Dataset Information

Assessing the role of inter-facility patient transfer in the spread of carbapenemase-producing Enterobacteriaceae: the case of France between 2012 and 2015.

ABSTRACT: The spread of carbapenemase-producing Enterobacteriaceae (CPE) in healthcare settings is a major public health threat that has been associated with cross-border and local patient transfers between healthcare facilities. Since the impact of transfers on spread may vary, our study aimed to assess the contribution of a patient transfer network on CPE incidence and spread at a countrywide level, with a case study of France from 2012 to 2015. Our results suggest a transition in 2013 from a CPE epidemic sustained by internationally imported episodes to an epidemic sustained by local transmission events through patient transfers. Incident episodes tend to occur within close spatial distance of their potential infector. We also observe an increasing frequency of multiple spreading events, originating from a limited number of regional hubs. Consequently, coordinated prevention and infection control strategies should focus on transfers of carriers of CPE to reduce regional and inter-regional transmission.

SUBMITTER: Nekkab N

PROVIDER: S-EPMC7483561 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Assessing the role of inter-facility patient transfer in the spread of carbapenemase-producing Enterobacteriaceae: the case of France between 2012 and 2015.

Nekkab Narimane N Crépey Pascal P Astagneau Pascal P Opatowski Lulla L Temime Laura L

Scientific reports 20200910 1

The spread of carbapenemase-producing Enterobacteriaceae (CPE) in healthcare settings is a major public health threat that has been associated with cross-border and local patient transfers between healthcare facilities. Since the impact of transfers on spread may vary, our study aimed to assess the contribution of a patient transfer network on CPE incidence and spread at a countrywide level, with a case study of France from 2012 to 2015. Our results suggest a transition in 2013 from a CPE epidem ...[more]

PMID: 32913244

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Project description:Carbapenemase-producing Escherichia coli (CP-Ec) represents a major public health threat with a risk of dissemination in the community as has occurred for lineages producing extended-spectrum β-lactamases. To characterize the extent of CP-Ec spread in France, isolates from screening and infection samples received at the French National Reference Center (F-NRC) laboratory for carbapenemase-producing Enterobacterales were investigated. A total of 691 CP-Ec isolates collected between 2012 and 2015 and 22 isolates collected before 2012 were fully sequenced. Analysis of their genome sequences revealed some disseminating multidrug-resistant (MDR) lineages frequently acquiring diverse carbapenemase genes mainly belonging to clonal complex 23 (CC23) (sequence type 410 [ST410]) and CC10 (ST10 and ST167) and sporadic isolates, including rare ST131 isolates (n = 17). However, the most represented sequence type (ST) was ST38 (n = 92) with four disseminated lineages carrying blaOXA-48-like genes inserted in the chromosome. Globally, the most frequent carbapenemase gene (n = 457) was blaOXA-48. It was also less frequently associated with MDR isolates being the only resistance gene in 119 isolates. Thus, outside the ST38 clades, its acquisition was frequently sporadic with no sign of dissemination, reflecting the circulation of the IncL plasmid pOXA-48 in France and its high frequency of conjugation. In contrast, blaOXA-181 and blaNDM genes were often associated with the evolution of MDR E. coli lineages characterized by mutations in ftsI and ompC. IMPORTANCE Carbapenemase-producing Escherichia coli (CP-Ec) might be difficult to detect, as MICs can be very low. However, their absolute number and their proportion among carbapenem-resistant Enterobacterales have been increasing, as reported by WHO and national surveillance programs. This suggests a still largely uncharacterized community spread of these isolates. Here, we have characterized the diversity and evolution of CP-Ec isolated in France before 2016. We show that carbapenemase genes are associated with a wide variety of E. coli genomic backgrounds and a small number of dominant phylogenetic lineages. In a significant proportion of CP-Ec, the most frequent carbapenemase gene blaOXA-48, was detected in isolates lacking any other resistance gene, reflecting the dissemination of pOXA-48 plasmids, likely in the absence of any antibiotic pressure. In contrast, carbapenemase gene transfer may also occur in multidrug-resistant E. coli, ultimately giving rise to at-risk lineages encoding carbapenemases with a high potential of dissemination.

Project description:BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) are responsible for worldwide outbreaks and antibiotic treatments are problematic. The polysaccharide poly-(?-1,6)-N-acetyl glucosamine (PNAG) is a vaccine target detected on the surface of numerous pathogenic bacteria, including Escherichia coli. Genes encoding PNAG biosynthetic proteins have been identified in two other main pathogenic Enterobacteriaceae, Enterobacter cloacae and Klebsiella pneumoniae. We hypothesized that antibodies to PNAG might be a new therapeutic option for the different pan-resistant pathogenic species of CRE.MethodsPNAG production was detected by confocal microscopy and its role in the formation of the biofilm (for E. cloacae) and as a virulence factor (for K. pneumoniae) was analysed. The in vitro (opsonophagocytosis killing assay) and in vivo (mouse models of peritonitis) activity of antibodies to PNAG were studied using antibiotic-susceptible and -resistant E. coli, E. cloacae and K. pneumoniae. A PNAG-producing strain of Pseudomonas aeruginosa, an organism that does not naturally produce this antigen, was constructed by adding the pga locus to a strain with inactive alg genes responsible for the production of P. aeruginosa alginate. Antibodies to PNAG were tested in vitro and in vivo as above.ResultsPNAG is a major component of the E. cloacae biofilm and a virulence factor for K. pneumoniae. Antibodies to PNAG mediated in vitro killing (>50%) and significantly protected mice against the New Delhi metallo-?-lactamase-producing E. coli (P?=?0.02), E. cloacae (P?=?0.0196) and K. pneumoniae (P?=?0.006), against K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (P?=?0.02) and against PNAG-producing P. aeruginosa (P?=?0.0013). Thus, regardless of the Gram-negative bacterial species, PNAG expression is the sole determinant of the protective efficacy of antibodies to this antigen.ConclusionsOur findings suggest antibodies to PNAG may provide extended-spectrum antibacterial protective activity.

Dataset Information

Assessing the role of inter-facility patient transfer in the spread of carbapenemase-producing Enterobacteriaceae: the case of France between 2012 and 2015.

Publications

Assessing the role of inter-facility patient transfer in the spread of carbapenemase-producing Enterobacteriaceae: the case of France between 2012 and 2015.

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