Dynamics of #resistance #plasmids in #ESBL-producing #Enterobacteriaceae during post-infection #colonization (Antimicrob Agents Chemother., abstract)

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

Dynamics of resistance plasmids in extended spectrum β-lactamase-producing Enterobacteriaceae during post-infection colonization

Alma Brolund, Fredrika Rajer, Christian G Giske, Öjar Melefors, Emilia Titelman, Linus Sandegren

DOI: 10.1128/AAC.02201-18



Extended spectrum β-lactamase-producing Enterobacteriaceae (EPE) are a major cause of bloodstream infections and the colonization rate of EPE in the gut microbiota of individuals lacking prior hospitalization or comorbidities is increasing. In this study we performed an in-depth investigation of the temporal dynamics of EPE and their plasmids during one year by collecting fecal samples from three patients initially seeking medical care for urinary tract infections. In two of the patients the same strain that caused the UTI was found at all consecutive samplings from the gut microbiota and no other EPEs were detected, while in the third patient the UTI strain was only found in the initial UTI sample. Instead, this patient presented a complex situation where a mixed microbiota of different EPE strain types, including three different E. coli ST131 variants, as well as different bacterial species was identified over the course of the study. Different plasmid dynamics were displayed in each of the patients including spread of plasmids between different strain types over time, transposition of blaCTX-M-15 from the chromosome to a plasmid followed by subsequent loss through homologous recombination. Small cryptic plasmids were found in all isolates from all patients and they appear to move frequently between different strains in the microbiota. In conclusion, we could demonstrate an extensive variation of EPE strain types, plasmid composition, rearrangements and horizontal gene transfer of genetic material illustrating the high dynamics nature and interactive environment of the gut microbiota during post UTI carriage.

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

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; E. Coli; Enterobacteriaceae; Bacteremia.



Conjugal Transfer, #WGS, and #Plasmid Analysis of Four #mcr1–bearing Isolates from #US Patients (Antimicrob Agents Chemother., asbtract)

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

Conjugal Transfer, Whole Genome Sequencing, and Plasmid Analysis of Four mcr-1–bearing Isolates from U.S. Patients

Wenming Zhu, Adrian Lawsin, Rebecca L. Lindsey, Dhwani Batra, Kristen Knipe, Brian B. Yoo, K. Allison Perry, Lori A. Rowe, David Lonsway, Maroya S. Waters, J. Kamile Rasheed, Alison Laufer Halpin

DOI: 10.1128/AAC.02417-18



Four Enterobacteriaceae clinical isolates bearing mcr-1 gene-harboring plasmids were characterized. All isolates demonstrated the ability to transfer colistin resistance to E. coli;plasmids were stable in conjugants after multiple passages on non–selective media. mcr-1 was located on an IncX4 (n=3) or IncN (n=1) plasmid. The IncN plasmid harbored 13 additional antimicrobial resistance genes. Results indicate the mcr-1-bearing plasmids in this study are highly transferable in vitro and stable in the recipients.

This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Keywords: Antibiotics; Drugs Resistance; USA; E. Coli; Enterobacteriaceae; Colistin; MCR1.


Current #trends in the #treatment of #pneumonia due to #MDR #Gramnegative #bacteria (F1000Res., abstract)

[Source: F1000 Research, full page: (LINK). Abstract, edited.]

Current trends in the treatment of pneumonia due to multidrug-resistant Gram-negative bacteria [version 2; referees: 2 approved]

Richard R. Watkins1,2, David Van Duin3

Author details: 1 Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH, 44302, USA; 2 Department of Medicine, Northeast Ohio Medical University, Rootstown, OH, 44272, USA; 3 Department of Medicine, University of North Carolina, Chapel Hill, NC, 27514, USA



Pneumonia is one of the most common infections worldwide. Morbidity, mortality, and healthcare costs increase substantially when pneumonia is caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). The ongoing spread of antimicrobial resistance has made treating MDR-GNB pneumonia increasingly difficult. Fortunately, there have been some recent additions to our antibiotic armamentarium in the US and Europe for MDR-GNB, along with several agents that are in advanced stages of development. In this article, we review the risk factors for and current management of MDR-GNB pneumonia as well as novel agents with activity against these important and challenging pathogens.

