{Reference Type}: Journal Article
{Title}: Within-host transition to GES-55 during a GES-6-producing Serratia marcescens outbreak: Emergence of ceftazidime-avibactam resistance and increased susceptibility to carbapenems.
{Author}: García-Fernández S;Rodríguez-Grande J;Siller-Ruiz M;Fraile-Valcárcel N;Lara-Plaza I;Moure Z;Pablo-Marcos D;Rodríguez-Lozano J;Suberviola B;Cundín MPR;Fariñas MC;Ocampo-Sosa A;Calvo-Montes J;
{Journal}: Int J Antimicrob Agents
{Volume}: 64
{Issue}: 2
{Year}: 2024 Aug 23
{Factor}: 15.441
{DOI}: 10.1016/j.ijantimicag.2024.107257
{Abstract}: <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.