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Outbreak of OXA-48-producing Enterobacterales in a haematological ward associated with an uncommon environmental reservoir, France, 2016 to 2019.

ABSTRACT: The hospital water environment, including the wastewater drainage system, is increasingly reported as a potential reservoir for carbapenemase-producing Enterobacterales (CPE). We investigated a persistent outbreak of OXA-48 CPE (primarily Citrobacter freundii) in a haematological ward of a French teaching hospital by epidemiological, microbiological and environmental methods. Between January 2016 and June 2019, we detected 37 new OXA-48 CPE-colonised and/or ‑infected patients in the haematological ward. In October 2017, a unit dedicated to CPE-colonised and/or ‑infected patients was created. Eleven additional sporadic acquisitions were identified after this date without any obvious epidemiological link between patients, except in one case. Environmental investigations of the haematological ward (June-August 2018) identified seven of 74 toilets and one of 39 drains positive for OXA-48 CPE (seven C. freundii, one Enterobacter sakazakii, one Escherichia coli). Whole genome comparisons identified a clonal dissemination of OXA-48-producing C. freundii from the hospital environment to patients. In addition to strict routine infection control measures, an intensive cleaning programme was performed (descaling and bleaching) and all toilet bowls and tanks were changed. These additional measures helped to contain the outbreak. This study highlights that toilets can be a possible source of transmission of OXA-48 CPE.

SUBMITTER: Jolivet S

PROVIDER: S-EPMC8161731 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Social network and genomic analysis of an OXA-48 carbapenemase-producing Enterobacterales hospital ward outbreak in Ireland, 2018-2019.

Project description:BackgroundNosocomial transmission and outbreaks of carbapenemase-producing Enterobacterales (CPE) represent a challenge to healthcare systems. In July 2018, a CPE hospital ward outbreak was declared. Our aim was to investigate transmission patterns, using social network analysis and genomics in a nosocomial CPE outbreak.MethodsA retrospective descriptive analysis of all patients (cases and contacts) admitted to a ward experiencing a CPE outbreak (2018-2019) was undertaken. A case had a negative CPE admission screen, and subsequent positive test. A contact shared a multi-bed area and/or facility with a case (>4 hours). Social networks, including genomics data and ward locations, were constructed. Network metrics were analysed.FindingsForty-five cases and 844 contacts were analysed. The median age of cases was 78 years (IQR 67-83), 58% (n=26) were male and 100% had co-morbidities. The median outbreak ward length-of-stay (LOS) was 17 days (IQR 10-34). OXA-48 CPE was confirmed in all cases and from 26 environmental samples. Social networks identified clusters by time, gender and species/sequence type/plasmid. Network metrics indicated potential superspreading involving a subset of patients with behavioural issues.ConclusionSocial networks elucidated high resolution transmission patterns involving two related OXA-48 plasmids, multiple species/genotypes and potential super-spreading. Interventions prevented intra-hospital spread. An older patient cohort, extended hospital LOS and frequent intra-ward bed transfers, coupled with suboptimal ward infrastructure, likely prolonged this outbreak. We recommend social network analysis contemporaneously with genomics (on case and environmental samples) for complex nosocomial outbreaks and bespoke care plans for patients with behavioural issues on outbreak wards.

| S-EPMC10164899 | biostudies-literature

Molecular epidemiology of an extended multiple-species OXA-48 CPE outbreak in a hospital ward in Ireland, 2018-2019.

Project description:ObjectivesMolecular epidemiological description of an OXA-48 CPE outbreak affecting a tertiary-care hospital ward in Ireland over an extended period (2018-2019).MethodsMicrobiological testing and whole-genome sequencing (WGS) were performed on all 56 positive OXA-48 outbreak case isolates.ResultsIn total, 7 different species were identified: Enterobacter hormaechei (n = 35, 62.5%), Escherichia coli (n = 12, 21.4%), Klebsiella pneumoniae (n = 5, 8.9%), Klebsiella oxytoca (n = 1, 1.8%), Klebsiella michiganensis (n = 1, 1.8%), Citrobacter freundii (n = 1, 1.8%), and Serratia marcesens (n = 1, 1.8%). E. hormaechei ST78 was the most common genotype (n = 14, 25%). Two major pOXA-48 plasmid types were identified throughout the outbreak, 'types' 1 and 2, and 5 major E. hormaechei clonal groupings were identified: ST78, ST108, ST1126, ST135, and ST66. Within each of the ST108, ST1126, ST135 and ST66 groups, the pOXA-48 harbored within each isolate were the same. Within ST78, 9 isolates contained the pOXA48 'type 2' plasmid and 5 contained the 'type 1' plasmid. Environmental specimens were taken from different outbreak ward locations: handwash basins, sink and shower drains, and taps. Of 394 environmental specimens, OXA-48 CPE was isolated from 26 (6.6%).ConclusionsThis prolonged outbreak of OXA-48 CPE was confined to one ward, but it exemplifies the complexity and difficulty in the control of these organisms. With multiple species and genotypes involved, they may be better described as 'plasmid outbreaks.' WGS provided insights into this diversity and potential transmission among cases, though its usefulness would be enhanced by analysis as close as possible to real time so that interventions can be implemented as soon as data are available.

| S-EPMC9495434 | biostudies-literature

Dissemination of OXA-48- and NDM-1-Producing Enterobacterales Isolates in an Algerian Hospital.

