Acquisition and Loss of #CTX-M-Producing and Non-Producing #Escherichia coli in the Fecal #Microbiome of #Travelers to South #Asia (mBio, abstract)

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

Acquisition and Loss of CTX-M-Producing and Non-Producing Escherichia coli in the Fecal Microbiome of Travelers to South Asia

Edward R. Bevan, Alan McNally, Christopher M. Thomas, Laura J. V. Piddock, Peter M. Hawkey

George A. Jacoby, Editor

DOI: 10.1128/mBio.02408-18

 

ABSTRACT

Over 80% of travelers from the United Kingdom to the Indian subcontinent acquire CTX-M-producing Escherichia coli (CTX-M-EC), but the mechanism of CTX-M-EC acquisition is poorly understood. We aimed to investigate the dynamics of CTX-M-EC acquisition in healthy travelers and how this relates to populations of non-CTX-M-EC in the fecal microbiome. This is a prospective observational study of healthy volunteers traveling from the United Kingdom to South Asia. Fecal samples were collected pre- and post-travel at several time points up to 12 months post-travel. A toothpicking experiment was used to determine the proportion of cephalosporin-sensitive E. coli in fecal samples containing CTX-M-EC. MLST and SNP type of pre-travel and post-travel E. coli were deduced by WGS. CTX-M-EC was acquired by 89% (16/18) of volunteers. Polyclonal acquisition of CTX-M-EC was seen in 8/15 volunteers (all had >3 STs across post-travel samples), suggesting multiple acquisition events. Indistinguishable CTX-M-EC clones (zero SNPs apart) are detectable in serial fecal samples up to 7 months after travel, indicating stable maintenance in the fecal microbiome on return to the United Kingdom in the absence of selective pressure. CTX-M-EC-containing samples were often co-colonized with novel, non-CTX-M strains after travel, indicating that acquisition of non-CTX-M-EC occurs alongside CTX-M-EC. The same pre-travel non-CTX-M strains (<10 SNPs apart) were found in post-travel fecal samples after CTX-M-EC had been lost, suggesting return of the fecal microbiome to the pre-travel state and long-term persistence of minority strains in travelers who acquire CTX-M-EC.

 

IMPORTANCE

Escherichia coli strains which produce CTX-M extended-spectrum beta-lactamases are endemic as colonizers of humans and in the environment in South Asia. This study demonstrates that acquisition of CTX-M-producing E. coli (CTX-M-EC) in travelers from the United Kingdom to South Asia is polyclonal, which is likely due to multiple acquisition events from contaminated food and drinking water during travel. CTX-M-EC frequently persists in the fecal microbiome for at least 1 year after acquisition, often alongside newly acquired non-CTX-M E. coli strains. In travelers who acquire CTX-M-EC, pre-travel non-CTX-M E. coli remains as a minority population in the gut until the CTX-M-EC strains are lost. The non-CTX-M strains are then reestablished as the predominant E. coli population. This study has shed light on the dynamics of CTX-M-EC acquisition, colonization, and loss after travel. Future work involving manipulation of nonvirulent resident E. coli could be used to prevent colonization with antibiotic-resistant E. coli.

Keywords: Antibiotics; Drugs Resistance; Cephalosporins; E. Coli; UK; Asian region.

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Emergence of #resistance to #quinolones and #betalactam #antibiotics in enteroaggregative and enterotoxigenic #Ecoli causing #traveler’s #diarrhea (Antimicrob Agents Chemother., abstract)

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

Emergence of resistance to quinolones and β–lactam antibiotics in enteroaggregative and enterotoxigenic Escherichia coli causing traveler’s diarrhea.

Elisabet Guiral, Milene Gonçalves Quiles, Laura Muñoz, Javier Moreno-Morales, Izaskun Alejo-Cancho, Pilar Salvador, Miriam J. Alvarez-Martinez, Francesc Marco, Jordi Vila

DOI: 10.1128/AAC.01745-18

 

