#Phage #Therapy: A Renewed Approach to Combat #Antibiotic-Resistant #Bacteria (Cell Host Microbe, abstract)

[Source: Cell Host & Microbe, full page: (LINK). Abstract, edited.]

Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria

Kaitlyn E. Kortright, Benjamin K. Chan, Jonathan L. Koff, Paul E. Turner

DOI: https://doi.org/10.1016/j.chom.2019.01.014

 

Summary

Phage therapy, long overshadowed by chemical antibiotics, is garnering renewed interest in Western medicine. This stems from the rise in frequency of multi-drug-resistant bacterial infections in humans. There also have been recent case reports of phage therapy demonstrating clinical utility in resolving these otherwise intractable infections. Nevertheless, bacteria can readily evolve phage resistance too, making it crucial for modern phage therapy to develop strategies to capitalize on this inevitability. Here, we review the history of phage therapy research. We compare and contrast phage therapy and chemical antibiotics, highlighting their potential synergies when used in combination. We also examine the use of animal models, case studies, and results from clinical trials. Throughout, we explore how the modern scientific community works to improve the reliability and success of phage therapy in the clinic and discuss how to properly evaluate the potential for phage therapy to combat antibiotic-resistant bacteria.

Keywords: Antibiotics; Drugs Resistance; Bacteriophages.

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#Urgent action on #antimicrobial #resistance (Lancet Resp Med., summary)

[Source: The Lancet Respiratory Medicine, full page: (LINK). Summary, edited.]

Urgent action on antimicrobial resistance

Susan Rahimi

Published: February 12, 2019 / DOI: https://doi.org/10.1016/S2213-2600(19)30031-1

 

Summary

On Jan 24, 2019, the UK Government published their 20-year plan to curb and control antimicrobial resistance. The Secretary of State for Health and Social Care, Matt Hancock, announced the government’s three-pronged approach at the World Economic Forum at Davos, which will centre around prevention, innovation, and collaboration. Antimicrobial resistance is one of the biggest public health threats of the 21st century, and one that has the potential to reverse years of progress in human health and longevity. In 2016, the O’Neill review estimated that by 2050, 10 million lives a year could be lost due to antimicrobial resistance, exceeding the 8·2 million lives a year currently lost to cancer, and the cumulative economic loss to world economies might be as high as US$100 trillion. Antimicrobial resistance is a complex, global problem and action is urgently needed.

This article is available free of charge. Copyright © 2019 Elsevier Ltd. All rights reserved.

Keywords: Antibiotics; Drugs Resistance; Public Health; Global Health.

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#Eradication of persister cells of #Acinetobacter baumannii through combination of #colistin and #amikacin #antibiotics (J Antimicrob Chemother., abstract)

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

Eradication of persister cells of Acinetobacter baumannii through combination of colistin and amikacin antibiotics

Eun Seon Chung, Kwan Soo Ko

Journal of Antimicrobial Chemotherapy, dkz034, https://doi.org/10.1093/jac/dkz034

Published: 12 February 2019

 

Abstract

Objectives

Persister cells following antibiotic exposure may cause failure of antibiotic treatment. The synergistic effects of antibiotic combinations with respect to eliminating persister cells were investigated based on their characteristics.

Methods

For Acinetobacter baumannii clinical isolates, persister assays were performed using colistin, amikacin, imipenem and ciprofloxacin in various ways, including exposure to antibiotics in combination and sequentially. Persister phenotypes were observed through analysis of ATP concentration, membrane potential and transmission electron microscopy.

Results

Each A. baumannii isolate showed a specific survival rate of persister cells against each antibiotic. The persister cells were eradicated effectively by exposure to the combination of colistin and amikacin, especially in the sequential order of colistin then amikacin. While the persister cells were not identified after 6 h when exposed to the antibiotics in the order colistin then amikacin, they remained at 0.016% when antibiotic exposure was done in the order amikacin then colistin. Although membrane potential was low in both colistin and amikacin persisters, depletion of the intracellular ATP concentration was only observed in colistin persisters. In addition, transmission electron microscopy analysis showed that colistin persisters have a unique morphology with a rough and rippled membrane and many outer membrane vesicles. Empty pore-like structures surrounded by cracks were also observed.

Conclusions

In A. baumannii, the combination of colistin and amikacin was most effective for eradication of persister cells, probably due to different mechanisms of persister cell formation between antibiotics. It was also identified that the sequential order of colistin followed by amikacin was important to eradicate the persister cells.

Topic: antibiotics – amikacin – colistin – combined antibiotics – membrane potentials – acinetobacter baumannii – microscopes, transmission electron

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; Acinetobacter baumannii; Amikacin; Colistin.

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#Circulation of #plasmids harboring #resistance genes to #quinolones and/or extended spectrum #cephalosporins in multiple #Salmonella enterica serotypes from #swine in the #US (Antimicrob Agents Chemother., abstract)

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

Circulation of plasmids harboring resistance genes to quinolones and/or extended spectrum cephalosporins in multiple Salmonella enterica serotypes from swine in the United States

Ehud Elnekave, Samuel L. Hong, Seunghyun Lim, Shivdeep Singh Hayer, Dave Boxrud, Angela J. Taylor, Victoria Lappi, Noelle Noyes, Timothy J. Johnson, Albert Rovira, Peter Davies,Andres Perez, Julio Alvarez

DOI: 10.1128/AAC.02602-18

 

ABSTRACT

Nontyphoidal Salmonella enterica (NTS) poses a major public-health risk worldwide that is amplified by the existence of antimicrobial resistant strains, especially to quinolones and extended-spectrum cephalosporins (ESC). Little is known on the dissemination of plasmids harboring the acquired genetic determinants that confer resistance to these antimicrobials across NTS serotypes from livestock in the United States.