Project description:Multidrug-resistant (MDR) Enterobacterales remain an increasing problem in Algeria, notably due to the emergence of carbapenemase producers. We investigated the molecular characteristics of carbapenem-resistant Enterobacterales isolates recovered from outpatients and inpatients in Eastern Algeria. Non-repetitive Enterobacterales with reduced susceptibility to carbapenems were consecutively collected from clinical specimens in Annaba University Hospital (Algeria) between April 2016 and December 2018. Isolates were characterized with regard to antibiotic resistance, resistome and virulome content, clonality, and plasmid support. Of the 168 isolates analyzed, 29 (17.3%) were carbapenemase producers and identified as K. pneumoniae (n = 23), E. coli (n = 5), and E. cloacae (n = 1). blaOXA-48 was the most prevalent carbapenemase-encoding gene (n = 26/29), followed by blaNDM-1 gene (n = 3/29). K. pneumoniae isolates harbored some virulence traits (entB, ugeF, ureA, mrkD, fimH), whereas E. coli had a commensal origin (E, A, and B1). Clonality analysis revealed clonal expansions of ST101 K. pneumoniae and ST758 E. coli. Plasmid analysis showed a large diversity of incompatibility groups, with a predominance of IncM (n = 26, 89.7%). A global dissemination of OXA-48-producing Enterobacterales in the Algerian hospital but also the detection of NDM-1-producing E. coli in community settings were observed. The importance of this diffusion must be absolutely investigated and controlled.

| S-EPMC9220339 | biostudies-literature

OXA-48 dissemination during an outbreak

Project description:The molecular epidemiology of plasmid-based dissemination of OXA-48 during a hospital outbreak

| PRJEB34285 | ENA

Carbapenem Resistance Conferred by OXA-48 in K2-ST86 Hypervirulent Klebsiella pneumoniae, France.

Project description:We recovered 2 carbapenem-resistant K2-ST86 hypermucoviscous Klebsiella pneumoniae isolates from patients in France. The isolates had genetic attributes of hypervirulent K. pneumoniae but differed in ability to cause mouse lethality. Convergence of hypervirulent K. pneumoniae toward resistance could cause a health crisis because such strains could be responsible for severe and untreatable infections.

| S-EPMC7323517 | biostudies-literature

Hospital outbreak of carbapenem-resistant Enterobacterales associated with a blaOXA-48 plasmid carried mostly by Escherichia coli ST399.

Project description:A hospital outbreak of carbapenem-resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous blaOXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399 accounted for 35 of all the 55 isolates. Comparative genomics analysis using publicly available E. coli ST399 genomes showed that the outbreak E. coli ST399 isolates formed a unique clade. We developed a mathematical model of pOXA-48-like plasmid transmission between host lineages and used it to estimate its conjugation rate, giving a lower bound of 0.23 conjugation events per lineage per year. Our analysis suggests that co-evolution between the pOXA-48-like plasmid and E. coli ST399 could have played a role in the outbreak. This is the first study to report carbapenem-resistant E. coli ST399 carrying blaOXA-48 as the main cause of a plasmid-borne outbreak within a hospital setting. Our findings suggest complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.

| S-EPMC9453065 | biostudies-literature

Sequence-based epidemiology of an OXA-48 plasmid during a hospital outbreak.

Project description:Objectives. A large OXA-48 outbreak in the Netherlands involved the spread of OXA-48producing Enterobacteriaceae among at least 118 patients, suggesting horizontal transfer of this resistance gene through one or more plasmids. Elucidating transmission dynamics of resistance plasmids is hampered by the low resolution of classic typing methods. This study aimed to investigate the molecular epidemiology of plasmids carrying OXA-48 carbapenemase using a next-generation sequencing approach.Methods. A total of 68 OXA-48-producing Enterobacteriaceae isolated from the hospital outbreak, as well as 22 non-outbreak related OXA-48-producing Enterobacteriaceae from the Netherlands, Libya and Turkey were selected. Plasmids were sequenced using the Illumina Miseq platform, and read sets were assembled and analysed.Results. In all plasmids blaOXA-48 was embedded in transposon Tn1999.2 and located on a ca. 62 kb IncL/M conjugative plasmid in 14 different species. There were a maximum of 2 SNPs (single nucleotide polymorphisms) between the core sequence alignment of all plasmids. Closely related sequence variants of this plasmid were detected in non-outbreak isolates from the Netherlands and other countries. Thirty-one of 89 OXA-48-producing isolates also harboured blaCTX-M-15, which was not located on the blaOXA-48-carrying plasmid. Sequencing of four plasmids harbouring blaCTX-M15 revealed extensive plasmid heterogeneity.Conclusions. A ca 62 kb plasmid was responsible for the OXA-48 outbreak in a Dutch hospital. Our findings provide strong evidence for both within-host inter-species and between host dissemination of plasmid-based OXA-48 during a nosocomial outbreak. These findings exemplify the complex epidemiology of carbapenemase producing Enterobacteriaceae (CPE).

