Whole genome sequencing accurately identifies resistance to extended spectrum β-lactams for major gram-negative bacterial pathogens

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dc.contributor.authorShelburne, Samuel
dc.contributor.authorKim, Jiwoong
dc.contributor.authorMunita, José
dc.contributor.authorSahasrabhojane, Pranoti
dc.contributor.authorShields, Ryan
dc.contributor.authorPress, Ellen G
dc.contributor.authorLi, Xiqi
dc.contributor.authorArias, Cesar
dc.contributor.authorCantarel, Brandi
dc.contributor.authorJiang, Ying
dc.contributor.authorKim, Min
dc.contributor.authorAitken, Samuel L.
dc.contributor.authorGreenberg, David
dc.date.accessioned2017-08-29T18:41:42Z
dc.date.available2017-08-29T18:41:42Z
dc.date.issued2017
dc.description.abstractBACKGROUND: There is marked interest in using DNA based methods to detect antimicrobial resistance (AMR) with targeted polymerase chain reaction (PCR) approaches increasingly being incorporated into clinical care. Whole genome sequencing (WGS) could offer significant advantages over targeted PCR for AMR detection, particularly for species where mutations are major drivers of AMR. METHODS: Illumina MiSeq WGS and broth microdilution (BMD) assays were performed on 90 bloodstream isolates of the four most common gram-negative bacteria causing bloodstream infections in neutropenic patients. The WGS data, including both gene presence/absence and detection of mutations in an array of AMR relevant genes, were used to predict resistance to four β-lactams commonly used in the empiric treatment of neutropenic fever. The genotypic predictions were then compared to phenotypic resistance as determined by BMD and by commercial methods during routine patient care. RESULTS: Out of 133 putative instances of resistance to the β-lactams of interest identified by WGS, only 87 (65%) would have been detected by a typical PCR based approach. The sensitivity, specificity, positive and negative predictive values for WGS in predicting AMR were 0.87, 0.98, 0.97, and 0.91 respectively. Using broth microdilution as the gold standard, our genotypic resistance prediction approach had a significantly higher positive predictive value compared to minimum inhibitory concentrations generated by commercial methods (0.97 vs. 0.92, P = 0.025). CONCLUSIONS: These data demonstrate the potential feasibility of using WGS to guide antibiotic treatment decisions for patients with life-threatening infections for an array of medically important pathogens.
dc.description.versionVersión Publicada
dc.format.extent30 p.
dc.identifier.citationShelburne SA, Kim J, Munita JM, Sahasrabhojane P, Shields RK, Press EG, Li X, Arias CA, Cantarel B, Jiang Y, Kim MS, Aitken SL, Greenberg DE. Whole-Genome Sequencing Accurately Identifies Resistance to Extended-Spectrum β-Lactams for Major Gram-Negative Bacterial Pathogens. Clin Infect Dis. 2017 Sep 1;65(5):738-745. doi: 10.1093/cid/cix417.
dc.identifier.urihttp://hdl.handle.net/11447/1616
dc.identifier.urihttp://dx.doi.org/10.1093/cid/cix417
dc.language.isoen_US
dc.publisherOxford University Press
dc.sourceClinical Infectious Diseases
dc.subjectantimicrobial resistance
dc.subjectbacteremia
dc.subjectgram-negative bacteria
dc.subjectneutropenic fever
dc.subjectwhole genome sequencing
dc.titleWhole genome sequencing accurately identifies resistance to extended spectrum β-lactams for major gram-negative bacterial pathogens
dc.typeArtículo

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