#Plasmid-Mediated #mcr-1 #Colistin #Resistance in #Escherichia coli from a Black Kite in #Russia (Antimicrob Agents Chemother., abstract)

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

Plasmid-Mediated mcr-1 Colistin Resistance in Escherichia coli from a Black Kite in Russia

Hassan Tarabai, Adam Valcek, Ivana Jamborova, Sergey V. Vazhov, Igor V. Karyakin, Rainer Raab, Ivan Literak, Monika Dolejska

DOI: 10.1128/AAC.01266-19

 

ABSTRACT

The gene mcr-1 conferring resistance to last-line antibiotic colistin has been reported globally. Here we describe the first detection of plasmid-mediated colistin resistance in Russian wildlife, an isolate of Escherichia coli sequence type 2280 from a black kite (Milvus migrans), scavenging raptor. Whole genome sequencing and plasmid transferability experiments revealed that mcr-1.1 was located on a conjugative IncI2 plasmid pDR164 (59891 bp). Migratory Black Kites may contribute to the global spread of mobile colistin resistance.

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

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1; E. Coli; Wild Birds; Russia.

——

Advertisements

#Synergistic #combinations and repurposed #antibiotics active against the #pandrug #resistant #Klebsiella pneumoniae #Nevada strain (Antimicrob Agents Chemother., abstract)

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

Synergistic combinations and repurposed antibiotics active against the pandrug-resistant Klebsiella pneumoniae Nevada strain

Thea Brennan-Krohn [MD], James E. Kirby [MD]

DOI: 10.1128/AAC.01374-19

 

ABSTRACT

In early 2017, the Centers for Disease Control and Prevention issued an alarming report describing a woman in Nevada who died in the setting of infection with a pan-resistant Klebsiella pneumoniae isolate that harbored an NDM-1 enzyme (AR-0636) and was colistin resistant as a result of inactivation of the mgrB regulator gene (1, 2).…

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

Keywords: Antibiotics; Drugs Resistance; Klebsiella pneumoniae; USA; Nevada.

——

#Repurposing of #ribavirin as an adjunct #therapy against invasive #Candida strains: In vitro study (Antimicrob Agents Chemother., abstract)

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

Repurposing of ribavirin as an adjunct therapy against invasive Candidastrains: In vitro study

Hanane Yousfi, Carole Cassagne, Stéphane Ranque, Jean-marc Rolain, Fadi Bittar

DOI: 10.1128/AAC.00263-19

 

ABSTRACT

The use of antifungal agents in clinical settings is limited by the appearance of drug resistance and adverse side effects. There is, therefore, an urgent need to develop new drugs to strengthen the treatment of invasive fungal diseases. The aim of this study is to describe the potential repurposing of ribavirin as an adjunct therapy against Candida spp.

Primary screening of Prestwick chemical library against Candida albicans ATCC 90028 and fluconazole-resistant Candida albicans was performed. Subsequently, we evaluated the response of 100 Candida spp strains to ribavirin, an antiviral agent, using the broth microdilution method as recommended by CLSI. We checked the involvement of efflux pump activity in the development of ribavirin-resistance. We studied time-kill curves and performed a checkerboard assay for ribavirin-antifungals combinations study.

Twenty-one nonstandard antifungal compounds were identified, including ribavirin. Ribavirin had, in vitro, an antifungal activity against 63 Candida strains including C. albicans, C. parapsilosis and C. tropicalis, with a minimum inhibitory concentrations (MICs) ranging from 0.37 to 3.02 μg/ml, while MICs for C. krusei, C. glabrata, C. lusitaniae and some C. albicans remain high (≥ 24.16 μg/ml). No relation was observed between efflux pump activity and ribavirin-resistance. Ribavirin exhibited a fungistatic activity against multidrug-resistant (MDR) C. albicans and a fungicidal activity against C. parapsilosis strain. In addition, ribavirin acted synergistically with azoles against Candida strains for which ribavirin MICs were < 24.4 μg/ml.

This study highlights the potential clinical application of ribavirin, alone or in association with other antifungal agents, as an adjunct anti-Candida drug.

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

Keywords: Antibiotics; Drugs Resistance; Candida spp.; Ribavirin.