ABSTRACT

The objective of this study was to assess the antimicrobial resistance of enteroaggregative Escherichia coli (EAEC) and enterotoxigenic E. coli (ETEC) causing traveler’s diarrhea (TD) and investigate the molecular characterization of antimicrobial resistance genes to third generation cephalosporins, chepamycins and quinolones. Overall, 39 EAEC and 43 ETEC clinical isolates were studied. The susceptibility of EAEC and ETEC against ampicillin, amoxicillin-clavulanic acid, cefotaxime, imipenem, chloramphenicol, tetracycline, cotrimoxazole, nalidixic acid, ciprofloxacin, azithromycin and rifaximin was determined. All genes encoding resistant determinants were detected by PCR or PCR and DNA sequencing. The epidemiology of selected EAEC and ETEC strains was studied using MLST. The resistance to quinolones of EAEC and ETEC strains causing TD has significantly increased over the last decades, and high percentages has been found especially in patients traveling to India and sub-Saharan Africa. The ST38 and ST131 carrying the blaCTX-M-15 and blaCTX-M-27 genes, respectively, are highly prevalent among ESBL-producing EAEC and ETEC. The cephamycinase ACT-20 is described in the present study for the first time in EAEC and ETEC strains causing TD in patients who had traveled to Central America. The percentages of resistance to azithromycin in EAEC and ETEC isolates from patients to South-East Asia/India and Africa are above 25%. Meanwhile, rifaximin is still active against EAEC and ETEC with the prevalence of resistant strains not being high. In conclusion, fluoroquinolones should no longer be considered the drugs of choice for the prevention or treatment in TD for travelers traveling to India and Africa. Azithromycin and rifaximin are still a good alternative to treat TD caused by EAEC or ETEC.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; Quinolones; Azithromycin; Rifaximin.

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#Phylogenomic analysis of extraintestinal pathogenic #Ecoli ST1193, an emerging #MDR clonal group (Antimicrob Agents Chemother., abstract)

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

Phylogenomic analysis of extraintestinal pathogenic Escherichia coli ST1193, an emerging multidrug-resistant clonal group

Timothy J. Johnson, Ehud Elnekave, Elizabeth A. Miller, Jeannette Munoz-Aguayo, Cristian Flores Figueroa, Brian Johnston, Daniel W. Nielson, Catherine M. Logue, James R. Johnson

DOI: 10.1128/AAC.01913-18

 

ABSTRACT

The fluoroquinolone-resistant ST1193 clonal group of Escherichia coli, from the ST14 clonal complex (STc14) within phylogenetic group B2, has appeared recently as an important cause of extraintestinal disease in humans. Although this emerging lineage has been characterized to some extent using conventional methods, it has not been studied extensively at the genomic level. Here, we used whole genome sequence analysis to compare 355 ST1193 isolates with 72 isolates from other STs within STc14. Using core genome phylogeny, the ST1193 isolates formed a tightly clustered clade with many genotypic similarities, as compared to ST14 isolates. All ST1193 isolates possessed the same set of three chromosomal mutations conferring fluoroquinolone resistance, carried the fimH64 allele, and were lactose non-fermenting. Analysis revealed an evolutionary progression from K1 to K5 capsular types and acquisition of an F-type virulence plasmid followed by changes in plasmid structure congruent with genome phylogeny. In contrast, the numerous identified antimicrobial resistance genes were distributed incongruently with the underlying phylogeny, suggesting frequent gain or loss of the corresponding resistance gene cassettes despite retention of the presumed carrier plasmids. Pangenome analysis revealed gains and losses of genetic loci occurring during the transition from ST14 to ST1193, and from the K1 to K5 capsular types. Using time-scaled phylogenetic analysis, we estimated that current ST1193 clades first emerged approximately 25 years ago. Overall, ST1193 appears to be a recently emerged clone in which both stepwise and mosaic evolution likely have contributed to epidemiologic success.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

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

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Novel partners with #colistin to increase its in vivo therapeutic effectiveness and prevent the occurrence of colistin #resistance in #NDM- and #MCR-co-producing #Ecoli in a murine infection model (J Antimicrob Chemother., abstract)

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

Novel partners with colistin to increase its in vivotherapeutic effectiveness and prevent the occurrence of colistin resistance in NDM- and MCR-co-producing Escherichia coli in a murine infection model

Yang Yu, Timothy R Walsh, Run-Shi Yang, Mei Zheng, Meng-Chao Wei, Jonathan M Tyrrell, Yang Wang, Xiao-Ping Liao, Jian Sun, Ya-Hong Liu

Journal of Antimicrobial Chemotherapy, dky413, https://doi.org/10.1093/jac/dky413

Published: 20 October 2018

 

Abstract

Objectives

The emergence of NDM- and MCR-1-co-producing Escherichia coli has compromised the use of carbapenems and colistin, which are critically important in clinical therapy, and represents a severe threat to public health worldwide. Here, we demonstrate synergism of colistin combined with existing antibiotics as a potential strategy to overcome XDR E. coli co-harbouring NDM and MCR-1 genes.