NTS isolates (n=183) from U.S. swine clinical cases retrieved during 2014-2016 were selected for sequencing based on their phenotypic resistance to enrofloxacin (quinolone) or ceftiofur (3rd-generation cephalosporin). De-novo assemblies were used to identify chromosomal mutations and acquired antimicrobial resistance genes (AARGs). In addition, plasmids harboring AARGs were identified using short-read assemblies and characterized using a multi-step approach that was validated by long-read sequencing.

AARGs to quinolones (qnrB15/qnrB19/qnrB2/qnrD/qnrS1/qnrS2/aac(6′)Ib-cr) and ESC (blaCMY-2/blaCTX-M-1/blaCTX-M-27/blaSHV-12) were distributed across serotypes, and were harbored by several plasmids. In addition, chromosomal mutations associated with resistance to quinolones were identified in the target enzyme and efflux pump regulation genes. The predominant plasmid harboring the prevalent qnrB19 gene was distributed across serotypes. It was identical to a plasmid previously reported in S. Anatum from swine in the U.S. (KY991369.1), and similar to Escherichia coli plasmids from humans in South America (GQ374157.1 and JN979787.1). Our findings suggest that plasmids harboring AARGs to critically important antimicrobials are present in multiple NTS serotypes circulating in swine in the U.S. and can contribute to resistance expansion through horizontal transmission.

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

Keywords: Antibiotics; Drugs Resistance; Cephalosporins; Quinolones; Pigs; USA.

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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

 

ABSTRACT

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.

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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

 

ABSTRACT

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.

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High #incidence of #MDR and #XDR #Pseudomonas aeruginosa isolates obtained from #patients with #ventilator-associated #pneumonia in #Greece, #Italy and #Spain as part of the MagicBullet clinical trial (J Antimicrob Chemother., abstract)

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

High incidence of MDR and XDR Pseudomonas aeruginosa isolates obtained from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial

Astrid Pérez, Eva Gato, José Pérez-Llarena, Felipe Fernández-Cuenca, María José Gude, Marina Oviaño, María Eugenia Pachón, José Garnacho, Verónica González, Álvaro Pascual, José Miguel Cisneros, Germán Bou

Journal of Antimicrobial Chemotherapy, dkz030, https://doi.org/10.1093/jac/dkz030

Published: 08 February 2019

 

Abstract

Objectives

To characterize the antimicrobial susceptibility, molecular epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa isolates recovered from respiratory tract samples from patients with ventilator-associated pneumonia enrolled in the MagicBullet clinical trial.

Methods

Isolates were collected from 53 patients from 12 hospitals in Spain, Italy and Greece. Susceptibility was determined using broth microdilution and Etest. MALDI-TOF MS was used to detect carbapenemase activity and carbapenemases were identified by PCR and sequencing. Molecular epidemiology was investigated using PFGE and MLST.

Results

Of the 53 isolates, 2 (3.8%) were considered pandrug resistant (PDR), 19 (35.8%) were XDR and 16 (30.2%) were MDR. Most (88.9%) of the isolates from Greece were MDR, XDR or PDR, whereas fewer of the isolates from Spain (33.3%) and Italy (43.5%) showed antibiotic resistance. Three Greek isolates were resistant to colistin. Overall, the rates of resistance of P. aeruginosa isolates to imipenem, ciprofloxacin, ceftolozane/tazobactam and ceftazidime/avibactam were 64.1%, 54.7%, 22.6% and 24.5%, respectively. All isolates resistant to ceftolozane/tazobactam and ceftazidime/avibactam (Greece, n = 10; and Italy, n = 2) carried blaVIM-2. Spanish isolates were susceptible to the new drug combinations. Forty-eight restriction patterns and 27 STs were documented. Sixty percent of isolates belonged to six STs, including the high-risk clones ST-111, ST-175 and ST-235.

Conclusions

MDR/XDR isolates were highly prevalent, particularly in Greece. The most effective antibiotic against P. aeruginosa was colistin, followed by ceftolozane/tazobactam and ceftazidime/avibactam. blaVIM-2 is associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam, and related to highly resistant phenotypes. ST-111 was the most frequent and disseminated clone and the clonal diversity was lower in XDR and PDR strains.

Topic: antibiotics – phenotype – polymerase chain reaction – pseudomonas aeruginosa – antibiotic resistance, bacterial – colistin – ciprofloxacin – ceftazidime – clone cells – drug combinations – electrophoresis, gel, pulsed-field – epidemiology, molecular – greece – ichthyosis, x-linked – imipenem – italy – respiratory system – sequence tagged sites – spain – spectrometry, mass, matrix-assisted laser desorption-ionization – sodium thiosulfate – antimicrobial susceptibility – tazobactam – ventilator-associated pneumonia – ceftolozane – avibactam – carbapenem 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; Pseudomonas aeruginosa; Pneumonia; Italy; Spain; Greece; Colistin; Ciprofloxacin; Ceftazidime; Iminpenem; Tazobactam; Ceftolozane; Avibactam.

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