Role of #Berberine in the #Treatment of #MRSA #Infections (Sci Rep., abstract)

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

Article | Open

Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

Ming Chu, Ming-bo Zhang, Yan-chen Liu, Jia-rui Kang, Zheng-yun Chu, Kai-lin Yin, Ling-yu Ding, Ran Ding, Rong-xin Xiao, Yi-nan Yin, Xiao-yan Liu & Yue-dan Wang

Scientific Reports 6, Article number: 24748 (2016) / doi:10.1038/srep24748

Received: 18 December 2015 – Accepted: 04 April 2016 – Published online: 22 April 2016

 

Abstract

Berberine is an isoquinoline alkaloid widely used in the treatment of microbial infections. Recent studies have shown that berberine can enhance the inhibitory efficacy of antibiotics against clinical multi-drug resistant isolates of methicillin-resistant Staphylococcus aureus (MRSA). However, the underlying mechanisms are poorly understood. Here, we demonstrated that sub-minimum inhibitory concentrations (MICs) of berberine exhibited no bactericidal activity against MRSA, but affected MRSA biofilm development in a dose dependent manner within the concentration ranging from 1 to 64 μg/mL. Further study indicated that berberine inhibited MRSA amyloid fibrils formation, which consist of phenol-soluble modulins (PSMs). Molecular dynamics simulation revealed that berberine could bind with the phenyl ring of Phe19 in PSMα2 through hydrophobic interaction. Collectively, berberine can inhibit MRSA biofilm formation via affecting PSMs’ aggregation into amyloid fibrils, and thereby enhance bactericidal activity of antibiotics. These findings will provide new insights into the multiple pharmacological properties of berberine in the treatment of microbial-generated amyloid involved diseases.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Staphylococcus Aureus; Barberine.

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#Ceftazidime – #avibactam or best available #therapy in patients with ceftazidime-resistant #Enterobacteriaceae and #Pseudomonas aeruginosa complicated UTI or … (The Lancet Infect Dis., abstract)

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

Articles

Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study

Prof Yehuda Carmeli, MD, Jon Armstrong, MSc, Peter J Laud, MSc, Paul Newell, MBBS, Greg Stone, PhD, Angela Wardman, BPharm, Leanne B Gasink, MD

Published Online: 20 April 2016 / Article has an altmetric score of 1 / DOI: http://dx.doi.org/10.1016/S1473-3099(16)30004-4

© 2016 Elsevier Ltd. All rights reserved.

 

Summary

Background

Carbapenems are frequently the last line of defence in serious infections due to multidrug-resistant Gram-negative bacteria, but their use is threatened by the growing prevalence of carbapenemase-producing pathogens. Ceftazidime-avibactam is a potential new agent for use in such infections. We aimed to assess the efficacy, safety, and tolerability of ceftazidime-avibactam compared with best available therapy in patients with complicated urinary tract infection or complicated intra-abdominal infection due to ceftazidime-resistant Gram-negative pathogens.

Methods

REPRISE was a pathogen-directed, international, randomised, open-label, phase 3 trial that recruited patients from hospitals across 16 countries worldwide. Eligible patients were aged 18–90 years with complicated urinary tract infection or complicated intra-abdominal infection caused by ceftazidime-resistant Enterobacteriaceae or Pseudomonas aeruginosa. Patients were randomised (1:1) to 5–21 days of treatment with either ceftazidime-avibactam (a combination of 2000 mg ceftazidime plus 500 mg avibactam, administered via a 2-h intravenous infusion every 8 h) or best available therapy. The primary endpoint was clinical response at the test-of-cure visit, 7–10 days after last infusion of study therapy, analysed in all patients who had at least one ceftazidime-resistant Gram-negative pathogen, as confirmed by the central laboratory, and who received at least one dose of study drug. Safety endpoints were assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01644643.