Methods

To comprehensively evaluate their combined activity, antibiotic combinations were tested against 34 different E. coli strains carrying both NDM and MCR-1 genes. Antibiotic resistance profiles and molecular characteristics were investigated by susceptibility testing, PCR, MLST, S1-PFGE and WGS. Antibiotic synergistic efficacy was evaluated through in vitro chequerboard experiments and dose–response assays. A mouse model was used to confirm active combination therapies. Additionally, combinations were tested for their ability to prevent high-level colistin-resistant mutants (HLCRMs).

Results

Combinations of colistin with rifampicin, rifabutin and minocycline showed synergistic activity against 34 XDR NDM- and MCR-1-co-producing E. coli strains, restoring, in part, susceptibility to both colistin and the partnering antibiotics. The therapeutic effectiveness of colistin combined with rifampicin or minocycline was demonstrated in a mouse model. Furthermore, colistin plus rifampicin showed significant activity in preventing the occurrence of HLCRMs.

Conclusions

The synergism of colistin in combinations with rifampicin, rifabutin or minocycline offers viable therapeutic alternatives against XDR NDM- and MCR-positive E. coli.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2018. 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: Research; Abstracts; Antibiotics; Drugs Resistance; Colistin; E. Coli; Rifampicin; Rifabutin; Minocycline; MCR; NDM.

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#Morbidity and #mortality due to #shigella and enterotoxigenic #Ecoli diarrhoea: the Global Burden of Disease Study 1990–2016 (Lancet Infect Dis., abstract)

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

Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990–2016

Ibrahim A Khalil, Christopher Troeger, Brigette F Blacker, Puja C Rao, Alexandria Brown, Deborah E Atherly, Thomas G Brewer, Cyril M Engmann, Eric R Houpt, Gagandeep Kang, Karen L Kotloff, Myron M Levine, Stephen P Luby, Calman A MacLennan, William K Pan, Patricia B Pavlinac, James A Platts-Mills, Firdausi Qadri, Mark S Riddle, Edward T Ryan, David A Shoultz, A Duncan Steele, Judd L Walson, John W Sanders, Ali H Mokdad, Christopher J L Murray, Simon I Hay, Robert C Reiner Jr

Lancet Infect Dis 2018 / Published Online September 25, 2018 / DOI: http://dx.doi.org/10.1016/S1473-3099(18)30475-4

 

Summary

Background

Shigella and enterotoxigenic Escherichia coli (ETEC) are bacterial pathogens that are frequently associated with diarrhoeal disease, and are a significant cause of mortality and morbidity worldwide. The Global Burden of Diseases, Injuries, and Risk Factors study 2016 (GBD 2016) is a systematic, scientific effort to quantify the morbidity and mortality due to over 300 causes of death and disability. We aimed to analyse the global burden of shigella and ETEC diarrhoea according to age, sex, geography, and year from 1990 to 2016.

Methods

We modelled shigella and ETEC-related mortality using a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We used a compartmental meta-regression tool to model the incidence of shigella and ETEC, which enforces an association between incidence, prevalence, and remission on the basis of scientific literature, population representative surveys, and health-care data. We calculated 95% uncertainty intervals (UIs) for the point estimates.

Findings

Shigella was the second leading cause of diarrhoeal mortality in 2016 among all ages, accounting for 212438 deaths (95% UI 136979–326 913) and about 13·2% (9·2–17·4) of all diarrhoea deaths. Shigella was responsible for 63 713 deaths (41 191–93 611) among children younger than 5 years and was frequently associated with diarrhoea across all adult age groups, increasing in elderly people, with broad geographical distribution. ETEC was the eighth leading cause of diarrhoea mortality in 2016 among all age groups, accounting for 51 186 deaths (26 757–83064) and about 3·2% (1·8–4·7) of diarrhoea deaths. ETEC was responsible for about 4·2% (2·2–6·8) of diarrhoea deaths in children younger than 5 years.

Interpretation

The health burden of bacterial diarrhoeal pathogens is difficult to estimate. Despite existing prevention and treatment options, they remain a major cause of morbidity and mortality globally. Additional emphasis by public health officials is needed on a reduction in disease due to shigella and ETEC to reduce disease burden.

Funding Bill & Melinda Gates Foundation.

Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

Keywords: Shigella spp.; E. Coli; ETEC; Worldwide.

