Archive for May 28, 2017

Rifabutin Is Active against Mycobacterium abscessus Complex

Antimicrob. Agents Chemother. June 2017 V.61 N.6

Dinah Binte Aziz, Jian Liang Low, Mu-Lu Wu, Martin Gengenbacher, Jeanette W. P. Teo, Véronique Dartois, and Thomas Dick

aDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

bDepartment of Laboratory Medicine, National University Hospital, Singapore

cPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, USA

Lung infections caused by Mycobacterium abscessus are emerging as a global threat to individuals with cystic fibrosis and to other patient groups. Recent evidence for human-to-human transmission worsens the situation. M. abscessus is an intrinsically multidrug-resistant pathogen showing resistance to even standard antituberculosis drugs, such as rifampin. Here, our objective was to identify existing drugs that may be employed for the treatment of M. abscessus lung disease. A collection of more than 2,700 approved drugs was screened at a single-point concentration against an M. abscessus clinical isolate. Hits were confirmed with fresh solids in dose-response experiments. For the most attractive hit, growth inhibition and bactericidal activities against reference strains of the three M. abscessus subspecies and a collection of clinical isolates were determined. Surprisingly, the rifampin derivative rifabutin had MICs of 3 ± 2 μM (3 μg/ml) against the screening strain, the reference strains M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii CCUG 50184-T, and M. abscessus subsp. massiliense CCUG 48898-T, as well as against a collection of clinical isolates. Furthermore, rifabutin was active against clarithromycin-resistant strains. In conclusion, rifabutin, in contrast to rifampin, is active against the Mycobacterium abscessus complex bacteria in vitro and may be considered for treatment of M. abscessus lung disease.

PDF

http://aac.asm.org/content/61/6/e00155-17.full.pdf+html

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May 28, 2017 at 4:54 pm

The Race To Find Antivirals for Zika Virus

Antimicrob. Agents Chemother. June 2017 V.61 N.6

Juan-Carlos Saiz and Miguel A. Martín-Acebes

Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain

Zika virus (ZIKV), a flavivirus transmitted by mosquitoes, was an almost neglected pathogen until its introduction in the Americas in 2015 and its subsequent explosive spread throughout the continent, where it has infected millions of people. The virus has caused social and sanitary alarm, mainly due to its association with severe neurological disorders (Guillain-Barré syndrome and microcephaly in fetuses and newborns). Nowadays, no specific antiviral therapy against ZIKV is available. However, during the past months, a great effort has been made to search for antiviral candidates using different approaches and methodologies, ranging from testing specific compounds with known antiviral activity to the screening of libraries with hundreds of bioactive molecules. The identified antiviral candidates include drugs targeting viral components as well as cellular ones. Here, an updated review of what has been done in this line is presented.

PDF

http://aac.asm.org/content/61/6/e00411-17.full.pdf+html

May 28, 2017 at 4:52 pm

Epidemiological and Molecular Characterization of an Invasive Group A Streptococcus emm32.2 Outbreak

J. Clin. Microbiol. June 2017 V.55 N.6

Jennifer E. Cornick, Anmol M. Kiran, Roberto Vivancos, Jon Van Aartsen, Jenny Clarke, Edward Bevan, Mansoor Alsahag, Maaike Alaearts, Laura Bricio Moreno, Howard F. Jenkinson, Angela H. Nobbs, James Anson, Aras Kadiolgu, Neil French, and Dean B. Everett

aMalawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi

bInstitute of Infection & Global Health, University of Liverpool, Liverpool, United Kingdom

cField Epidemiology Service, Public Health England, London, United Kingdom

dNIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom

eHeart of England NHS Foundation Trust, Birmingham Heartlands Hospital, Birmingham, United Kingdom

fSchool of Oral and Dental Sciences, University of Bristol, Bristol, United Kingdom

gLiverpool Clinical Laboratories, Royal Liverpool & Broadgreen University Hospitals Trust, Liverpool, United Kingdom