Findings

Between Jan 7, 2013, and Aug 29, 2014, 333 patients were randomly assigned, 165 to ceftazidime-avibactam and 168 to best available therapy. Of these, 154 assigned to ceftazidime-avibactam (144 with complicated urinary tract infection and ten with complicated intra-abdominal infection) and 148 assigned to best available therapy (137 with complicated urinary tract infection and 11 with complicated intra-abdominal infection) were analysed for the primary outcome. 163 (97%) of 168 patients in the best available therapy group received a carbapenem, 161 (96%) as monotherapy. The overall proportions of patients with a clinical cure at the test-of-cure visit were similar with ceftazidime-avibactam (140 [91%; 95% CI 85·6–94·7] of 154 patients) and best available therapy (135 [91%; 85·9–95·0] of 148 patients). 51 (31%) of 164 patients in the ceftazidime-avibactam group and 66 (39%) of 168 in the best available therapy group had an adverse event, most of which were mild or moderate in intensity. Gastrointestinal disorders were the most frequently reported treatment-emergent adverse events with both ceftazidime-avibactam (21 [13%] of 164 patients) and best available therapy (30 [18%] of 168 patients). No new safety concerns were identified for ceftazidime-avibactam.

Interpretation

These results provide evidence of the efficacy of ceftazidime-avibactam as a potential alternative to carbapenems in patients with ceftazidime-resistant Enterobacteriaceae and P aeruginosa.

Funding

AstraZeneca.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Carbapenem; Enterobacteriaceae; Pseudomonas A.

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The #Clinical #Efficacy of #Polymyxin #Monotherapy versus Non-validated Polymyxin Combination Therapy … in XDR Gram-Negative #Bacilli Infections (Antimicrob Agents Chemother., abstract)

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

The Clinical Efficacy of Polymyxin Monotherapy versus Non-validated Polymyxin Combination Therapy versus Validated Polymyxin Combination Therapy in Extensively Drug-Resistant Gram-Negative Bacilli Infections

Bingxuan Cai1, Yiying Cai1,2, Yi Xin Liew2, Nathalie Grace Chua2, Jocelyn Qi-Min Teo2, Tze-Peng Lim2, Asok Kurup3, Pui Lai Rachel Ee1, Thuan Tong Tan4, Winnie Lee2 and Andrea Lay-Hoon Kwa1,2,5#

Author Affiliations: 1Department of Pharmacy, Faculty of Science, National University of Singapore; 2Department of Pharmacy, Singapore General Hospital; 3Infectious Disease Care, Mount Elizabeth Hospital; 4Department of Infectious Diseases, Singapore General Hospital; 6Emerging Infectious Disease Program, Duke-National University of Singapore Medical School

 

ABSTRACT

Polymyxins have emerged as a last-resort treatment against the growing threat of extensively drug-resistant (XDR) gram negative bacilli (GNB) infections. Individualized polymyxin-based antibiotic combinations selected based on in vitro combination testing results may be required to optimize therapy. A retrospective cohort study of hospitalized patients receiving polymyxins for XDR GNB infections from 2009 – 2014 was conducted to compare treatment outcomes between patients receiving polymyxin monotherapy (MT), non-validated polymyxin combination therapy (NVCT), and in vitro combination testing validated polymyxin combination therapy (VCT). The primary and secondary outcomes were infection-related mortality and microbiological eradication respectively. Adverse drug reactions (ADRs) between treatment groups were assessed. A total of 291 patients (MT: n = 58; NVCT: n = 203; VCT: n = 30) were included. The overall infection-related mortality was 23.0% (67 patients). In the multivariable analysis, treatment of XDR GNB infections with MT [adjusted OR (aOR) 8.49; 95% CI 1.56 – 46.05] and NVCT (aOR 5.75; 95% CI 1.25 – 25.73) were associated with increased risk of infection-related mortality when compared to treatment with VCT. Higher APACHE II score (aOR 1.14; 95% CI 1.07 – 1.21) and higher CCI (aOR 1.28; 95% CI 1.11 – 1.47) were also independently associated with increased risk of infection-related mortality. There was no increase in ADRs observed in the VCT group. Using individualized antibiotic combination which was selected based on results of in vitro combination testing was associated with significantly lower infection-related mortality in XDR GNB infections. Future prospective randomized studies will be required to validate these findings.

