#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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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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Updated #Prevalence of #mcr-like Genes among #Escherichia coli and #Klebsiella pneumoniae in SENTRY Program and Characterization of mcr-1.11 Variant (Antimicrob Agents Chemother., abstract)

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

Updated Prevalence of mcr-like Genes among Escherichia coli and Klebsiella pneumoniae in SENTRY Program and Characterization of mcr-1.11 Variant

Lalitagauri M. Deshpande, Cory Hubler, Andrew P. Davis, Mariana Castanheira

DOI: 10.1128/AAC.02450-18

 

ABSTRACT

Increased prevalence of infections caused by Gram-negative pathogens that are multidrug resistant has prompted the reconsideration of polymyxins as therapeutic options.…

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

Keywords: Antibiotics; Drugs Resistance; Polymyxins; MCR1.

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The #antimicrobial #resistome in relation to antimicrobial use and #biosecurity in #pig #farming, a metagenome-wide association study in nine #European countries (J Antimicrob Chemother., abstract)

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

The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries

Liese Van Gompel, Roosmarijn E C Luiken, Steven Sarrazin, Patrick Munk, Berith E Knudsen, Rasmus B Hansen, Alex Bossers, Frank M Aarestrup, Jeroen Dewulf, Jaap A Wagenaar, Dik J Mevius, Heike Schmitt, Dick J J Heederik, Alejandro Dorado-García, Lidwien A M Smit, EFFORT consortium

Journal of Antimicrobial Chemotherapy, dky518, https://doi.org/10.1093/jac/dky518

Published: 14 January 2019

 

Abstract

Objectives

Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe.

Methods

A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM).

Results

Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models.

Conclusions

Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions.

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; Macrolides; Colistin; Tetracyclines; Pigs; European Region.

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Detection of #mcr-mediated #colistin #resistance in #Escherichia coli isolated from #pigs in small-scale #farms in #Cambodia (Antimicrob Agents Chemother., abstract)

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

Detection of mcr-mediated colistin resistance in Escherichia coli isolated from pigs in small-scale farms in Cambodia

G Ström Hallenberg, S Börjesson, S Sokerya, T Sothyra, U Magnusson

DOI: 10.1128/AAC.02241-18

 

ABSTRACT

Colistin is today considered a last-line antimicrobial for the treatment of infections in humans caused by multidrug-resistant Enterobacteriaceae [1]. The dissemination of colistin resistance has received increased attention since a mobilized gene conferring resistance to colistin, mcr-1, was described in Enterobacteriaceae from humans and food-producing animals in China in 2015 [2], and additional gene homologs have since been identified [3-15].

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

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1; Pigs; Cambodia.

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Dose-dependent Synergistic Interactions of #Colistin with #Rifampicin, #Meropenem and #Tigecycline against #Carbapenem-resistant #Klebsiella pneumoniae #Biofilms (Antimicrob Agents Chemother., abstract)

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

Dose-dependent Synergistic Interactions of Colistin with Rifampicin, Meropenem and Tigecycline against Carbapenem-resistant Klebsiella pneumoniae Biofilms

Anastasia Geladari, Maria Simitsopoulou, Charalampos Antachopoulos, Emmanuel Roilides

DOI: 10.1128/AAC.02357-18

 

ABSTRACT

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) can cause biofilm-related bloodstream infections associated with significant morbidity and mortality worldwide. We investigated the bactericidal activities of colistin (CST), rifampicin (RIF), meropenem (MEM), gentamicin (GEN) and tigecycline (TGC) alone and that of CST in combination with RIF, MEM, GEN or TGC against CR-Kp mature biofilms. Twenty CR-Kp blood isolates were derived from equal number of bloodstream infections in adult patients. Biofilm formation was assessed by staining with 0.4% crystal violet and measuring optical density spectrophotometrically at 545 nm. Biofilm damage was measured as % reduction of metabolic activity by XTT assay. MIC50 for biofilms was determined as the minimum concentration that caused ≥50% bacterial damage compared to that for untreated controls. Antibacterial drug interactions were analyzed by the Bliss independence model. Four of the twenty CR-Kp isolates were biofilm producers. Biofilm MIC50’s of CST, RIF, MEM, GEN and TGC for these isolates were 64, 8, >256, 128 and 8 mg/L, respectively. Synergistic interactions were observed at 32-64 mg/L of CST combined with 0.25-4 mg/L of RIF, at 32 mg/L of CST combined with 0.007-0.25 mg/L of MEM, and at 16-32 mg/L of CST combined with 16-64 mg/L of TGC. The synergy was highest for CST+RIF, with %ΔE±SE 49.87±9.22 compared to 29.52±4.97 for CST+MEM (p<0.001) and 32.44±6.49 for CST+TGC (p<0.001). Indifferent results were exhibited by CST+GEN. None of the combinations exhibited antagonism. These drug interactive findings, especially that of CST with RIF, may be of importance in the treatment of biofilm-related CR-Kp infections.

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

Keywords: Antibiotics; Drugs Resistance; Carbapene; Klebsiella pneumoniae; Colistin; Gentamicin; Tigecycline; Meropenem; Rifampicin.

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