Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals

Autores organización

• Maria Fernanda Mojica Medina

  Autor

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  Elsa Piedad De La Cadena Vivas

  Autor

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  Juan Carlos Garcia Betancur

  Autor

• 

  Christian Jose Pallares Gutierrez

  Autor

• 

  Maria Virginia Villegas Botero

  Autor

Autores

• Porras J
• Novoa-Caicedo I
• Páez-Zamora L
• Appel TM
• Radice MA
• Castañeda-Méndez P
• Gales AC
• Munita JM

Grupos de investigación

• Grupo de Investigación en Resistencia Antimicrobiana y Epidemiología Hospitalaria RAEH

  

  Investigador

  Maria Virginia Villegas Botero

Resumen

Ceftazidime-avibactam (CZA) is the combination of a third-generation cephalosporin and a new non-b-lactam b-lactamase inhibitor capable of inactivating class A, C, and some D b-lactamases. From a collection of 2,727 clinical isolates of Enterobacterales (n = 2,235) and P. aeruginosa (n = 492) that were collected between 2016 and 2017 from five Latin American countries, we investigated the molecular resistance mechanisms to CZA of 127 (18/2,235 [0.8%] Enterobacterales and 109/492 [22.1%] P. aeruginosa). First, by qPCR for the presence of genes encoding KPC, NDM, VIM, IMP, OXA-48-like, and SPM-1 carbapenemases, and second, by whole-genome sequencing (WGS). From the CZA-resistant isolates, MBL-encoding genes were detected in all 18 Enterobacterales and 42/109 P. aeruginosa isolates, explaining their resistant phenotype. Resistant isolates that yielded a negative qPCR result for any of the MBL encoding genes were subjected to WGS. The WGS analysis of the 67 remaining P. aeruginosa isolates showed mutations in genes previously associated with reduced susceptibility to CZA, such as those involved in the MexAB-OprM efflux pump and AmpC (PDC) hyperproduction, PoxB (blaOXA-50-like), FtsI (PBP3), DacB (PBP4), and OprD. The results presented here offer a snapshot of the molecular epidemiological landscape for CZA resistance before the introduction of this antibiotic into the Latin American market. Therefore, these results serve as a valuable comparison tool to trace the evolution of the resistance to CZA in this carbapenemase-endemic geographical region. © 2023 Mojica et al.

Keywords

• Anti-Bacterial Agents; Ceftazidime; Hospitals; Humans; Latin America; Pseudomonas aeruginosa; Pseudomonas Infections; avibactam plus ceftazidime; antiinfective agent; avibactam; avibactam, ceftazidime drug combination; ceftazidime; amino acid substitution; AmpC gene; antibiotic resistance; antibiotic sensitivity; Article; bacterial gene; bacterium isolate; blaGES 19 gene; blaKPC 2 gene; blaOXA 2 gene; DacB gene; DNA extraction; Enterobacter aerogenes; Enterobacter cloacae; Enterobacterales; Escherichia coli; frameshift mutation; gene mutation; Klebsiella pneumoniae; MIC50; MIC90; multilocus sequence typing; nonhuman; OprD gene; phenotype; PoxB gene; Pseudomonas aeruginosa; real time polymerase chain reaction; sequence analysis; Serratia marcescens; whole genome sequencing; hospital; human; Pseudomonas aeruginosa; Pseudomonas infection; South and Central America