In Vitro Activity of #Minocycline against #US Isolates of #Acinetobacter baumannii – Acinetobacter calcoaceticus species complex, …: Results from the SENTRY Antimicrobial Surveillance Program (2014-2018) (Antimicrob Agents Chemother., abstract)

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

In Vitro Activity of Minocycline against U.S. Isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus species complex, Stenotrophomonas maltophilia, and Burkholderia cepacia complex: Results from the SENTRY Antimicrobial Surveillance Program (2014-2018)

Robert K. Flamm, Dee Shortridge, Mariana Castanheira, Helio S. Sader, Michael A. Pfaller

DOI: 10.1128/AAC.01154-19

 

ABSTRACT

We evaluated the activity of minocycline and comparator agents against a large number of Stenotrophomonas maltophilia (n = 1,289), Acinetobacter baumannii-Acinetobacter calcoaceticus species complex (n = 1,081), and Burkholderia cepacia complex (n = 101) collected during 2014 through 2018 from 87 U.S. medical centers spanning all nine census divisions. The isolates were collected primarily from hospitalized patients with pneumonia (1,632 isolates; 66.0% overall), skin and skin structure infections (354 isolates; 14.3% overall), bloodstream infections (266 isolates; 10.8% overall), urinary tract infections (126 isolates; 5.1% overall), intra-abdominal infections (61 isolates; 2.5% overall), and other infections (32 isolates; 1.3% overall). Against A. baumannii-A. calcoaceticus species complex, colistin was the most active agent exhibiting MIC50/90 values at ≤0.5/2 μg/ml and 92.4% susceptible. Minocycline ranked second in activity with MIC50/90 values at 0.25/8 μg/ml and susceptibility at 85.7%. Activity for these two agents was reduced against extensively drug-resistant and multidrug-resistant isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus species complex. Only two agents showed high levels of activity (susceptibility >90%) against S. maltophilia: minocycline (MIC50/90, 0.5/2 μg/ml; 99.5% susceptible) and trimethoprim-sulfamethoxazole (MIC50/90, ≤0.5/1 μg/ml; 94.6% susceptible). Minocycline was active against 92.8% (MIC90, 4 μg/ml) of trimethoprim-sulfamethoxazole-resistant S. maltophilia isolates. Various agents exhibited susceptibility rates of nearly 90% against B. cepacia complex: trimethoprim-sulfamethoxazole (MIC50/90, ≤0.5/2 μg/ml; 93.1% susceptible), ceftazidime (MIC50/90, 2/8 μg/ml; 91.0%), meropenem (MIC50/90, 2/8 μg/ml; 89.1%) and minocycline (MIC50/90, 2/8 μg/ml; 88.1% susceptible). These results indicate that minocycline is among the most active agents for these three problematic potential pathogen groups when tested against U.S. isolates.

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

Keywords: Antibiotics; Drugs Resistance; Minocycline; Colistin; Acinetobacter baumannii; Burkholderia cepacia; USA.

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#Assessment of the #potential for inducing #resistance in #MDR organisms from exposure to #minocycline, #rifampin and #chlorhexidine used to treat intravascular #devices (Antimicrob Agents Chemother., abstract)

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

Assessment of the potential for inducing resistance in multidrug resistant organisms from exposure to minocycline, rifampin and chlorhexidine used to treat intravascular devices.

Joel Rosenblatt, Nylev Vargas-Cruz, Ruth A. Reitzel, Issam I Raad

DOI: 10.1128/AAC.00040-19

 

ABSTRACT

To assess the potential for induction of antimicrobial resistance following repeated sub-inhibitory exposures to the combination Minocycline (M), Rifampin (R), and Chlorhexidine (CH), a total of 29 clinical microbial pathogenic isolates were repeatedly exposed to sub-inhibitory concentrations of M, R and CH for 20 passages. Minimum inhibitory concentrations (MICs) of the M, R and CH combination were assessed at each passage to evaluate the potential for resistance to have been induced. The combination of M, R and CH showed significant antimicrobial efficacy and synergy against organisms resistant to all 3 individual components (MIC ≥16 μg/mL for M, or MIC ≥4 μg/mL for R or CH). Among the organisms originally resistant to 2 or more individual components and the organisms originally susceptible to 2 or more individual components, there was no evidence that organisms became resistant following 20 repeated sub-inhibitory exposure cycles to the triple combination. The risk of resistance developing to the triple combination is extremely low because microbes are inhibited or killed before resistances can simultaneously emerge to all three agents. Surveillance studies monitoring development of resistance should be conducted in a clinical setting.

