation caused by subinhibitory concentrations of ciprofloxacin, without affecting ciprofloxacin antibacterial activity. Remarkably, N-acetylcysteine completely abolished SOS-mediated mutagenesis.

Conclusions

Collectively, our data strongly support the notion that ROS are a key factor in antibiotic-induced SOS mutagenesis and open the possibility of using N-acetylcysteine in combination with antibiotic therapy to hinder the development of antibiotic resistance.

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; E. Coli; Ciprofloxacin; Fluoroquinolones; N-Acetylcysteine.

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Comparing #Antimicrobial Susceptibilities among #Mycoplasma pneumoniae Isolated from #Pediatric Patients in #Japan between Two Recent #Epidemic Periods (Antimicrob Agents Chemother., abstract)

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

Comparing Antimicrobial Susceptibilities among Mycoplasma pneumoniaeIsolated from Pediatric Patients in Japan between Two Recent Epidemic Periods

Tomohiro Oishi, Kento Takahashi, Shoko Wakabayashi, Yoshitaka Nakamura, Sahoko Ono, Mina Kono, Atsushi Kato, Aki Saito, Eisuke Kondo, Yuhei Tanaka, Hideto Teranishi, Hiroto Akaike,Takaaki Tanaka, Ippei Miyata, Satoko Ogita, Naoki Ohno, Takashi Nakano, Kazunobu Ouchi

DOI: 10.1128/AAC.02517-18

 

ABSTRACT

We compared the antimicrobial susceptibility of Mycoplasma pneumoniae isolated from pediatric patients in Japan in 2011–2012 and 2015–2016 when epidemics occurred. The antimicrobial activity of macrolides and tetracyclines against M. pneumoniae tended to be restored in 2015–2016. There was no change in the antimicrobial activity of quinolones against M. pneumoniae.

Copyright © 2019 Oishi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Antibiotics; Drugs Resistance; Quinolones; Macrolides; Tetracyclines; Mycoplasma pneumoniae; Japan.

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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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