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A large, #refractory #nosocomial #outbreak of #KPC-producing #Ecoli demonstrates carbapenemase gene #outbreaks involving #sink sites require novel approaches to infection control (AAC, abstract)

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

A large, refractory nosocomial outbreak of Klebsiella pneumoniaecarbapenemase (KPC)-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control

V Decraene, H. T. T. Phan, R George, D. H. Wyllie, O Akinremi, Z Aiken, P Cleary, A Dodgson, L Pankhurst, D. W. Crook, C Lenney, A. S. Walker, N Woodford, R Sebra, F Fath-Ordoubadi,A. J. Mathers, A. C. Seale, M Guiver, A McEwan, V Watts, W Welfare, N Stoesser, J Cawthorne, the TRACE Investigators’ Group

DOI: 10.1128/AAC.01689-18

 

ABSTRACT

Carbapenem-resistant Enterobacteriaceae (CRE) are a health threat, but effective control interventions remain unclear. Hospital wastewater sites are increasingly highlighted as important potential reservoirs. We investigated a large Klebsiella pneumoniae carbapenemase (KPC)-producing E. coli (KPC-EC) outbreak and wider CRE incidence trends over eight years in the Central Manchester Foundation NHS Trust (CMFT), UK, to determine the impact of Infection Prevention and Control measures.

Bacteriology and patient administration data (2009 to 2017) were linked; a subset of CMFT/regional KPC-EC isolates (n=268) was sequenced. Control interventions followed international guidelines and included cohorting, rectal screening (n=184,539 screens), environmental sampling, enhanced cleaning, and ward closure/plumbing replacement. Segmented regression of time trends of CRE detections was used to evaluate the impact of interventions on CRE incidence.

Genomic analysis (n=268 isolates) identified spread of a KPC-EC outbreak clone (ST216, strain-A; n=125) amongst patients and the environment, particularly on two cardiac wards (W3/W4), despite control measures. ST216 strain-A had caused an antecedent outbreak, and shared its KPC plasmids with other E. coli lineages and Enterobacteriaceae. CRE acquisition incidence declined after W3/W4 closure and plumbing replacement, suggesting an environmental contribution. However, W3/W4 wastewater sites were rapidly re-colonised with CRE and patient CRE acquisitions recurred, albeit at lower rates.

Patient relocation and plumbing replacement were associated with control of a clonal KPC-EC outbreak; however, environmental contamination with CRE and patient CRE acquisitions recurred rapidly following this intervention. The large numbers of cases and persistence of blaKPC in E. coli, including pathogenic lineages, is a concern.

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Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; UK; England; E. Coli; Carbapenem; Nosocomial Outbreaks.

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#Synergistic antimicrobial #activity of #colistin in combination with #rifampin and #azithromycin against #Escherichia coli producing #MCR-1 (Antimicrob Agents Chemother., abstract)

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

Synergistic antimicrobial activity of colistin in combination with rifampin and azithromycin against Escherichia coli producing MCR-1

Yanqin Li, Xiaohuan Lin, Xuan Yao, Yan Huang, Wenguang Liu, Tao Ma, Binghu Fang

DOI: 10.1128/AAC.01631-18

 

ABSTRACT

The lack of available antibiotics is a global public health problem due to the emergence of antimicrobial resistance. Effective therapeutic regimens are urgently needed against Escherichia coli that produces colistin-resistance gene mcr-1 and to inhibit the emergence of resistance. In this study, we assessed the antimicrobial activity of a series of concentrations of colistin-based combinations with rifampin and/or azithromycin against three strains of Escherichia coli, including colistin-resistant isolate MZ1501R, HE1704R that produces MCR-1, and colistin-susceptible isolate MZ1509S. Experiments were conducted at a medium inoculum of ∼107 CFU/mL over 48 h. Subsequently, the in vivo therapeutic effect was investigated using a neutropenic thigh-infected mouse model. Almost all monotherapies showed unsatisfactory antibacterial activity against E. coli isolates producing MCR-1. By contrast, colistin in combination with rifampin or azithromycin resulted in an obvious decrease in bacterial burden, albeit with regrowth. More obviously, synergistic antimicrobial activity of colistin-based triple combination therapy with rifampin and azithromycin was observed, resulting in a rapid and exhaustive antibacterial effect. In vivo treatments confirmed these findings where a mean decrease of 0.38 to 0.90 log10 CFU and 1.27 to 1.78 log10 CFU was noted after 24 h and 48 h of treatment, respectively, against colistin-resistant E. coli strains when 5 mg/kg colistin was combined with rifampin and azithromycin. Colistin-based combinations with rifampin and azithromycin provide a more active therapeutic regimen than monotherapy or colistin-based double combinations against E. coli producing MCR-1.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Colistin; E. Coli; MCR1; Azithromycin; Rifampin; Animal models.

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