FOOTNOTES

# Corresponding Author: Dr Andrea L. Kwa, Address: Blk 8 Level 2, Department of Pharmacy, Singapore General Hospital, Singapore 169608, Telephone No: +65 63266959, Fax No: +65 62202780, Email Address: andrea.kwa.l.h@sgh.com.sg

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Colistin.

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Complete #sequences of #mcr1 harboring #plasmids from #ESBL- and #carbapenemase-producing #Enterobacteriaceae (CPE) (Antimicrob Agents Chemother., abstract)

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

Complete sequences of mcr-1-harboring plasmids from extended spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae (CPE)

Aiqing Li1, Yong Yang1, Minhui Miao1, Kalyan D. Chavda2, José R. Mediavilla2, Xiaofang Xie1,  Ping Feng1, Yi-Wei Tang3, Barry N. Kreiswirth2, Liang Chen2 and Hong Du1

Author Affiliations: 1 Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, China. 2 Public Health Research Institute Tuberculosis Center, New Jersey medical school, Rutgers University, Newark, New Jersey 07103, USA. 3 Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA.

 

ABSTRACT

Here we completely sequenced four mcr-1-haboring plasmids, isolated from two ESBL-producing Escherichia coli and two carbapenemase-producing Klebsiella pneumoniae clinical isolates. The mcr-1-harboring plasmids, pMCR1-IncX4, from an ST2248 E. coli and two ST25 K. pneumoniae, were identical, belonging to the IncX4 incompatibility group, while the plasmid (pMCR1-IncI2) from an ST2085 E. coli belongs to the IncI2 group. A 2.6 kb nearly identical mcr-1-pap2 element was found to be shared by all mcr-1-carring plasmids.

FOOTNOTES

*Correspondent author: Dr. Liang Chen, E-mail: Chen11@njms.rutgers.edu; Or Dr. Hong Du: hong_du@126.com

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Colistin; Carbapenem.

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#Detection of the #plasmid-mediated #mcr1 #gene conferring #colistin #resistance in #human and #food isolates of #Salmonella enterica and #Escherichia coli in #England and #Wales (J Antimicrob Chemother., abstract)

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

Detection of the plasmid-mediated mcr-1 gene conferring colistin resistance in human and food isolates of Salmonella enterica and Escherichia coli in England and Wales

Michel Doumith, Gauri Godbole, Philip Ashton, Lesley Larkin, Tim Dallman, Martin Day, Michaela Day, Berit Muller-Pebody, Matthew J. Ellington, Elizabeth de Pinna, Alan P. Johnson, Katie L. Hopkins and Neil Woodford*

Author Affiliations: National Infection Service, Public Health England, London NW9 5EQ, UK

*Corresponding author. Tel: +44-(0)20-8327-6511; E-mail: neil.woodford@phe.gov.uk

Received January 12, 2016. Revision requested January 28, 2016. Revision received February 19, 2016. Accepted February 29, 2016.

 

Abstract

Objectives

In response to the first report of transmissible colistin resistance mediated by the mcr-1 gene in Escherichia coli and Klebsiella spp. from animals and humans in China, we sought to determine its presence in Enterobacteriaceae isolated in the UK.

Methods

The PHE archive of whole-genome sequences of isolates from surveillance collections, submissions to reference services and research projects was retrospectively analysed for the presence of mcr-1 using Genefinder. The genetic environment of the gene was also analysed.

Results

Rapid screening of the genomes of ∼24 000 Salmonella enterica, E. coli, Klebsiella spp., Enterobacter spp., Campylobacter spp. and Shigella spp. isolated from food or humans identified 15 mcr-1-positive isolates. These comprised: 10 human S. enterica isolates submitted between 2012 and 2015 (8 Salmonella Typhimurium, 1 Salmonella Paratyphi B var Java and 1 Salmonella Virchow) from 10 patients; 3 isolates of E. coli from 2 patients; and 2 isolates of Salmonella Paratyphi B var Java from poultry meat imported from the EU. The mcr-1 gene was located on diverse plasmids belonging to the IncHI2, IncI2 and IncX4 replicon types and its association with ISApl1 varied. Six mcr-1-positive S. enterica isolates were from patients who had recently travelled to Asia.

