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

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.

• Autores: Carvajal Ortiz, Lina Paola; Rincon Núñez, Sandra; Echeverri Medina, Aura María; PORRAS GUZMAN, JESSICA; Rios, Rafael; Ordóñez, Karen Melissa; Seas, Carlos; Gomez-Villegas, Sara Isabel; Diaz, Lorena; Arias, Cesar A; Reyes, Jinnethe
• Tipo de recurso: https://purl.org/coar/resource_type/c_6501
• Fecha de publicación: 2020
• Institución: Universidad El Bosque
• Repositorio: Repositorio U. El Bosque
• Idioma: eng
• OAI Identifier: oai:repositorio.unbosque.edu.co:20.500.12495/3499
• Acceso en línea: https://hdl.handle.net/20.500.12495/3499; https://doi.org/10.1128/aac.02511-19; https://repositorio.unbosque.edu.co
• Palabra clave: Staphylococcus aureus; Beta-Lactamasas; Cefazolina; Cefazolina
• License: Acceso abierto