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The interrelations of radiologic findings and mechanical ventilation in community acquired pneumonia patients admitted to the intensive care unit: a multicentre retrospective study
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
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
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.
Keywords:
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