Conclusions

Analysis of WGS data allowed rapid confirmation of the presence of the plasmid-mediated colistin resistance gene mcr-1 in diverse genetic environments and plasmids. It has been present in E. coli and Salmonella spp. harboured by humans in England and Wales since at least 2012.

© Crown copyright 2016.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Colistin; E. Coli; Salmonella; Wales; England.

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#Aquaculture as yet another #environmental #gateway to the #development and #globalisation of #antimicrobial #resistance (The Lancet ID., abstract)

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

Personal View

Aquaculture as yet another environmental gateway to the development and globalisation of antimicrobial resistance

Prof Felipe C Cabello, MD, Prof Henry P Godfrey, MD, Prof Alejandro H Buschmann, PhD, Prof Humberto J Dölz, PhD

Published Online: 12 April 2016 / Article has an altmetric score of 11 / DOI: http://dx.doi.org/10.1016/S1473-3099(16)00100-6

© 2016 Elsevier Ltd. All rights reserved.

 

Summary

Aquaculture uses hundreds of tonnes of antimicrobials annually to prevent and treat bacterial infection. The passage of these antimicrobials into the aquatic environment selects for resistant bacteria and resistance genes and stimulates bacterial mutation, recombination, and horizontal gene transfer. The potential bridging of aquatic and human pathogen resistomes leads to emergence of new antimicrobial-resistant bacteria and global dissemination of them and their antimicrobial resistance genes into animal and human populations. Efforts to prevent antimicrobial overuse in aquaculture must include education of all stakeholders about its detrimental effects on the health of fish, human beings, and the aquatic ecosystem (the notion of One Health), and encouragement of environmentally friendly measures of disease prevention, including vaccines, probiotics, and bacteriophages. Adoption of these measures is a crucial supplement to efforts dealing with antimicrobial resistance by developing new therapeutic agents, if headway is to be made against the increasing problem of antimicrobial resistance in human and veterinary medicine.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance.

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#Detection of #mcr1 #colistin #resistance #gene in polyclonal E.coli isolates in Barcelona, #Spain, 2012 to 2015 (@eurosurveillanc, abstract)

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

Eurosurveillance, Volume 21, Issue 13, 31 March 2016 / Rapid communication

Detection of mcr-1 colistin resistance gene in polyclonal Escherichia coli isolates in Barcelona, Spain, 2012 to 2015

N Prim 1 , A Rivera 1 , J Rodríguez-Navarro 1 , M Español 1 , M Turbau 2 , P Coll 1 3 , B Mirelis 1 3

Author affiliations: 1. Microbiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 2. Emergency Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 3. Universitat Autònoma de Barcelona, Barcelona, Spain

Correspondence: Núria Prim (nprim@santpau.cat)

Citation style for this article: Prim N, Rivera A, Rodríguez-Navarro J, Español M, Turbau M, Coll P, Mirelis B. Detection of mcr-1 colistin resistance gene in polyclonal Escherichia coli isolates in Barcelona, Spain, 2012 to 2015. Euro Surveill. 2016;21(13):pii=30183. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.13.30183

Received:15 March 2016; Accepted:31 March 21

 

Abstract

Colistin resistance was detected in 53 of 10,011 Escherichia coli (0.5%) by prospective phenotypic testing of consecutive clinical isolates in a single hospital in Barcelona, Spain (2012–15). The mcr-1 gene was retrospectively identified by PCR and sequencing in 15 of 50 available isolates. Each isolate had a unique PFGE pattern except for two. This clonal diversity supports the hypothesis of horizontal dissemination of the mcr-1 gene in the local study population.

Keywords: Research; Abstracts; E. Coli; Antibiotics; Drugs Resistance; Colistin; Spain.

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