Keywords: Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, antibiotics

Corresponding author: Richard R. Watkins

Competing interests: RRW serves on an advisory board and speakers’ bureau and has received research support from Allergan. DvD serves on advisory boards for Allergan, Achaogen, Shionogi, Tetraphase, Sanofi Pasteur, MedImmune, and Astellas and has received research funding from Steris Inc. and Scynexis.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright:  © 2019 Watkins RR and Van Duin D. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Watkins RR and Van Duin D. Current trends in the treatment of pneumonia due to multidrug-resistant Gram-negative bacteria [version 2; referees: 2 approved]. F1000Research 2019, 8(F1000 Faculty Rev):121 (https://doi.org/10.12688/f1000research.16517.2)

First published: 30 Jan 2019, 8(F1000 Faculty Rev):121 (https://doi.org/10.12688/f1000research.16517.1)

Latest published: 06 Feb 2019, 8(F1000 Faculty Rev):121 (https://doi.org/10.12688/f1000research.16517.2)

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; Pneumonia.


#Diarrheal #bacterial #pathogens and #MDR #enterobacteria in the Choqueyapu #River in La Paz, #Bolivia (PLoS One, abstract)

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


Diarrheal bacterial pathogens and multi-resistant enterobacteria in the Choqueyapu River in La Paz, Bolivia

Jessica Guzman-Otazo , Lucia Gonzales-Siles, Violeta Poma, Johan Bengtsson-Palme, Kaisa Thorell, Carl-Fredrik Flach, Volga Iñiguez, Åsa Sjöling

Published: January 14, 2019 / DOI: https://doi.org/10.1371/journal.pone.0210735



Water borne diarrheal pathogens might accumulate in river water and cause contamination of drinking and irrigation water. The La Paz River basin, including the Choqueyapu River, flows through La Paz city in Bolivia where it is receiving sewage, and residues from inhabitants, hospitals, and industry. Using quantitative real-time PCR (qPCR), we determined the quantity and occurrence of diarrheagenic Escherichia coli (DEC), Salmonella enterica, Klebsiella pneumoniae, Shigella spp. and total enterobacteria in river water, downstream agricultural soil, and irrigated crops, during one year of sampling. The most abundant and frequently detected genes were gapA and eltB, indicating presence of enterobacteria and enterotoxigenic E. coli(ETEC) carrying the heat labile toxin, respectively. Pathogen levels in the samples were significantly positively associated with high water conductivity and low water temperature. In addition, a set of bacterial isolates from water, soil and crops were analyzed by PCR for presence of the genes blaCTX-M, blaKPC, blaNDM, blaVIM and blaOXA-48. Four isolates were found to be positive for blaCTX-M genes and whole genome sequencing identified them as E. coli and one Enterobacter cloacae. The E. coli isolates belonged to the emerging, globally disseminated, multi-resistant E. coli lineages ST648, ST410 and ST162. The results indicate not only a high potential risk of transmission of diarrheal diseases by the consumption of contaminated water and vegetables but also the possibility of antibiotic resistance transfer from the environment to the community.


Citation: Guzman-Otazo J, Gonzales-Siles L, Poma V, Bengtsson-Palme J, Thorell K, Flach C-F, et al. (2019) Diarrheal bacterial pathogens and multi-resistant enterobacteria in the Choqueyapu River in La Paz, Bolivia. PLoS ONE 14(1): e0210735. https://doi.org/10.1371/journal.pone.0210735

Editor: Jesse Goodman, Georgetown University, UNITED STATES

Received: July 12, 2018; Accepted: December 31, 2018; Published: January 14, 2019

Copyright: © 2019 Guzman-Otazo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Data from this study are available at genbank under the BioProject number PRJNA449816 and BioSample accessions numbers SAMN08918384, SAMN08918385, SAMN08918386, SAMN08918387.

