#Antibiotics: past, present and future (Curr Opin Microbiol., abstract)

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

Curr Opin Microbiol. 2019 Nov 13;51:72-80. doi: 10.1016/j.mib.2019.10.008. [Epub ahead of print]

Antibiotics: past, present and future.

Hutchings M1, Truman A2, Wilkinson B3.

Author information: 1 School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK. Electronic address: m.hutchings@uea.ac.uk. 2 Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK. Electronic address: andrew.truman@jic.ac.uk. 3 Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK. Electronic address: barrie.wilkinson@jic.ac.uk.

 

Abstract

The first antibiotic, salvarsan, was deployed in 1910. In just over 100 years antibiotics have drastically changed modern medicine and extended the average human lifespan by 23 years. The discovery of penicillin in 1928 started the golden age of natural product antibiotic discovery that peaked in the mid-1950s. Since then, a gradual decline in antibiotic discovery and development and the evolution of drug resistance in many human pathogens has led to the current antimicrobial resistance crisis. Here we give an overview of the history of antibiotic discovery, the major classes of antibiotics and where they come from. We argue that the future of antibiotic discovery looks bright as new technologies such as genome mining and editing are deployed to discover new natural products with diverse bioactivities. We also report on the current state of antibiotic development, with 45 drugs currently going through the clinical trials pipeline, including several new classes with novel modes of action that are in phase 3 clinical trials. Overall, there are promising signs for antibiotic discovery, but changes in financial models are required to translate scientific advances into clinically approved antibiotics.

Copyright © 2019 Elsevier Ltd. All rights reserved.

PMID: 31733401 DOI: 10.1016/j.mib.2019.10.008

Keywords: Antibiotics; Drugs Resistance.

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Treatment of Highly Pathogenic #H7N9 Virus-Infected Mice with #Baloxavir Marboxil (Viruses, abstract)

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

Viruses. 2019 Nov 15;11(11). pii: E1066. doi: 10.3390/v11111066.

Treatment of Highly Pathogenic H7N9 Virus-Infected Mice with Baloxavir Marboxil.

Kiso M1, Yamayoshi S1, Furusawa Y1, Imai M1, Kawaoka Y1,2,3.

Author information: 1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. 2 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA. 3 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.

 

Abstract

Viral neuraminidase inhibitors show limited efficacy in mice infected with H7N9 influenza A viruses isolated from humans. Although baloxavir marboxil protected mice from lethal challenge infection with a low pathogenic avian influenza H7N9 virus isolated from a human, its efficacy in mice infected with a recent highly pathogenic version of H7N9 human isolates is unknown. Here, we examined the efficacy of baloxavir marboxil in mice infected with a highly pathogenic human H7N9 virus, A/Guangdong/17SF003/2016. Treatment of infected mice with a single 1.5 mg/kg dose of baloxavir marboxil protected mice from the highly pathogenic human H7N9 virus infection as effectively as oseltamivir treatment at 50 mg/kg twice a day for five days. Daily treatment for five days at 15 or 50 mg/kg of baloxavir marboxil showed superior therapeutic efficacy, largely preventing virus replication in respiratory organs. These results indicate that baloxavir marboxil is a valuable candidate treatment for human patients suffering from highly pathogenic H7N9 virus infection.

KEYWORDS: H7N9; baloxavir marboxil; highly pathogenic; influenza

PMID: 31731678 DOI: 10.3390/v11111066

Keywords: Antivirals; Avian Influenza; H7N9; Baloxavir Marboxil; Animal models.

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#Erythromycin Estolate Inhibits #Zika Virus #Infection by Blocking Viral Entry as a Viral Inactivator (Viruses, abstract)

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

Viruses. 2019 Nov 15;11(11). pii: E1064. doi: 10.3390/v11111064.

Erythromycin Estolate Inhibits Zika Virus Infection by Blocking Viral Entry as a Viral Inactivator.

Wang X1, Xia S1, Zou P1, Lu L1.

Author information: 1 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 200032, China.

 

Abstract

Recently, Zika virus (ZIKV) has attracted much attention in consideration of its association with severe neurological complications including fetal microcephaly. However, there are currently no prophylactic vaccines or therapeutic drugs approved for clinical treatments of ZIKV infection. To determine the potential anti-ZIKV inhibitors, we screened a library of clinical drugs with good safety profiles. Erythromycin estolate (Ery-Est), one of the macrolide antibiotics, was found to effectively inhibit ZIKV infection in different cell types and significantly protect A129 mice from ZIKV-associated neurological signs and mortality. Through further investigation, Ery-Est was verified to inhibit ZIKV entry by disrupting the integrity of the viral membrane which resulted in the loss of ZIKV infectivity. Furthermore, Ery-Est also showed inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Thus, Ery-Est may be a promising drug for patients with ZIKV infection, particularly pregnant women.