| S-EPMC6879230 | biostudies-literature

OXA-48 Carbapenemase-Producing Enterobacterales in Spanish Hospitals: An Updated Comprehensive Review on a Rising Antimicrobial Resistance.

Project description:Carbapenemase-producing Enterobacterales (CPE) are significant contributors to the global public health threat of antimicrobial resistance. OXA-48-like enzymes and their variants are unique carbapenemases with low or null hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins. CPEs have been classified by the WHO as high-priority pathogens given their association with morbidity and mortality and the scarce number of effective antibiotic treatments. In Spain, the frequency of OXA-48 CPE outbreaks is higher than in other European countries, representing the major resistance mechanism of CPEs. Horizontal transfer of plasmids and poor effective antibiotic treatment are additional threats to the correct prevention and control of these hospital outbreaks. One of the most important risk factors is antibiotic pressure, specifically carbapenem overuse. We explored the use of these antibiotics in Spain and analyzed the frequency, characteristics and prevention of CPE outbreaks. Future antibiotic stewardship programs along with specific preventive measures in hospitalized patients must be reinforced and updated in Spain.

| S-EPMC7832331 | biostudies-literature

A single Proteus mirabilis lineage from human and animal sources: a hidden reservoir of OXA-23 or OXA-58 carbapenemases in Enterobacterales.

Project description:In Enterobacterales, the most common carbapenemases are Ambler's class A (KPC-like), class B (NDM-, VIM- or IMP-like) or class D (OXA-48-like) enzymes. This study describes the characterization of twenty-four OXA-23 or OXA-58 producing-Proteus mirabilis isolates recovered from human and veterinary samples from France and Belgium. Twenty-two P. mirabilis isolates producing either OXA-23 (n = 21) or OXA-58 (n = 1), collected between 2013 and 2018, as well as 2 reference strains isolated in 1996 and 2015 were fully sequenced. Phylogenetic analysis revealed that 22 of the 24 isolates, including the isolate from 1996, belonged to a single lineage that has disseminated in humans and animals over a long period of time. The blaOXA-23 gene was located on the chromosome and was part of a composite transposon, Tn6703, bracketed by two copies of IS15∆II. Sequencing using Pacbio long read technology of OXA-23-producing P. mirabilis VAC allowed the assembly of a 55.5-kb structure encompassing the blaOXA-23 gene in that isolate. By contrast to the blaOXA-23 genes, the blaOXA-58 gene of P. mirabilis CNR20130297 was identified on a 6-kb plasmid. The acquisition of the blaOXA-58 gene on this plasmid involved XerC-XerD recombinases. Our results suggest that a major clone of OXA-23-producing P. mirabilis is circulating in France and Belgium since 1996.

| S-EPMC7280188 | biostudies-literature

Molecular identification of the source of an uncommon tularaemia outbreak, Germany, autumn 2016.

Project description:BackgroundIn 2016, an uncommon outbreak of oropharyngeal tularaemia involving six human cases occurred in Germany, caused by drinking contaminated fresh must after a grape harvest.AimWe describe the details of laboratory investigations leading to identification of the outbreak strain, its characterisation by next generation sequencing (NGS) and the finding of the possible source of contamination.MethodsWe incubated wine samples in different media and on agar plates. NGS was performed on DNA isolated from young wine, sweet reserve and an outbreak case's lymph node. A draft genome of the outbreak strain was generated. Vertebrate-specific PCRs using primers targeting the mitochondrial cytochrome b gene and product analyses by blast search were used to identify the putative source of must contamination.ResultsNo bacterial isolate could be obtained. Analysis of the draft genome sequence obtained from the sweet reserve attributed this sequence to Francisella tularensis subsp. holarctica, belonging to the B.12/B.34 phylogenetic clade (erythromycin-resistant biovar II). In addition, the DNA sequence obtained from the case's isolate supported our hypothesis that infection was caused by drinking contaminated must. The vertebrate-specific cytochrome b sequence derived from the young wine and the sweet reserve could be assigned to Apodemus sylvaticus (wood mouse), suggesting that a wood mouse infected with F. tularensis may have contaminated the must.ConclusionThe discovered source of infection and the transmission scenario of F. tularensis in this outbreak have not been observed previously and suggest the need for additional hygienic precautionary measures when processing and consuming freshly pressed must.

| S-EPMC6505183 | biostudies-literature

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