Funding: This work was supported by the Swedish International Development Cooperation Agency (Sida) to [VI and ÅS], and a Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS)/Swedish Water funded project on Risk-Based Decision Support for Safe Drinking Water [SWWA 13-102] to [ÅS]. The project is part of a Sweden-Bolivia Sida- Universidad Mayor de San Andres (UMSA) development program. JG-O acknowledges the financial support from the International Science Program (ISP). JB-P acknowledges financial support from FORMAS. The findings and conclusions contained in the article are those of the authors and do not necessarily reflect positions or policies of funder institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; Environmental Pollution; Bolivia.


Activity of #nacubactam (RG6080/OP0595) combinations against #MBL-producing #Enterobacteriaceae (J Antimicrob Chemother., abstract)

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

Activity of nacubactam (RG6080/OP0595) combinations against MBL-producing Enterobacteriaceae

Shazad Mushtaq, Anna Vickers, Neil Woodford, Andreas Haldimann, David M Livermore

Journal of Antimicrobial Chemotherapy, dky522, https://doi.org/10.1093/jac/dky522

Published: 24 December 2018




Diazabicyclooctanes (DBOs) are promising β-lactamase inhibitors. Some, including nacubactam (OP0595/RG6080), also bind PBP2 and have an enhancer effect, allowing activity against Enterobacteriaceae with MBLs, which DBOs do not inhibit. We tested the activity of nacubactam/β-lactam combinations against MBL-producing Enterobacteriaceae.


Test panels comprised (i) 210 consecutive Enterobacteriaceae with NDM or VIM MBLs, as referred by UK diagnostic laboratories, and (ii) 99 supplementary MBL-producing Enterobacteriaceae, representing less prevalent phenotypes, species and enzymes. MICs were determined by CLSI agar dilution.


MICs of nacubactam alone were bimodal, clustering at 1–8 mg/L or >32 mg/L; >85% of values for Escherichia coli and Enterobacter spp. fell into the low MIC cluster, whereas Proteeae were universally resistant and the Klebsiella spp. were divided between the two groups. Depending on the prospective breakpoint (4 + 4 or 8 + 4 mg/L), and on whether all isolates were considered or solely the Consecutive Collection, meropenem/nacubactam and cefepime/nacubactam inhibited 80.3%–93.3% of MBL producers, with substantial gains over nacubactam alone. Against the most resistant isolates (comprising 57 organisms with MICs of nacubactam >32 mg/L, cefepime ≥128 mg/L and meropenem ≥128 mg/L), cefepime/nacubactam at 8 + 4 mg/L inhibited 63.2% and meropenem/nacubactam at 8 + 4 mg/L inhibited 43.9%. Aztreonam/nacubactam, incorporating an MBL-stable β-lactam partner, was almost universally active against the MBL producers and, unlike aztreonam/avibactam, had an enhancer effect.


Nacubactam combinations, including those using MBL-labile β-lactams, e.g. meropenem and cefepime, can overcome most MBL-mediated resistance. This behaviour reflects nacubactam’s direct antibacterial and enhancer activity.

Topic: phenotype – cefepime – agar – aztreonam – enterobacter – enterobacteriaceae – klebsiella – laboratory – lactams – diagnosis – enzymes – meropenem – anti-bacterial agents – escherichia coli – enhancer of transcription – dilution technique – dilute (action) – binding (molecular function) – malnutrition-inflammation-cachexia syndrome – avibactam


© 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: Antibiotics; Drugs Resistance; Enterobacteriaceae; Aztreonam; Meropenem; Nacubactam.


