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 A.
dc.contributor.authorKim, Jiwoong
dc.contributor.authorMunita, Jose M.
dc.contributor.authorSahasrabhojane, Pranoti V.
dc.contributor.authorShields, Ryan K.
dc.contributor.authorPress, Ellen G.
dc.contributor.authorLi, Xiqi
dc.contributor.authorArias, César A.
dc.contributor.authorCantarel, Brandi L.
dc.contributor.authorJiang, Ying
dc.contributor.authorKim, Min S .
dc.contributor.authorAitken, Samuel
dc.contributor.authorGreenberg, David
dc.date.accessioned2020-07-15T22:53:51Z
dc.date.available2020-07-15T22:53:51Z
dc.description.abstractenglishBackground 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 4 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 4 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 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, and positive and negative predictive values for WGS in predicting AMR were 0.87, 0.98, 0.97, and 0.91, respectively. Using BMD 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 = .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.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1093/cid/cix417
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1537-6591
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlhttps://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/3517
dc.language.isoeng
dc.publisherOxford University Pressspa
dc.publisher.journalClinical infectious diseasesspa
dc.relation.ispartofseriesClinical infectious diseases, 1537-6591, Vol. 65, Nro. 5. 2017, p. 738-745spa
dc.relation.urihttps://academic.oup.com/cid/article/65/5/738/3792170
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2017-05-03
dc.rights.localAcceso abiertospa
dc.subject.decsADN Polimerasa dirigida por ADNspa
dc.subject.decsSecuenciación completa del genomaspa
dc.subject.decsPruebas de sensibilidad microbianaspa
dc.subject.keywordsAntimicrobial resistancespa
dc.subject.keywordsWhole-genome sequencingspa
dc.subject.keywordsGram-negative bacteriaspa
dc.titleWhole-genome sequencing accurately identifies resistance to extended-spectrum β-lactams for major gram-negative bacterial pathogensspa
dc.title.translatedWhole-genome sequencing accurately identifies resistance to extended-spectrum β-lactams for major gram-negative bacterial pathogensspa
dc.type.coarhttps://purl.org/coar/resource_type/c_6501
dc.type.driverinfo:eu-repo/semantics/article
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localArtículo de revista

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