AUTHOR=Hadjadj Linda , Cassir Nadim , Saïdani Nadia , Hoffman Clémence , Brouqui Philippe , Astoul Philippe , Rolain Jean-Marc , Baron Sophie Alexandra 

TITLE=Outbreak of carbapenem-resistant enterobacteria in a thoracic-oncology unit through clonal and plasmid-mediated transmission of the blaOXA-48 gene in Southern France

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1048516

DOI=10.3389/fcimb.2022.1048516

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>Carbapenemase-producing <italic>Enterobacteriaceae</italic> (CPE) represent an increasing threat to public health, especially in hospitals.</p></sec><sec><title>Objectives</title><p>To investigate an outbreak of CPE in a thoracic-oncology unit by using whole genome sequencing (WGS) and to describe the control measures taken to limit the epidemic, including fecal microbiota transplantation (FMT).</p></sec><sec><title>Methods</title><p>A retrospective study between December 2016 and October 2017 was performed to investigate an outbreak of CPE in a thoracic-oncology unit at the North Hospital in Marseille, France. The isolates were identified, and antimicrobial susceptibility tests were performed. All CPE were sequenced using MiSeq and/or MinIon technologies. Nucleotide variations between plasmids and similarity within the same species were investigated. The origin of this outbreak, its spread, and the decolonization of patients in the ward were also studied.</p></sec><sec><title>Results</title><p>Four <italic>Citrobacter freundii</italic>, one <italic>Enterobacter cloacae</italic> and four <italic>E. hormaechei</italic> OXA-48 carbapenemase producers were isolated in eight patients hospitalized the same year in a thoracic-oncology ward. The <italic>bla</italic><sub>OXA-48</sub> gene was present in a Tn<italic>1999.2</italic> transposon located in IncL/M plasmids, with single nucleotide variants (SNV) ranging from 0 to 5. All <italic>C. freundii</italic> strains belonged to the same ST22 and had more than 99.6% similarity between them. Two strains of <italic>E. hormaechei</italic> ST1007 were almost identical at 99.98%, while the others belonged to a different ST (ST98, ST114, ST133). No single source was identified. FMT resulted in decolonization in 4/6 patients.</p></sec><sec><title>Conclusions</title><p>WGS demonstrated the dissemination of the <italic>bla</italic><sub>OXA-48</sub> gene by both clonal (<italic>C. freundii</italic> ST22 and <italic>E. hormaechei</italic> ST1007) and plasmid spread (pOXA-48 IncL/M). The origin of this outbreak appeared to be both external and internal to the ward. This evidence of cross-infection supports the urgent need for the implementation of infection control measures to prevent CPE dissemination.</p></sec>