Household acquisition and transmission of extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae after hospital discharge of ESBL-positive index patients

Objectives: This study aimed to determine rates and risk factors of extended-spectrum b-lactamaseproducing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient. Methods: Two-year prospective cohort study in five European cities. Patients colonized with ESBLproducing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case. At each follow up, participants provided a faecal sample and personal information. ESBL-PE whole-genome sequences were compared using pairwise single nucleotide polymorphism-based analysis. Results: We enrolled 71 index patients carrying ESBL-Ec (n ¼ 45), ESBL-Kp (n ¼ 20) or both (n ¼ 6), and 102 household contacts. The incidence of any ESBL-PE acquisition among household members initially free of ESBL-PE was 1.9/100 participant-weeks at risk. Nineteen clonally related household transmissions occurred (case to contact: 13; contact to case: 6), with an overall rate of 1.18 transmissions/100 participant-weeks at risk. Most of the acquisition and transmission events occurred within the first 2 months after discharge. The rate of ESBL-Kp household transmission (1.16/100 participant-weeks) was higher than of ESBL-Ec (0.93/100 participant-weeks), whereas more acquisitions were noted for ESBL-Ec (1.06/100 participant-weeks) compared with ESBL-Kp (0.65/100 participant-weeks). Providing assistance for urinary and faecal excretion to the index case by household members increased the risk of ESBL-PE transmission (adjusted prevalence ratio 4.3; 95% CI 1.3e14.1).Instituto de Salud Carlos II

Household acquisition and transmission of extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae after hospital discharge of ESBL-positive index patients

MODERN WP2 study group: Caroline Brossier, Elodie von Dach, Gesuele Renzi, Jacques Schrenzel, Stefanie Bunk, Siri Goepel, Florian Hölzl, Michael Eib, Ingo B.Autenrieth, Álvaro Pascual, Xavier Bertrand, Jelle Scharringa, Patrick Musicha.[Objectives] This study aimed to determine rates and risk factors of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient.[Methods] Two-year prospective cohort study in five European cities. Patients colonized with ESBL-producing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case. At each follow up, participants provided a faecal sample and personal information. ESBL-PE whole-genome sequences were compared using pairwise single nucleotide polymorphism-based analysis.[Results] We enrolled 71 index patients carrying ESBL-Ec (n = 45), ESBL-Kp (n = 20) or both (n = 6), and 102 household contacts. The incidence of any ESBL-PE acquisition among household members initially free of ESBL-PE was 1.9/100 participant-weeks at risk. Nineteen clonally related household transmissions occurred (case to contact: 13; contact to case: 6), with an overall rate of 1.18 transmissions/100 participant-weeks at risk. Most of the acquisition and transmission events occurred within the first 2 months after discharge. The rate of ESBL-Kp household transmission (1.16/100 participant-weeks) was higher than of ESBL-Ec (0.93/100 participant-weeks), whereas more acquisitions were noted for ESBL-Ec (1.06/100 participant-weeks) compared with ESBL-Kp (0.65/100 participant-weeks). Providing assistance for urinary and faecal excretion to the index case by household members increased the risk of ESBL-PE transmission (adjusted prevalence ratio 4.3; 95% CI 1.3–14.1).[Conclusions] ESBL-PE cases discharged from the hospital are an important source of ESBL-PE transmission within households. Most acquisition and transmission events occurred during the first 2 months after hospital discharge and were causally related to care activities at home, highlighting the importance of hygiene measures in community settings.[Clinical study registration] German Clinical Trials Register, DRKS-ID: DRKS00013250.This study was part of a Joint Programming Initiative on Antimicrobial Resistance collaborative research project, under the 2016 Joint Call framework (Transnational Research Projects on the Transmission Dynamics of Antibacterial Resistance). It received funding from the following national research agencies: Instituto de Salud Carlos III (grant no. AC16/00076), Netherlands Organization for Health Research and Development (grant no. AC681055), Swiss National Science Foundation (grant no. 40AR40-173608), German Federal Ministry of Education and Research (grant no. 01KI1830) and Agence Nationale de la Recherche (grant no. ANR-16-JPEC-0007-03). As part of a separate research project, Marlieke de Kraker has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nos 115523, 115620 and 115737 (Combatting Bacterial Resistance in Europe projects (COMBACTE)), resources of which are composed of financial contribution from the European Union's 7th Framework Programme (FP7/2007±2013) and the European Federation of Pharmaceutical Industries and associations companies' in-kind contribution. Also, Elena Salamanca, Mercedes Delgado and Jesús Rodríguez-Baño received support for research from by the Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative Programme Intelligence Growth 2014-2020.Peer reviewe

Epidémiologie des bacilles à Gram négatif dans la communauté, l’environnement et la nourriture

Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa are Gram-negative bacilli frequently involved in nosocomial infections. Their dissemination in health care systems has been well characterized but the intestinal carriage and transmission dynamics of these pathogens in the community are poorly understood. The One Health concept supports the idea that bacterial populations found in humans, animals and the environment are interconnected. Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE), responsible for infections associated with high morbidity and mortality, are of particular interest because they widely contaminate food, which could thus be a source of EBLSE acquisition for consumers. We used a whole genome sequencing (WGS) approach on a large collection of isolates from residents of long-term care facilities, food and wastewater from five European cities. A first study showed that, in general, ESBL-PE populations from food and sewage are different and have different antibiotic resistance genes. This suggests that food is not a major source of ESBL-PE for humans. A second study found that residents of long-term care facilities were very frequent (51.6%) digestive carriers of P. aeruginosa. This carriage was associated with age and obesity and concerned a genetically very diverse population of P. aeruginosa. Overall, our data show that a complete understanding of the diffusion of Gram-negative bacilli and antibiotic resistance genes requires the examination of complete bacterial genomes.Escherichia coli, Klebsiella pneumoniae et Pseudomonas aeruginosa sont des bacilles à Gram négatif fréquemment responsables d’infections nosocomiales. Leur diffusion dans les systèmes de soins a été bien caractérisée mais le portage intestinal et les dynamiques de transmission de ces pathogènes dans la communauté sont mal connus. Le concept One Health supporte l’idée que les populations bactériennes trouvées chez les humains, les animaux et dans l’environnement sont interconnectées. Les entérobactéries productrices de β-lactamases à spectre étendu (EBLSE), responsables d’infections associées à une forte morbi-mortalité, présentent un intérêt particulier car elles contaminent largement la nourriture, qui pourrait être ainsi une source d’EBLSE pour les consommateurs. Nous avons utilisé une approche de whole genome sequencing (WGS) sur une large collection d’isolats provenant de résidents d’établissements de long séjour, d’aliments et d’eaux usées de cinq villes européennes. Une première étude a montré qu’en général les populations d’EBLSE issues d’aliments et d’eaux usées sont dissociées et possèdent des gènes de résistance aux antibiotiques différents. Ceci suggère que l’alimentation n’est pas une source majeure d’EBLSE pour l’homme. Une seconde étude a relevé que les résidents de centres de long séjour étaient très fréquemment (51,6%) porteurs digestifs de P. aeruginosa. Ce portage était associé à l’âge et à l’obésité et concernait une population de P. aeruginosa génétiquement très diverse. Globalement, nos données montrent que la compréhension complète de la diffusion des bacilles à Gram négatif et celle des gènes de résistance aux antibiotiques requiert l’examen des génomes bactériens complets

Epidémiologie des bacilles à Gram négatif dans la communauté, l’environnement et la nourriture

Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa are Gram-negative bacilli frequently involved in nosocomial infections. Their dissemination in health care systems has been well characterized but the intestinal carriage and transmission dynamics of these pathogens in the community are poorly understood. The One Health concept supports the idea that bacterial populations found in humans, animals and the environment are interconnected. Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE), responsible for infections associated with high morbidity and mortality, are of particular interest because they widely contaminate food, which could thus be a source of EBLSE acquisition for consumers. We used a whole genome sequencing (WGS) approach on a large collection of isolates from residents of long-term care facilities, food and wastewater from five European cities. A first study showed that, in general, ESBL-PE populations from food and sewage are different and have different antibiotic resistance genes. This suggests that food is not a major source of ESBL-PE for humans. A second study found that residents of long-term care facilities were very frequent (51.6%) digestive carriers of P. aeruginosa. This carriage was associated with age and obesity and concerned a genetically very diverse population of P. aeruginosa. Overall, our data show that a complete understanding of the diffusion of Gram-negative bacilli and antibiotic resistance genes requires the examination of complete bacterial genomes.Escherichia coli, Klebsiella pneumoniae et Pseudomonas aeruginosa sont des bacilles à Gram négatif fréquemment responsables d’infections nosocomiales. Leur diffusion dans les systèmes de soins a été bien caractérisée mais le portage intestinal et les dynamiques de transmission de ces pathogènes dans la communauté sont mal connus. Le concept One Health supporte l’idée que les populations bactériennes trouvées chez les humains, les animaux et dans l’environnement sont interconnectées. Les entérobactéries productrices de β-lactamases à spectre étendu (EBLSE), responsables d’infections associées à une forte morbi-mortalité, présentent un intérêt particulier car elles contaminent largement la nourriture, qui pourrait être ainsi une source d’EBLSE pour les consommateurs. Nous avons utilisé une approche de whole genome sequencing (WGS) sur une large collection d’isolats provenant de résidents d’établissements de long séjour, d’aliments et d’eaux usées de cinq villes européennes. Une première étude a montré qu’en général les populations d’EBLSE issues d’aliments et d’eaux usées sont dissociées et possèdent des gènes de résistance aux antibiotiques différents. Ceci suggère que l’alimentation n’est pas une source majeure d’EBLSE pour l’homme. Une seconde étude a relevé que les résidents de centres de long séjour étaient très fréquemment (51,6%) porteurs digestifs de P. aeruginosa. Ce portage était associé à l’âge et à l’obésité et concernait une population de P. aeruginosa génétiquement très diverse. Globalement, nos données montrent que la compréhension complète de la diffusion des bacilles à Gram négatif et celle des gènes de résistance aux antibiotiques requiert l’examen des génomes bactériens complets