——

A #MDR #Plasmid pIMP26, Carrying blaIMP-26, fosA5, blaDHA-1, and qnrB4 in #Enterobacter cloacae (Sci Rep., abstract)

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

Article | OPEN | Published: 15 July 2019

A Multidrug Resistance Plasmid pIMP26, Carrying blaIMP-26, fosA5, blaDHA-1, and qnrB4 in Enterobacter cloacae

Su Wang,  Kaixin Zhou, Shuzhen Xiao, Lianyan Xie, Feifei Gu, Xinxin Li, Yuxing Ni, Jingyong Sun & Lizhong Han

Scientific Reports, volume 9, Article number: 10212 (2019)

 

Abstract

IMP-26 was a rare IMP variant with more carbapenem-hydrolyzing activities, which was increasingly reported now in China. This study characterized a transferable multidrug resistance plasmid harboring blaIMP-26 from one Enterobacter cloacae bloodstream isolate in Shanghai and investigated the genetic environment of resistance genes. The isolate was subjected to antimicrobial susceptibility testing and multilocus sequence typing using broth microdilution method, Etest and PCR. The plasmid was analyzed through conjugation experiments, S1-nuclease pulsed-field gel electrophoresis and hybridization. Whole genome sequencing and sequence analysis was conducted for further investigation of the plasmid. E. cloacae RJ702, belonging to ST528 and carrying blaIMP-26, blaDHA-1, qnrB4 and fosA5, was resistant to almost all β-lactams, but susceptible to quinolones and tigecycline. The transconjugant inherited the multidrug resistance. The resistance genes were located on a 329,420-bp IncHI2 conjugative plasmid pIMP26 (ST1 subtype), which contained trhK/trhV, tra, parA and stbA family operon. The blaIMP-26 was arranged following intI1. The blaDHA-1 and qnrB4cluster was the downstream of ISCR1, same as that in p505108-MDR. The fosA5 cassette was mediated by IS4. This was the first report on complete nucleotide of a blaIMP-26-carrying plasmid in E. cloacae in China. Plasmid pIMP26 hosted high phylogenetic mosaicism, transferability and plasticity.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; Enterobacter cloacae; Shanghai; China; Quinolones; Tigecycline.

——

#Azithromycin, a 15-membered #macrolide #antibiotic, inhibits #influenza A #H1N1pdm09 virus #infection by interfering with virus internalization process (J Antibit (Tokyo), abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Antibiot (Tokyo). 2019 Jul 12. doi: 10.1038/s41429-019-0204-x. [Epub ahead of print]

Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process.

Tran DH1,2, Sugamata R1,2,3, Hirose T4, Suzuki S1,2,3, Noguchi Y4, Sugawara A4,5, Ito F2, Yamamoto T2, Kawachi S2,3, Akagawa KS4, Ōmura S4, Sunazuka T4, Ito N6, Mimaki M6, Suzuki K7,8,9.

Author information: 1 Department of Health Protection, Graduate School of Medicine, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 2 Asia International Institute of Infectious Disease Control (ADC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 3 General Medical Education and Research Center (G-MEC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 4 Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo, 108-8641, Japan. 5 Graduate School of Pharmaceutical Sciences, Tohoku University, Aza-Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan. 6 The Pediatric Department, Teikyo Hospital University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 7 Department of Health Protection, Graduate School of Medicine, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp. 8 Asia International Institute of Infectious Disease Control (ADC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp. 9 General Medical Education and Research Center (G-MEC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp.

 

Abstract

The pandemic influenza 2009 (A(H1N1)pdm09) virus currently causes seasonal and annual epidemic outbreaks. The widespread use of anti-influenza drugs such as neuraminidase and matrix protein 2 (M2) channel inhibitors has resulted in the emergence of drug-resistant influenza viruses. In this study, we aimed to determine the anti-influenza A(H1N1)pdm09 virus activity of azithromycin, a re-positioned macrolide antibiotic with potential as a new anti-influenza candidate, and to elucidate its underlying mechanisms of action. We performed in vitro and in vivo studies to address this. Our in vitro approaches indicated that progeny virus replication was remarkably inhibited by treating viruses with azithromycin before infection; however, azithromycin administration after infection did not affect this process. We next investigated the steps inhibited by azithromycin during virus invasion. Azithromycin did not affect attachment of viruses onto the cell surface, but blocked internalization into host cells during the early phase of infection. We further demonstrated that azithromycin targeted newly budded progeny virus from the host cells and inactivated their endocytic activity. This unique inhibitory mechanism has not been observed for other anti-influenza drugs, indicating the potential activity of azithromycin before and after influenza virus infection. Considering these in vitro observations, we administered azithromycin intranasally to mice infected with A(H1N1)pdm09 virus. Single intranasal azithromycin treatment successfully reduced viral load in the lungs and relieved hypothermia, which was induced by infection. Our findings indicate the possibility that azithromycin could be an effective macrolide for the treatment of human influenza.

PMID:  31300721  DOI: 10.1038/s41429-019-0204-x

Keywords: Antibiotics; Azithromycin; Influenza A; H1N1pdm09.

