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

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dc.contributor.author Carvajal, Lina P.
dc.contributor.author Rincon, Sandra
dc.contributor.author Echeverri, Aura M.
dc.contributor.author Porras, Jessica
dc.contributor.author Rios, Rafael
dc.contributor.author Ordoñez, Karen M.
dc.contributor.author Seas Ramos, Carlos Rafael
dc.contributor.author Gomez-Villegas, Sara I.
dc.contributor.author Diaz, Lorena
dc.contributor.author Arias, Cesar A.
dc.contributor.author Reyes, Jinnethe
dc.date.accessioned 2020-07-14T00:01:02Z
dc.date.available 2020-07-14T00:01:02Z
dc.date.issued 2020
dc.identifier.uri https://hdl.handle.net/20.500.12866/8257
dc.description.abstract Cefazolin 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. en_US
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.relation.ispartofseries Antimicrobial Agents and Chemotherapy
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject BlaZ allotypes en_US
dc.subject cefazolin en_US
dc.subject inoculum effect en_US
dc.subject MSSA en_US
dc.title Novel insights into the classification of staphylococcal β-lactamases in relation to the cefazolin inoculum effect en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1128/AAC.02511-19
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.05
dc.relation.issn 1098-6596


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