Archive for July 5, 2017

Correcting a Fundamental Flaw in the Paradigm for Antimicrobial Susceptibility Testing.

EBioMedicine. 2017 Jun;20:173-181.

Ersoy SC1, Heithoff DM2, Barnes L 5th1, Tripp GK1, House JK3, Marth JD4, Smith JW5, Mahan MJ6.

Author information

1 Dept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.

2 Dept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA; Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA.

3 University of Sydney, Faculty of Veterinary Science, Camden, New South Wales, Australia.

4 Dept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA; Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA; Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA 92037, USA.

5 Sanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA 92037, USA.

6 Dept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA; Center for Nanomedicine, University of California, Santa Barbara, CA 93106, USA. Electronic address: michael.mahan@lifesci.ucsb.edu

Abstract

The emergence and prevalence of antibiotic-resistant bacteria are an increasing cause of death worldwide, resulting in a global ‘call to action’ to avoid receding into an era lacking effective antibiotics.

Despite the urgency, the healthcare industry still relies on a single in vitro bioassay to determine antibiotic efficacy. This assay fails to incorporate environmental factors normally present during host-pathogen interactions in vivo that significantly impact antibiotic efficacy.

Here we report that standard antimicrobial susceptibility testing (AST) failed to detect antibiotics that are in fact effective in vivo; and frequently identified antibiotics that were instead ineffective as further confirmed in mouse models of infection and sepsis.

Notably, AST performed in media mimicking host environments succeeded in identifying specific antibiotics that were effective in bacterial clearance and host survival, even though these same antibiotics failed in results using standard test media.

Similarly, our revised media further identified antibiotics that were ineffective in vivo despite passing the AST standard for clinical use.

Supplementation of AST medium with sodium bicarbonate, an abundant in vivo molecule that stimulates global changes in bacterial structure and gene expression, was found to be an important factor improving the predictive value of AST in the assignment of appropriate therapy.

These findings have the potential to improve the means by which antibiotics are developed, tested, and prescribed.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478264/pdf/main.pdf

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July 5, 2017 at 10:26 pm

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia

Journal of Infectious Diseases May 15, 2017 V.215 N.10 P.1514-1522

EDITOR’S CHOICE

Michael Boeckh  Terry Stevens-Ayers  Giovanna Travi  Meei-Li Huang  Guang-Shing Cheng Hu Xie  Wendy Leisenring  Veronique Erard  Sachiko Seo  Louise Kimball  …

Background.

Quantitative cytomegalovirus (CMV) DNA–specific polymerase chain reaction (PCR) analysis is widely used as a surveillance method for hematopoietic stem cell transplant (HCT) recipients. However, no CMV DNA threshold exists in bronchoalveolar lavage (BAL) to differentiate pneumonia from pulmonary shedding.

Methods.

We tested archived BAL fluid samples from 132 HCT recipients with CMV pneumonia and 139 controls (100 patients with non-CMV pneumonia, 18 with idiopathic pneumonia syndrome [IPS], and 21 who were asymptomatic) by quantitative CMV and β-globin DNA–specific PCR.

Results.

Patients with CMV pneumonia had higher median viral loads (3.9 log10 IU/mL; interquartile range [IQR], 2.6–6.0 log10 IU/mL) than controls (0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with non-CMV pneumonia, 0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with IPS, and 1.63 log10 IU/mL [IQR, 0–2.5 log10 IU/mL] for patients who were asymptomatic; P < .001 for all comparisons to patients with CMV pneumonia). Receiver operating characteristic curve analyses and predictive models identified a cutoff CMV DNA level of 500 IU/mL to differentiate between CMV pneumonia and pulmonary shedding, using current CMV pneumonia prevalence figures. However, different levels may be appropriate in settings of very high or low CMV pneumonia prevalence. The presence of pulmonary copathogens, radiographic presentation, or pulmonary hemorrhage did not alter predictive values.

Conclusion.

CMV DNA load in BAL can be used to differentiate CMV pneumonia from pulmonary shedding.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jid/215/10/10.1093_infdis_jix048/3/jix048.pdf?Expires=1499397143&Signature=ZGqgqbQ9a2uE12bomeqsVGChCW1Y3N54DapASFYI-SwrBn~eaUCXlNiXdKohVR-mw9Lx4NsjrxxqpIuvbiiGy8rpCb0sOLHdUlt8eA-mB7oZe249GgBvS8Oz9pXG-D7qBtEJ3jMI235GXMaYneGNv50wGHU6Nu3jzmffhXrz9GqjXrO5u80MlMtQDeB3DtOQVMl5vF4~dLL4o~OSWN4hI6gwqaR998s1l5iSspqNsU4suq4TmFlwcNLrmBpSA8z8XRVsKsS~7RrBDsGENU5SDxXp1AZmY50mHB3fvKjpnLXPdvQdedi3wHLfereEU5i7PaZ3MBlPz-RvtbGiMXjMUA__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

July 5, 2017 at 10:24 pm


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