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

Fecha de publicación: 01/01/2020 Fecha Ahead of Print: 21/04/2020

Autores organización

Lina Paola Carvajal Ortiz

Autor
Sandra Liliana Rincon Nuñez

Autor
Andres Enrique Matute Echeverri

Autor
Jinnethe Cristina Reyes Manrique

Autor

Autores

Porras J
Rios R
Ordoñez KM
Seas C
Gomez-Villegas SI
Diaz L
Arias CA

Grupos de investigación

Unidad de Genética y Resistencia Antimicrobiana UGRA

Resumen

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 ß-lactamases. Four variants of staphylococcal ß-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal ß-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 ß-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for ß-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 ß-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 ß <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal ß-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE. Copyright © 2020 American Society for Microbiology. All Rights Reserved.

Datos de la publicación

ISSN/ISSNe:: 0066-4804, 1098-6596
Tipo:: Article
Páginas:: -
DOI:: 10.1128/AAC.02511-19
Enlace a otro recurso:: www.scopus.com

Documentos

No hay documentos

Métricas

Filiaciones

Carvajal LP:: Universidad. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia
Rincon S:: Universidad. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia
Echeverri AM:: Universidad. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia
Porras J:: Universidad. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia
Rios R:: Universidad. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia
Ordoñez KM:: E.S.E. Hospital Universitario San Jorge de Pereira, Risaralda, Colombia
Seas C:: Hospital Cayetano Heredia, Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
Gomez-Villegas SI:: Center for Antimicrobial Resistance and Microbial Genomics, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States
Diaz L:: Universidad. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia
Arias CA:: Universidad. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia

Center for Antimicrobial Resistance and Microbial Genomics, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States

Division of Infectious Diseases, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States

Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States

Center for Infectious Diseases, School of Public Health, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States
Reyes J:: Universidad. Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia

Keywords

Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefazolin; Drug Resistance, Bacterial; Humans; Latin America; Microbial Sensitivity Tests; Molecular Epidemiology; Phylogeny; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Whole Genome Sequencing; beta lactamase; cefazolin; antiinfective agent; beta lactamase; beta-lactamase CMY-2; cefazolin; allotype; amino acid substitution; Article; bacterium isolate; bloodstream infection; classification; controlled study; inoculation; methicillin susceptible Staphylococcus aureus; methicillin susceptible Staphylococcus aureus infection; MIC50; MIC90; nonhuman; phylogenetic tree; priority journal; South and Central America; antibiotic resistance; bacteremia; drug effect; enzymology; genetics; human; microbial sensitivity test; microbiology; molecular epidemiology; phylogeny; prevalence; Staphylococcus aureus; Staphylococcus infection; whole genome sequencing