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

Keywords: Antibiotics; Drugs Resistance; Minocycline; Rifampin; Chlorhexidine.

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#Fluoroquinolone #resistance in #carbapenem-resistant #Elizabethkingia anophelis: phenotypic and genotypic characteristics of clinical isolates … (J Antimicrob Chemother., abstract)

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

Fluoroquinolone resistance in carbapenem-resistant Elizabethkingia anophelis: phenotypic and genotypic characteristics of clinical isolates with topoisomerase mutations and comparative genomic analysis

Ming-Jr Jian, Yun-Hsiang Cheng, Hsing-Yi Chung, Yu-Hsuan Cheng, Hung-Yi Yang, Chih-Sin Hsu, Cherng-Lih Perng, Hung-Sheng Shang

Journal of Antimicrobial Chemotherapy, dkz045, https://doi.org/10.1093/jac/dkz045

Published: 04 March 2019

 

Abstract

Background

MDR Elizabethkingia anophelis strains are implicated in an increasing number of healthcare-associated infections worldwide, including a recent cluster of E. anophelis infections in the Midwestern USA associated with significant morbidity and mortality. However, there is minimal information on the antimicrobial susceptibilities of E. anophelis strains or their antimicrobial resistance to carbapenems and fluoroquinolones.

Objectives

Our aim was to examine the susceptibilities and genetic profiles of clinical isolates of E. anophelis from our hospital, characterize their carbapenemase genes and production of MBLs, and determine the mechanism of fluoroquinolone resistance.

Methods

A total of 115 non-duplicated isolates of E. anophelis were examined. MICs of antimicrobial agents were determined using the Sensititre 96-well broth microdilution panel method. QRDR mutations and MBL genes were identified using PCR. MBL production was screened for using a combined disc test.

Results

All E. anophelis isolates harboured the blaGOB and blaB genes with resistance to carbapenems. Antibiotic susceptibility testing indicated different resistance patterns to ciprofloxacin and levofloxacin in most isolates. Sequencing analysis confirmed that a concurrent GyrA amino acid substitution (Ser83Ile or Ser83Arg) in the hotspots of respective QRDRs was primarily responsible for high-level ciprofloxacin/levofloxacin resistance. Only one isolate had no mutation but a high fluoroquinolone MIC.

Conclusions

Our study identified a strong correlation between antibiotic susceptibility profiles and mechanisms of fluoroquinolone resistance among carbapenem-resistant E. anophelis isolates, providing an important foundation for continued surveillance and epidemiological analyses of emerging E. anophelis opportunistic infections. Minocycline or ciprofloxacin has the potential for treatment of severe E. anophelis infections.

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Elizabethkingia anophelis; Minocycline; Ciprofloxacin.

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Novel partners with #colistin to increase its in vivo therapeutic effectiveness and prevent the occurrence of colistin #resistance in #NDM- and #MCR-co-producing #Ecoli in a murine infection model (J Antimicrob Chemother., abstract)

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

Novel partners with colistin to increase its in vivotherapeutic effectiveness and prevent the occurrence of colistin resistance in NDM- and MCR-co-producing Escherichia coli in a murine infection model

Yang Yu, Timothy R Walsh, Run-Shi Yang, Mei Zheng, Meng-Chao Wei, Jonathan M Tyrrell, Yang Wang, Xiao-Ping Liao, Jian Sun, Ya-Hong Liu

Journal of Antimicrobial Chemotherapy, dky413, https://doi.org/10.1093/jac/dky413

Published: 20 October 2018

 

Abstract

Objectives

The emergence of NDM- and MCR-1-co-producing Escherichia coli has compromised the use of carbapenems and colistin, which are critically important in clinical therapy, and represents a severe threat to public health worldwide. Here, we demonstrate synergism of colistin combined with existing antibiotics as a potential strategy to overcome XDR E. coli co-harbouring NDM and MCR-1 genes.

Methods

To comprehensively evaluate their combined activity, antibiotic combinations were tested against 34 different E. coli strains carrying both NDM and MCR-1 genes. Antibiotic resistance profiles and molecular characteristics were investigated by susceptibility testing, PCR, MLST, S1-PFGE and WGS. Antibiotic synergistic efficacy was evaluated through in vitro chequerboard experiments and dose–response assays. A mouse model was used to confirm active combination therapies. Additionally, combinations were tested for their ability to prevent high-level colistin-resistant mutants (HLCRMs).

