Novel insights into the classification of staphylococcal β-lactamases in relation to the cefazolin inoculum effect

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dc.contributor.authorCarvajal Ortiz, Lina Paola
dc.contributor.authorRincon Núñez, Sandra
dc.contributor.authorEcheverri Medina, Aura María
dc.contributor.authorPORRAS GUZMAN, JESSICA
dc.contributor.authorRios, Rafael
dc.contributor.authorOrdóñez, Karen Melissa
dc.contributor.authorSeas, Carlos
dc.contributor.authorGomez-Villegas, Sara Isabel
dc.contributor.authorDiaz, Lorena
dc.contributor.authorArias, Cesar A
dc.contributor.authorReyes, Jinnethe
dc.contributor.orcidRincon Núñez, Sandra [0000-0002-8482-4554]
dc.contributor.orcidCarvajal Ortiz, Lina Paola [0000-0001-8301-8836]
dc.date.accessioned2020-07-15T17:42:02Z
dc.date.available2020-07-15T17:42:02Z
dc.date.issued2020
dc.description.abstractenglishCefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal β-lactamases. Four variants of staphylococcal β-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal β-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the β-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for β-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant β-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P β <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal β-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1128/aac.02511-19
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1098-6596
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlhttps://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/3499
dc.language.isoeng
dc.publisherAmerican Society for Microbiologyspa
dc.publisher.journalAntimicrobial agents and chemotherapyspa
dc.relation.ispartofseriesAntimicrobial agents and chemotherapy, 1098-6596, Vol. 64, Nro. 5, 2020spa
dc.relation.urihttps://aac.asm.org/content/64/5/e02511-19.long
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2020-05-01
dc.rights.localAcceso abiertospa
dc.subject.armarcCefazolinaspa
dc.subject.decsStaphylococcus aureusspa
dc.subject.decsBeta-Lactamasasspa
dc.subject.decsCefazolinaspa
dc.titleNovel insights into the classification of staphylococcal β-lactamases in relation to the cefazolin inoculum effectspa
dc.title.translatedNovel insights into the classification of staphylococcal β-lactamases in relation to the cefazolin inoculum effectspa
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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