KEYWORDS: ZIKV; erythromycin estolate; inactivator; viral entry inhibitor

PMID: 31731598 DOI: 10.3390/v11111064

Keywords: Zika Virus; Antibiotics; Macrolides; Erythromycin.

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Next generation #sequencing of #human #enterovirus strains from an #outbreak of #EVA71 shows applicability to outbreak investigations (J Clin Invest., abstract)

[Source: Journal of Clinical Investigation, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology / Available online 17 November 2019, 104216 / In Press, Journal Pre-proof

Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations

Sacha Stelzer-Braid a,b, Matthew Wynn a, Richard Chatoor a, Matthew Scotchc d,e, Vidiya Ramachandran f, Hooi-Ling Teoh g, h, Michelle A.Farrarg h, Hugo Sampaio g,h, Peter Ian Andrews g,h, Maria E.Craig a,h, C. Raina Mac Intyre c,i,j, Hemalatha Varadhan k, Alison Kesson l, Philip N.Britton l,m, James Newcomb e,n, William D.Rawlinson a,b,h

{a} Virology Research Laboratory, Serology and Virology Division (SAViD), NSW Health Pathology, Prince of Wales Hospital, Sydney, NSW 2031, Australia; {b} School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia; {c} College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; {d} Center for Environmental Health Engineering, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; {e} School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW 2033, Australia; {f} Serology and Virology Division (SAViD), NSW Health Pathology East, Department of Microbiology, Prince of Wales Hospital, Sydney, NSW 2031, Australia; {g} Department of Neurology, Sydney Children’s Hospital, Sydney, Australia; {h} School of Women’s and Children’s Health, University of New South Wales Medicine, Sydney, NSW 2052, Australia; {i} Biosecurity Program, Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia; {j} Watts College of Public Service and Community Solutions, Arizona State University, Phoenix, AZ 85004, USA; {k} NSW Health Pathology, John Hunter Hospital, Newcastle, United Kingdom; {l} Department of Infectious Diseases and Microbiology, The Children’s Hospital at Westmead, Australia; {m} Marie Bashir Institute, University of Sydney, Australia; {n} Pathology North, Royal North Shore Hospital, St Leonards, Australia

Received 24 April 2019, Revised 8 October 2019, Accepted 11 November 2019, Available online 17 November 2019.

DOI: https://doi.org/10.1016/j.jcv.2019.104216

 

Highlights

  • Near full-length genome analysis using next generation sequencing identified EV-A71 and other enterovirus A and B subtypes circulating.
  • The Sydney EV-A71 2013 strain was very similar to EV-A71 circulating in China and Vietnam during the previous year.
  • Strains causing more severe clinical manifestations grouped together phylogenetically.

 

Abstract

Background

The most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications.

Objectives

To characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype.

Study design

We performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses.

Results

We amplified and sequenced 23/63 (37 %) genomes, and identified the majority (61 %) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community.

Conclusions

This is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design.

Keywords: Enterovirus – EV-A71 – Phylogeny – Hand, foot and mouth disease – Whole genome sequencing – Australia

© 2019 Published by Elsevier B.V.

Keywords: HFMD; Enterovirus; EV-A71; Australia.

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The global burden of premature #mortality due to the Middle East respiratory syndrome (#MERS) using standard expected years of life lost, 2012 to 2019 (BMC Public Health, abstract)

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

BMC Public Health. 2019 Nov 14;19(1):1523. doi: 10.1186/s12889-019-7899-2.

The global burden of premature mortality due to the Middle East respiratory syndrome (MERS) using standard expected years of life lost, 2012 to 2019.

Salamatbakhsh M1, Mobaraki K2, Sadeghimohammadi S3, Ahmadzadeh J4.

Author information: 1 MSc of Critical Care Nursing, Urmia University of Medical Sciences, Urmia, Iran. 2 Epidemiologist, Social Determinants of Health Research Center, Urmia University of Medical Sciences, Urmia, Iran. 3 MSc of Critical Care Nursing, School of Nursing and Midwifery, Zanjan University of Medical Sciences, Zanjan, Iran. 4 Epidemiologist, Social Determinants of Health Research Center, Urmia University of Medical Sciences, Urmia, Iran. Ahmadzadeh.j@umsu.ac.ir.

 

Abstract

BACKGROUND:

It has been 8 years since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was reported in Saudi Arabia and the disease is still being reported in 27 countries; however, there is no international study to estimate the overall burden related of this emerging infectious disease. The present study was conducted to assess the burden of premature mortality due to Middle East respiratory syndrome (MERS) worldwide.

