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 |
|