An emm32.2 invasive group A streptococcus (iGAS) outbreak occurred in Liverpool from January 2010 to September 2012. This genotype had not previously been identified in Liverpool, but was responsible for 32% (14/44) of all iGAS cases reported during this time period. We performed a case-case comparison of emm32.2 iGAS cases with non-emm32.2 control iGAS cases identified in the Liverpool population over the same time period to assess patient risk factors for emm32.2 iGAS infection. The emm32.2 iGAS cases were confined to the adult population. We show that homelessness, intravenous drug use, and alcohol abuse predisposed patients to emm32.2 iGAS disease; however, no obvious epidemiological linkage between the patients with emm32.2 iGAS could be identified. Comparative whole-genome sequencing analysis of emm32.2 iGAS and non-emm32.2 control isolates was also performed to identify pathogen factors which might have driven the outbreak. We identified 19 genes, five of which had previously been implicated in virulence, which were present in all of the emm32.2 iGAS isolates but not present in any of the non-emm32.2 control isolates. We report that a novel emm32.2 genotype emerged in Liverpool in 2010 and identified a specific subset of genes, which could have allowed this novel emm32.2 genotype to persist in a disadvantaged population in the region over a 3-year period.

PDF

http://jcm.asm.org/content/55/6/1837.full.pdf+html

May 28, 2017 at 4:51 pm

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014

Clin. Microbiol. June 2017 V.55 N.6

James A. Karlowsky, Sibylle H. Lob, Krystyna M. Kazmierczak, Robert E. Badal, Katherine Young, Mary R. Motyl, and Daniel F. Sahm

aDepartment of Medical Microbiology, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

bInternational Health Management Associates, Inc., Schaumburg, Illinois, USA

cMerck Sharp & Dohme Corp., Kenilworth, New Jersey, USA

The Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program collected 103,960 isolates of Enterobacteriaceae from 2008 to 2014. From this isolate collection, all ertapenem-nonsusceptible isolates (MIC, ≥1 μg/ml; n = 3,428) and 9,371 isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with an ertapenem-susceptible extended-spectrum-β-lactamase (ESBL)-positive phenotype were assessed for the presence of common carbapenemase genes using a Check-MDR CT101 microarray (Check-Points, Wageningen, the Netherlands) and published multiplex PCR assays. Testing identified 1,493 isolates that harbored a carbapenemase gene (1,485 ertapenem-nonsusceptible isolates and 8 ertapenem-susceptible ESBL-positive isolates) and accounted for 1.4% (1,493/103,960) of all isolates of Enterobacteriaceae. The most frequently identified carbapenemase genes were the KPC (n = 794), OXA-48-like (n = 300), and NDM (n = 290) genes. Carbapenemase genes were most frequently identified in Klebsiella pneumoniae (n = 1,127), Escherichia coli (n = 149), and Enterobacter cloacae (n = 110). Among the carbapenemase-positive isolates, 66.7% (2/3), 37.0% (111/300), 20.0% (8/40), 3.3% (3/92), 2.3% (18/794), and 0% (0/290) of the isolates with genes for GES, OXA-48-like, IMP, VIM, KPC, and NDM, respectively, were susceptible to imipenem (MIC, ≤1 μg/ml). Isolates that tested as susceptible to imipenem were not uncommon among carbapenemase-positive isolates (9.4%, 141/1,493) and most frequently carried OXA-48-like enzymes (78.7%; 111/141); however, overall, these isolates remained rare (0.1%, 141/103,960). The practice of screening clinical isolates of Enterobacteriaceae that test as susceptible to carbapenems in vitro for the presence of carbapenemase genes remains controversial and requires further study.

PDF

http://jcm.asm.org/content/55/6/1638.full.pdf+html

May 28, 2017 at 4:50 pm

Commentary – The Immaculate Carbapenemase Study

Clin. Microbiol. June 2017 V.55 N.6

Kenneth S. Thomson

University of Louisville School of Medicine, Louisville, Kentucky, USA

Carbapenemase-producing organisms, or CPOs, are Gram-negative pathogens that produce a transmissible carbapenemase and are typically resistant to most (sometimes all) antibiotics. We now face a global CPO pandemic of high mortality. In this issue of the Journal of Clinical Microbiology, Karlowsky et al. (J Clin Microbiol 55:1638–1649, 2017, https://doi.org/10.1128/JCM.02316-16) report the results of an extensive global surveillance study that provide much-needed information that enhances our understanding of carbapenemase-producing Enterobacteriaceae (CPE) and which will be valuable for the development of improved strategies for CPE control and therapy of infections.

PDF

http://jcm.asm.org/content/55/6/1608.full.pdf+html

 

May 28, 2017 at 4:48 pm


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