METHODS:

In this retrospective analysis, we have utilized publicly available data from the WHO website related to 1789 MERS patients reported between September 23, 2012 and May 17, 2019. To calculate the standard expected years of life lost (SEYLL), life expectancy at birth was set according to the 2000 global burden of disease study on levels 25 and 26 of West model life tables from Coale-Demeny at 82.5 and 80 years for females and males, respectively.

RESULTS:

Overall, the total SEYLL in males and females was 10,702 and 3817.5 years, respectively. The MERS patients within the age range of 30-59 year-olds had the highest SEYLL (8305.5 years) in comparison to the patients within the age groups 0-29 (SEYLL = 3744.5 years) and ≥ 60 years (SEYLL = 2466.5 years). The total SEYLL in all age groups in 2012, 2013, 2014, 2015, 2016, 2017, 2018, and 2019 were 71.5, 2006.5, 3162, 4425.5, 1809.5, 878, 1257.5 and 909 years, respectively. The most SEYLL related to MERS-CoV infection was in the early four years of the onset of the pandemic (2012 to 2015) and in the last four years of the MERS-CoV pandemic (216 to 2019), a significant reduction was observed in the SEYLL related to MERS-CoV infection in the MERS patients.

CONCLUSION:

We believe that the findings of this study will shed light about the burden of premature mortality due to MERS infection in the world and the results may provide necessary information for policy-makers to prevent, control, and make a quick response to the outbreak of MERS-CoV disease.

KEYWORDS: Burden of disease; Premature mortality; Standard expected years of life; Worldwide

PMID: 31727042 DOI: 10.1186/s12889-019-7899-2

Keywords: MERS-CoV.

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Complete #Genome #Sequence of a #Colombian #Zika Virus Strain Obtained from BALB/c Mouse #Brain after Intraperitoneal Inoculation (Microbiol Resourc Announc., abstract)

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

Microbiol Resour Announc. 2019 Nov 14;8(46). pii: e01719-18. doi: 10.1128/MRA.01719-18.

Complete Genome Sequence of a Colombian Zika Virus Strain Obtained from BALB/c Mouse Brain after Intraperitoneal Inoculation.

Laiton-Donato K1, Álvarez-Díaz DA2, Rengifo AC3, Torres-Fernández O2, Usme-Ciro JA1,4, Rivera JA2, Santamaría G2, Naizaque J2, Monroy-Gómez J2,5, Sarmiento L2, Gunturiz ML6, Muñoz A7, Vanegas R7, Rico A1, Pardo L1, Peláez-Carvajal D1.

Author information: 1 Grupo de Virología, Dirección de Redes en Salud Pública, Instituto Nacional de Salud, Bogotá, DC, Colombia. 2 Grupo de Morfología Celular, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, DC, Colombia. 3 Grupo de Morfología Celular, Dirección de Investigación en Salud Pública, Instituto Nacional de Salud, Bogotá, DC, Colombia arengifo@ins.gov.co. 4 Centro de Investigación en Salud para el Trópico-CIST, Universidad Cooperativa de Colombia, Santa Marta, Colombia. 5 Escuela Colombiana de Rehabilitación, Bogotá, DC, Colombia. 6 Equipo Banco de Proyectos, Dirección de Investigación en Salud Pública, Bogotá, DC, Colombia. 7 Grupo Animales de Laboratorio, Dirección de Producción, Instituto Nacional de Salud, Bogotá, DC, Colombia.

 

Abstract

A Zika virus (ZIKV) strain was isolated from an acute febrile patient during the Zika epidemics in Colombia. The strain was intraperitoneally inoculated into BALB/c mice, and 7 days postinoculation, neurological manifestations and ZIKV infection in the brain were demonstrated. The reported genome sequence is highly related to strains circulating in the Americas.

Copyright © 2019 Laiton-Donato et al.

PMID: 31727724 DOI: 10.1128/MRA.01719-18

Keywords: Zika Virus; Colombia.

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#Drug #Decriminalization: A Matter of #Justice and #Equity, Not Just Health (Am J Prev Med., abstract)

[Source: American Journal of Preventive Medicine, full page: (LINK). Abstract, edited.]

Drug Decriminalization: A Matter of Justice and Equity, Not Just Health

Hakique N. Virani, MD1, Rebecca J. Haines-Saah, PhD2

DOI: https://doi.org/10.1016/j.amepre.2019.08.012

Published online: November 15, 2019

 

Abstract

Since 2016, more than 10,300 Canadians have died of an apparent opioid-related overdose, with the majority involving fentanyl or fentanyl analogs.1 This unprecedented public health crisis has decreased life expectancy at birth in the country’s most affected provinces of Alberta and British Columbia.2 Concerned by this epidemic of overdoses, Canadian advocates for drug policy reform have welcomed the recent recommendation from British Columbia’s Provincial Health Officer that drug possession for personal use be decriminalized.

© 2019 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Keywords: Opioids; Illicit drugs; Society; Canada.

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