Results

Combinations of colistin with rifampicin, rifabutin and minocycline showed synergistic activity against 34 XDR NDM- and MCR-1-co-producing E. coli strains, restoring, in part, susceptibility to both colistin and the partnering antibiotics. The therapeutic effectiveness of colistin combined with rifampicin or minocycline was demonstrated in a mouse model. Furthermore, colistin plus rifampicin showed significant activity in preventing the occurrence of HLCRMs.

Conclusions

The synergism of colistin in combinations with rifampicin, rifabutin or minocycline offers viable therapeutic alternatives against XDR NDM- and MCR-positive E. coli.

Issue Section: ORIGINAL RESEARCH

© 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: Research; Abstracts; Antibiotics; Drugs Resistance; Colistin; E. Coli; Rifampicin; Rifabutin; Minocycline; MCR; NDM.

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#Clinical manifestations, molecular characteristics, #antimicrobial susceptibility patterns and contributions of target gene mutation to #fluoroquinolone resistance in #Elizabethkingia anophelis (J Antimicrob Chemother., abstract)

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

Clinical manifestations, molecular characteristics, antimicrobial susceptibility patterns and contributions of target gene mutation to fluoroquinolone resistance in Elizabethkingia anophelis

Jiun-Nong Lin, Chung-Hsu Lai, Chih-Hui Yang, Yi-Han Huang, Hsi-Hsun Lin

Journal of Antimicrobial Chemotherapy, dky197, https://doi.org/10.1093/jac/dky197

Published: 28 May 2018

 

Abstract

Objectives

Elizabethkingia anophelis has recently emerged as a cause of life-threatening infections in humans. We aimed to investigate the clinical and molecular characteristics of E. anophelis.

Methods

A clinical microbiology laboratory database was searched to identify patients with Elizabethkingia infections between 2005 and 2016. Isolates were re-identified and their species were confirmed using 16S rRNA gene sequencing. Patients with E. anophelis infections were included in this study. Clinical information, antimicrobial susceptibility and mutations in DNA gyrase and topoisomerase IV were analysed.

Results

A total of 67 patients were identified to have E. anophelis infections, including 47 men and 20 women, with a median age of 61 years. Comorbidity was identified in 85.1% of the patients. Among the 67 E. anophelis isolates, 40 (59.7%) were isolated from blood. The case fatality rate was 28.4%. Inappropriate empirical antimicrobial therapy was an independent risk factor for mortality (adjusted OR = 10.01; 95% CI = 1.20–83.76; P = 0.034). The isolates were ‘not susceptible’ to multiple antibiotics. All the isolates were susceptible to minocycline. Susceptibilities to ciprofloxacin and levofloxacin were 4.5% and 58.2%, respectively. Mutations in DNA gyrase subunit A were identified in 11 isolates that exhibited high-level fluoroquinolone resistance.

Conclusions

Minocycline has the potential to be the drug of choice in patients with E. anophelis infections. Additional investigations are needed to determine the optimal antimicrobial agents to treat this life-threatening infection.

Issue Section: ORIGINAL RESEARCH

© 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/about_us/legal/notices)

Keywords: Antibiotics; Drugs Resistance; Fluoroquinolones; Minocycline; Elizabethkingia anophelis.

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Novel #activities of safe-in-human broad-spectrum #antiviral agents (Antiviral Res., abstract)

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

Antiviral Res. 2018 Apr 23. pii: S0166-3542(18)30098-6. doi: 10.1016/j.antiviral.2018.04.016. [Epub ahead of print]

Novel activities of safe-in-human broad-spectrum antiviral agents.

Ianevski A1, Zusinaite E2, Kuivanen S3, Strand M4, Lysvand H5, Teppor M6, Kakkola L7, Paavilainen H8, Laajala M9, Kallio-Kokko H10, Valkonen M11, Kantele A12, Telling K13, Lutsar I14, Letjuka P15, Metelitsa N16, Oksenych V17, Bjørås M18, Nordbø SA19, Dumpis U20, Vitkauskiene A21, Öhrmalm C22, Bondeson K23, Bergqvist A24, Aittokallio T25, Cox RJ26, Evander M27, Hukkanen V28, Marjomaki V29, Julkunen I30, Vapalahti O31, Tenson T32, Merits A33, Kainov D34.