——

Successful #treatment with #daptomycin and #ceftaroline of #MDR #Staphylococcus aureus native #valve #endocarditis: a case report (J Antimicrob Chemother., abstract)

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

Successful treatment with daptomycin and ceftaroline of MDR Staphylococcus aureus native valve endocarditis: a case report

François-Régis Duss, Cristina Garcia de la Mària, Antony Croxatto, Stefano Giulieri, Frédéric Lamoth, Oriol Manuel, José M Miró

Journal of Antimicrobial Chemotherapy, dkz253, https://doi.org/10.1093/jac/dkz253

Published:  11 July 2019

 

Abstract

Objectives

The best therapeutic approach for treating MRSA endocarditis remains unknown, particularly in cases of high vancomycin MICs. We report here a case of daptomycin-non-susceptible, ceftaroline-resistant and fosfomycin-resistant MRSA native left valve endocarditis that was successfully treated with valve repair and a combination of high-dose daptomycin and ceftaroline.

Methods

Antimicrobial testing of the clinical strain was performed using Etest and microdilution broth methods. Time–kill and chequerboard methodologies were used to test the activity of antibiotic combinations.

Results

By Etest, the MIC of vancomycin was 2 mg/L, the MIC of daptomycin was 2 mg/L, the MIC of fosfomycin was 1024 mg/L and the MIC of ceftaroline was 1.5 mg/L. At the standard inoculum (105 cfu/mL), the three combinations of daptomycin plus ceftaroline, cloxacillin or fosfomycin were synergistic and bactericidal. However, when these combinations were tested using a higher inoculum (108 cfu/mL), all combinations were synergistic, but only daptomycin plus ceftaroline had bactericidal activity.

Conclusions

These results confirmed a synergistic effect between daptomycin plus ceftaroline and increased bactericidal activity against MRSA, suggesting that this combination may be effective for the treatment of invasive MRSA infection. Our experience highlights the potential clinical use of synergy testing to guide difficult treatment decisions in patients with MDR MRSA infection.

Topic: endocarditis – vancomycin – staphylococcus aureus – cloxacillin – endocarditis, infectious, native valve – daptomycin – fosfomycin – methicillin-resistant staphylococcus aureus – ceftaroline – malnutrition-inflammation-cachexia syndrome

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; Staphylococcus aureus; Endocarditis; Ceftaroline; Daptomycin.

——

Activity of #cefepime / #zidebactam (WCK 5222) against #Enterobacteriaceae, #Pseudomonas aeruginosa and #Acinetobacter baumannii endemic to #NYC #medical centres (J Antimicrob Chemother., abstract)

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

Activity of cefepime/zidebactam (WCK 5222) against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii endemic to New York City medical centres

Zeb Khan, Alejandro Iregui, David Landman, John Quale

Journal of Antimicrobial Chemotherapy, dkz294, https://doi.org/10.1093/jac/dkz294

Published: 11 July 2019

 

Abstract

Background

The combination of cefepime and zidebactam (WCK5222), a novel β-lactam enhancer, has demonstrated activity against a wide variety of Gram-negative pathogens and is currently under clinical evaluation.

Objectives

To examine the activity of cefepime/zidebactam against: (i) a contemporary collection of Gram-negative isolates from New York City; (ii) a collection of carbapenem-resistant clinical isolates; and (iii) a collection of isolates with characterized resistance mechanisms.

Methods

Susceptibility tests were performed using broth microdilution for cefepime, zidebactam and cefepime/zidebactam (1:1).

Results

More than 99% of a contemporary collection of Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. had cefepime/zidebactam MICs ≤2 mg/L, the susceptibility breakpoint for cefepime. For K. pneumoniae, the acquisition of blaKPC resulted in increased MICs, although MICs remained ≤2 mg/L for 90% of KPC-possessing isolates. Overall for Pseudomonas aeruginosa, 98% of isolates had MICs ≤8 mg/L and MICs were affected by increased expression of ampC. For carbapenem-resistant P. aeruginosa, 78% of isolates had cefepime/zidebactam MICs ≤8 mg/L. The activity of cefepime/zidebactam against Acinetobacter baumannii was lower, with 85% of all isolates and 34% of carbapenem-resistant isolates with MICs ≤8 mg/L (cefepime interpretative criteria).

Conclusions

Cefepime/zidebactam demonstrated excellent activity against Enterobacteriaceae and P. aeruginosa, although activity was reduced in carbapenem-non-susceptible isolates. The activity against A. baumannii was reduced and studies examining the therapeutic efficacy in strains with high cefepime/zidebactam MICs are warranted.

Topic:  pseudomonas aeruginosa – cefepime – enterobacter – enterobacteriaceae – new york city – acinetobacter baumannii – bacterial carbapenemase resistance blakpc gene – malnutrition-inflammation-cachexia syndrome – 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; Carbapenem; Enterobacteriaceae; Pseudomonas aeruginosa; Acinetobacter baumannii; Cefepine; Zidebactam; USA; NYC.

——