Clonal Spread and Intra- and Inter-Species Plasmid Dissemination Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales During a Hospital Outbreak in Barcelona, Spain.

Marta Marí-Almirall,Ignasi Roca,Irene Campo,Clara Cosgaya,Andrea Vergara,Pilar Ciruela,Álex Soriano,José Antonio Martínez,Laura Muñoz,Cristina Pitart,Francesc Marco,Laura Rodríguez-Serna,Anna Cuscó,Gemina Santana,Joaquim Viñes,Elisa Rubio,Olga Francino,Amadéu Gené ,Yuliya Zboromyrska ,Araceli González-Cuevas ,Martina Pellicé ,C Gallés ,Mariana Fernández ,Ana Del Rı́o ,Miguel Ángel Benítez ,Goretti Sauca ,Mónica Ballestero-Téllez ,Xavier Raga ,Frederic Gómez Ester Picó ,Isabel Pujol ,Iolanda Calvet ,Frédéric Ballester ,María Izquierdo Pulido ,Jordi Vilà ,Emma Padilla ,Anna Vilamala ,Pepa Pérez Jove ,Raquel Clivillé ,Carolina Sarvisé ,Joan Lopez Madueño ,Sara González ,N D Juan Ferrando ,Carmina Martí-Sala ,Glòria Trujillo ,Xesca Font

doi:10.3389/fmicb.2021.781127

Abstract

Objectives: The study aimed to characterize the clonal spread of resistant bacteria and dissemination of resistance plasmids among carbapenem-resistant Enterobacterales at a tertiary hospital in Catalonia, Spain.Methods: Isolates were recovered from surveillance rectal swabs and diagnostic samples. Species identification was by matrix-assisted laser desorption ionization-time time of flight mass spectrometry (MALDI-TOF MS). Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Antimicrobial susceptibility was assessed by gradient-diffusion and carriage of bla genes was detected by PCR. Plasmid typing, conjugation assays, S1-PFGE studies and long-read sequencing were used to characterize resistance plasmids.Results: From July 2018 to February 2019, 125 Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales were recovered from 101 inpatients from surveillance (74.4%) or clinical samples (25.6%), in a tertiary hospital in Barcelona. Clonality studies identified a major clone of Klebsiella pneumoniae belonging to sequence type ST15 and additional isolates of K. pneumoniae, Escherichia coli and Enterobacter sp. from different STs. All isolates but one carried the blaKPC–2 allelic variant. The blaKPC–2 gene was located in an IncFIIk plasmid of circa 106 Kb in a non-classical Tn4401 element designated NTEKPC-pMC-2-1. Whole-genome sequencing revealed different rearrangements of the 106 Kb plasmid while the NTEKPC-pMC-2-1 module was highly conserved.Conclusion: We report a hospital outbreak caused by the clonal dissemination of KPC-producing ST15 K. pneumoniae but also the intra- and inter-species transmission of the blaKPC–2 gene associated with plasmid conjugation and/or transposon dissemination. To our knowledge, this is the first report of an outbreak caused by KPC-producing Enterobacterales isolated from human patients in Catalonia and highlights the relevance of surveillance studies in the early detection and control of antibiotic resistant high-risk clones.

Highlights

The rapid emergence of bacterial pathogens presenting resistance to multiple antimicrobial agents (MDR) together with the decreasing trend in the development of new antimicrobial compounds constitute an extremely serious threat to public health (Roca et al, 2015)
Organizations such as the US Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) are considering infections caused by MDR bacteria as an emergent global disease and a major public health problem (Roca et al, 2015)
Klebsiella pneumoniae carbapenemase (KPC)-2 and KPC-3-producing Enterobacterales were later reported in the central region of Spain and Andalusia mainly associated with K. pneumoniae isolates belonging to the CG258 or ST101 (López-Cerero et al, 2014; Porres-Osante et al, 2014; Oteo et al, 2016)

Summary

Introduction

The rapid emergence of bacterial pathogens presenting resistance to multiple antimicrobial agents (MDR) together with the decreasing trend in the development of new antimicrobial compounds constitute an extremely serious threat to public health (Roca et al, 2015). The same report estimated that this figure would rise to 10 million annual deaths by 2050 unless there is a global effort to tackle AMR Likewise, organizations such as the US Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) are considering infections caused by MDR bacteria as an emergent global disease and a major public health problem (Roca et al, 2015). Organizations such as the US Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) are considering infections caused by MDR bacteria as an emergent global disease and a major public health problem (Roca et al, 2015) According to their mortality, health-care and community burden, prevalence of resistance and treatability, carbapenem-resistant Enterobacterales have been included into the 2017 WHO priority list of antibiotic-resistant bacterial pathogens and currently constitute one of the major public health threats worldwide (Tacconelli et al, 2017)

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