The interrelations of radiologic findings and mechanical ventilation in community acquired pneumonia patients admitted to the intensive care unit: a multicentre retrospective study |
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Authors: | Hakan Erdem Zeliha Kocak-Tufan Omer Yilmaz Zuhal Karakurt Aykut Cilli Hulya Turkan Ozlem Yazicioglu-Mocin Nalan Adıguzel Gokay Gungor Canturk Taşcı Gulden Yilmaz Oral Oncul Aygul Dogan-Celik Ozcan Erdemli Nefise Oztoprak Yakup Tomak Asuman Inan Demet Tok Sibel Temur Hafize Oksuz Ozgur Senturk Unase Buyukkocak Fatma Yilmaz-Karadag Derya Ozturk-Engin Dilek Ozcengiz Ahmet Karakas Hayati Bilgic Hakan Leblebicioglu |
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Institution: | 1. Department of Pathology and Laboratory Medicine, University of British Columbia, 950 W 28th Avenue, Vancouver, British Columbia, V5Z 4H4, Canada 3. Centre for Understanding and Preventing Infection in Children, Child & Family Research Institute, University of British Columbia, 950 W 28th Avenue, Vancouver, British Columbia, V5Z 4H4, Canada 2. Department of Pediatrics, University of British Columbia, 950 W 28th Avenue, Vancouver, British Columbia, V5Z 4H4, Canada
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Abstract: | Background Burkholderia cepacia complex (BCC) bacteria are highly virulent, typically multidrug-resistant, opportunistic pathogens in cystic fibrosis (CF) patients and other immunocompromised individuals. B. vietnamiensis is more often susceptible to aminoglycosides than other BCC species, and strains acquire aminoglycoside resistance during chronic CF infection and under tobramycin and azithromycin exposure in vitro, apparently from gain of antimicrobial efflux as determined through pump inhibition. The aims of the present study were to determine if oxidative stress could also induce aminoglycoside resistance and provide further observations in support of a role for antimicrobial efflux in aminoglycoside resistance in B. vietnamiensis. Findings Here we identified hydrogen peroxide as an additional aminoglycoside resistance inducing agent in B. vietnamiensis. After antibiotic and hydrogen peroxide exposure, isolates accumulated significantly less 3H] gentamicin than the susceptible isolate from which they were derived. Strains that acquired aminoglycoside resistance during infection and after exposure to tobramycin or azithromycin overexpressed a putative resistance-nodulation-division (RND) transporter gene, amrB. Missense mutations in the repressor of amrB, amrR, were identified in isolates that acquired resistance during infection, and not in those generated in vitro. Conclusions These data identify oxidative stress as an inducer of aminoglycoside resistance in B. vietnamiensis and further suggest that active efflux via a RND efflux system impairs aminoglycoside accumulation in clinical B. vietnamiensis strains that have acquired aminoglycoside resistance, and in those exposed to tobramycin and azithromycin, but not hydrogen peroxide, in vitro. Furthermore, the repressor AmrR is likely just one regulator of the putative AmrAB-OprM efflux system in B. vietnamiensis. |
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