Within-host transition to GES-55 during a GES-6-producing Serratia marcescens outbreak: Emergence of ceftazidime-avibactam resistance and increased susceptibility to carbapenems

• Published in: International journal of antimicrobial agents 2024-08, Vol.64 (2), p.107257, Article 107257
• Main Authors: García-Fernández, Sergio, Rodríguez-Grande, Jorge, Siller-Ruiz, María, Fraile-Valcárcel, Nuria, Lara-Plaza, Isabel, Moure, Zaira, Pablo-Marcos, Daniel, Rodríguez-Lozano, Jesús, Suberviola, Borja, Cundín, M. Paz Rodríguez, Fariñas, María Carmen, Ocampo-Sosa, Alain, Calvo-Montes, Jorge
• Format: Article
• Language: English
• Subjects: antibiotic resistance; beta-lactamase; carbapenems; Ceftazidime-avibactam; COVID-19 infection; evolution; genes; GES carbapenemase; mutation; patients; plasmids; retrospective studies; sequence analysis; Serratia marcescens; Spain
• ISSN: 0924-8579; 1872-7913; 1872-7913
• DOI: 10.1016/j.ijantimicag.2024.107257

•Outbreak description of an unusual combination specie-carbapenemase type: blaGES-6S. marcescens.•In vivo emergence of ceftazidime-avibactam resistance and increase of carbapenem susceptibility.•Intra-host evolution of S. marcescens in a relatively short period. To describe the in vivo emergence of ceftazidime-avibactam resistance in GES-type carbapenemases and to characterize an unusual outbreak of GES-6-producing Serratia marcescens during the COVID-19 pandemic in Spain. Retrospective study to describe a GES-CPSM outbreak based on whole genome sequencing and antimicrobial susceptibility testing (AST). Transferability of blaGES-carrying plasmid was assessed by conjugation experiments. In December 2020, we identified a cluster of S. marcescens harbouring blaGES-6 involving 9 patients. Whole-genome sequence analysis revealed a clonal relationship (≤3 SNPs) between the first isolates identified in each of the evolved patients and environmental samples with GES-CPSM detection. Plasmid analysis showed that the blaGES-6 gene was located in an IncQ3-type plasmid. Triparental mating experiments using a helper plasmid demonstrated mobilization of the blaGES-6-carrying plasmid. Our results also demonstrate within-host evolution in S. marcescens isolates, leading to a transition from blaGES-6 to the new blaGES-55, caused by the P162S mutation, in a subsequent infection in one of the affected patients. In blaGES-55 we identified emergence of ceftazidime-avibactam resistance along with an increase of carbapenems susceptibility. This patient had been treated with a 14-day course of ceftazidime-avibactam. AST of the transformants bearing blaGES-6 and blaGES-55 plasmids, confirmed susceptibility variation affecting ceftazidime-avibactam and carbapenems. We report an unusual outbreak of GES-6 whose incidence is becoming increasing. Transition from GES-6 to GES-55 may readily occur in vivo leading to ceftazidime-avibactam resistance, which brings to the fore the critical need for developing more accurate diagnosis tools for detection of GES β–lactamases and optimise the use of antimicrobials.