Author information: 1 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, Norway. Electronic address: aleksandr.ianevski@helsinki.fi. 2 Institute of Technology, University of Tartu, Tartu 50090, Estonia. Electronic address: eva.zusinaite@gmail.com. 3 Department of Virology, University of Helsinki, Helsinki 00014, Finland. Electronic address: suvi.kuivanen@helsinki.fi. 4 Department of Clinical Microbiology, Umeå University, Umeå 90185, Sweden. Electronic address: marten.strand@umu.se. 5 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7491, Norway. Electronic address: hilde.lysvand@ntnu.no. 6 Institute of Technology, University of Tartu, Tartu 50090, Estonia. Electronic address: mona.teppor@gmail.com. 7 Institute of Biomedicine, University of Turku, Turku 20520, Finland. Electronic address: laura.kakkola@utu.fi. 8 Institute of Biomedicine, University of Turku, Turku 20520, Finland. Electronic address: hojpaa@utu.fi. 9 Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä 40500, Finland. Electronic address: mira.a.laajala@jyu.fi. 10 Department of Virology and Immunology, University of Helsinki, Helsinki University Hospital, Helsinki 00014, Finland. Electronic address: hannimari.kallio-kokko@hus.fi. 11 Helsinki University Hospital, Helsinki 00014, Finland. Electronic address: miia.valkonen@hus.fi. 12 Helsinki University Hospital, Helsinki 00014, Finland. Electronic address: anu.kantele@helsinki.fi. 13 Institute of Medical Microbiology, University of Tartu, Tartu 50411, Estonia. Electronic address: kaidi.telling@ut.ee. 14 Institute of Medical Microbiology, University of Tartu, Tartu 50411, Estonia. Electronic address: irja.lutsar@ut.ee. 15 Narva Haigla, Narva 20104, Estonia. Electronic address: ellipellip@mail.ru. 16 Narva Haigla, Narva 20104, Estonia. Electronic address: nmetelitsa@gmail.com. 17 St. Olavs Hospital, Trondheim University Hospital, Clinic of Medicine, Trondheim 7006, Norway. Electronic address: valentyn.oksenych@ntnu.no. 18 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7491, Norway. Electronic address: magnar.bjoras@ntnu.no. 19 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7491, Norway; Department of Medical Microbiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim 7006, Norway. Electronic address: svein.a.nordbo@ntnu.no. 20 Pauls Stradins Clinical University Hospital, Riga 1002, Latvia. Electronic address: uga.dumpis@gmail.com. 21 Department of Laboratory Medicine, Lithuanian University of Health Science, Kaunas 44307, Lithuania. Electronic address: astra.vitkauskiene@kaunoklinikos.lt. 22 Department of Medical Sciences, Uppsala University, Uppsala 75309, Sweden. Electronic address: christina.ohrmalm@akademiska.se. 23 Department of Medical Sciences, Uppsala University, Uppsala 75309, Sweden. Electronic address: kare.bondeson@akademiska.se. 24 Department of Medical Sciences, Uppsala University, Uppsala 75309, Sweden. Electronic address: anders.bergqvist@akademiska.se.  25 Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland; Department of Mathematics and Statistics, University of Turku, Turku 20014, Finland. Electronic address: tero.aittokallio@fimm.fi. 26 Influenza Centre, Department of Clinical Science, University of Bergen, Bergen 5021, Norway. Electronic address: rebecca.cox@uib.no. 27 Department of Clinical Microbiology, Umeå University, Umeå 90185, Sweden. Electronic address: magnus.evander@umu.se. 28 Institute of Biomedicine, University of Turku, Turku 20520, Finland. Electronic address: veijo.hukkanen@utu.fi. 29 Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä 40500, Finland. Electronic address: varpu.s.marjomaki@jyu.fi. 30 Institute of Biomedicine, University of Turku, Turku 20520, Finland. Electronic address: ilkka.julkunen@utu.fi. 31 Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki 00014, Finland; Department of Veterinary Biosciences, University of Helsinki, Helsinki 00014, Finland. Electronic address: olli.vapalahti@helsinki.fi. 32 Institute of Technology, University of Tartu, Tartu 50090, Estonia. Electronic address: tanel.tenson@ut.ee. 33 Institute of Technology, University of Tartu, Tartu 50090, Estonia. Electronic address: andres.merits@ut.ee. 34 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7028, Norway; Institute of Technology, University of Tartu, Tartu 50090, Estonia. Electronic address: denikaino@gmail.com.

 

Abstract

According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.

PMID: 29698664 DOI: 10.1016/j.antiviral.2018.04.016

Keywords: Emerging Diseases; Zika Virus; RVF; HIV; Echovirus 1; Antivirals; Dalbavancin; Ezetimibe; Azacitidine; Cyclosporine; Minocycline; Oritavancin; Ritonavir.

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