Inhibiting #antibiotic resistant #Enterobacteriaceae by #microbiota-mediated intracellular acidification (J Exp Med., abstract)

[Source: Journal of Experimental Medicine, full page: (LINK). Abstract, edited.]

Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification

Matthew T. Sorbara , Krista Dubin, Eric R. Littmann, Thomas U. Moody,  Emily Fontana,  Ruth Seok, Ingrid M. Leiner, Ying Taur, Jonathan U. Peled, Marcel R.M. van den Brink, Yael Litvak, Andreas J. Bäumler, Jean-Luc Chaubard, Amanda J. Pickard, Justin R. Cross, Eric G. Pamer

DOI: 10.1084/jem.20181639 | Published December 18, 2018



Klebsiella pneumoniae, Escherichia coli, and other members of the Enterobacteriaceae family are common human pathogens that have acquired broad antibiotic resistance, rendering infection by some strains virtually untreatable. Enterobacteriaceae are intestinal residents, but generally represent <1% of the adult colonic microbiota. Antibiotic-mediated destruction of the microbiota enables Enterobacteriaceae to expand to high densities in the colon, markedly increasing the risk of bloodstream invasion, sepsis, and death. Here, we demonstrate that an antibiotic-naive microbiota suppresses growth of antibiotic-resistant clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis by acidifying the proximal colon and triggering short chain fatty acid (SCFA)–mediated intracellular acidification. High concentrations of SCFAs and the acidic environment counter the competitive edge that O2 and NO3 respiration confer upon Enterobacteriaceae during expansion. Reestablishment of a microbiota that produces SCFAs enhances clearance of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis from the intestinal lumen and represents a potential therapeutic approach to enhance clearance of antibiotic-resistant pathogens.

Submitted: 24 August 2018 – Revision received 26 October 2018 – Accepted: 7 December 2018

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae.


Diverse #vectors and mechanisms #spread #NDM beta-lactamases among #carbapenem resistant #Enterobacteriaceae in the Greater #Boston area (Antimicrob Agents Chemother., abstract)

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

Diverse vectors and mechanisms spread NDM beta-lactamases among carbapenem resistant Enterobacteriaceae in the Greater Boston area

Nicole Pecora, Xiaomin Zhao, Kathleen Nudel, Maria Hoffmann, Ning Li, Andrew B. Onderdonk, Deborah Yokoe, Eric Brown, Marc Allard, Lynn Bry

DOI: 10.1128/AAC.02040-18



New Delhi metallo-beta-lactamases (NDMs) are an uncommon but emerging cause of carbapenem resistance in the United States. Genomic factors promoting their domestic spread remain poorly characterized. A prospective genomic surveillance program among Boston-area hospitals identified multiple new occurrences of NDM carrying strains of E. coli and E. cloacaecomplex in inpatient and outpatient settings, representing the first occurrences of NDM-mediated resistance since initiating genomic surveillance in 2011. Cases included domestic patients with no international exposures. PacBio sequencing of isolates identified strain characteristics, resistance genes, and the complement of mobile vectors mediating spread. Analyses revealed a common 3114-bp region containing the blaNDM gene, with carriage of this conserved region among unique strains by diverse transposon and plasmid backbones. Functional studies revealed broad capacity for blaNDM transmission by conjugation, transposition, and complex inter-plasmid recombination events. NDMs represent a rapidly spreading form of drug resistance that can occur in inpatient and outpatient settings and in patients without international exposures. In contrast to Tn4401-based spread of Klebsiella pneumoniae carbapenemases (KPCs), diverse transposable elements mobilize NDM enzymes, commonly with other resistance genes, enabling naïve strains to acquire multi- and extensively-drug resistance profiles with single transposition or plasmid conjugation events. Genomic surveillance provides effective means to rapidly identify these gene-level drivers of resistance and mobilization, to inform clinical decisions to prevent further spread.

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

Keywords: Antibiotics; Drugs Resistance; Carbapenem; NDM1; USA; Enterobacteriaceae.