Epidemiology of Gram-negative bacilli in the community, the environment and food products

Escherichia coli, Klebsiella pneumoniae et Pseudomonas aeruginosa sont des bacilles à Gram négatif fréquemment responsables d’infections nosocomiales. Leur diffusion dans les systèmes de soins a été bien caractérisée mais le portage intestinal et les dynamiques de transmission de ces pathogènes dans la communauté sont mal connus. Le concept One Health supporte l’idée que les populations bactériennes trouvées chez les humains, les animaux et dans l’environnement sont interconnectées. Les entérobactéries productrices de β-lactamases à spectre étendu (EBLSE), responsables d’infections associées à une forte morbi-mortalité, présentent un intérêt particulier car elles contaminent largement la nourriture, qui pourrait être ainsi une source d’EBLSE pour les consommateurs. Nous avons utilisé une approche de whole genome sequencing (WGS) sur une large collection d’isolats provenant de résidents d’établissements de long séjour, d’aliments et d’eaux usées de cinq villes européennes. Une première étude a montré qu’en général les populations d’EBLSE issues d’aliments et d’eaux usées sont dissociées et possèdent des gènes de résistance aux antibiotiques différents. Ceci suggère que l’alimentation n’est pas une source majeure d’EBLSE pour l’homme. Une seconde étude a relevé que les résidents de centres de long séjour étaient très fréquemment (51,6%) porteurs digestifs de P. aeruginosa. Ce portage était associé à l’âge et à l’obésité et concernait une population de P. aeruginosa génétiquement très diverse. Globalement, nos données montrent que la compréhension complète de la diffusion des bacilles à Gram négatif et celle des gènes de résistance aux antibiotiques requiert l’examen des génomes bactériens complets.Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa are Gram-negative bacilli frequently involved in nosocomial infections. Their dissemination in health care systems has been well characterized but the intestinal carriage and transmission dynamics of these pathogens in the community are poorly understood. The One Health concept supports the idea that bacterial populations found in humans, animals and the environment are interconnected. Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE), responsible for infections associated with high morbidity and mortality, are of particular interest because they widely contaminate food, which could thus be a source of EBLSE acquisition for consumers. We used a whole genome sequencing (WGS) approach on a large collection of isolates from residents of long-term care facilities, food and wastewater from five European cities. A first study showed that, in general, ESBL-PE populations from food and sewage are different and have different antibiotic resistance genes. This suggests that food is not a major source of ESBL-PE for humans. A second study found that residents of long-term care facilities were very frequent (51.6%) digestive carriers of P. aeruginosa. This carriage was associated with age and obesity and concerned a genetically very diverse population of P. aeruginosa. Overall, our data show that a complete understanding of the diffusion of Gram-negative bacilli and antibiotic resistance genes requires the examination of complete bacterial genomes

Origin, fluxes, and reservoirs of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in aquatic ecosystems of a French floodplain

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Genomic characterization of a local epidemic Pseudomonas aeruginosa reveals specific features of the widespread clone ST395

International audiencePseudomonas aeruginosa is a ubiquitous opportunistic pathogen with several clones being frequently associated with outbreaks in hospital settings. ST395 is among these so-called 'international' clones. We aimed here to define the biological features that could have helped the implantation and spread of the clone ST395 in hospital settings. The complete genome of a multidrug resistant index isolate (DHS01) of a large hospital outbreak was analysed. We identified DHS01-specific genetic elements, among which were identified those shared with a panel of six independent ST395 isolates responsible for outbreaks in other hospitals. DHS01 has the fifth largest chromosome of the species (7.1 Mbp), with most of its 1555 accessory genes borne by either genomic islands (GIs, n=48) or integrative and conjugative elements (ICEs, n=5). DHS01 is multidrug resistant mostly due to chromosomal mutations. It displayed signatures of adaptation to chronic infection in part due to the loss of a 131 kbp chromosomal fragment. Four GIs were specific to the clone ST395 and contained genes involved in metabolism (GI-4), in virulence (GI-6) and in resistance to copper (GI-7). GI-7 harboured an array of six copper transporters and was shared with non-pathogenic Pseudomonas sp. retrieved from copper-contaminated environments. Copper resistance was confirmed phenotypically in all other ST395 isolates and possibly accounted for the spreading capability of the clone in hospital outbreaks, where water networks have been incriminated. This suggests that genes transferred from copper-polluted environments may have favoured the implantation and spread of the international clone P. aeruginosa ST395 in hospital settings

Fourier-Transform InfraRed Spectroscopy Can Quickly Type Gram-Negative Bacilli Responsible for Hospital Outbreaks

International audienceThe typing of epidemic bacterial pathogens in hospitals relies on DNA-based, expensive, and time-consuming techniques, that are often limited to retrospective studies. However, the quick identification of epidemic pathogens in the routine of the microbiology laboratories would expedite infection control procedures that limit the contamination of new patients. IR Biotyper (Bruker Daltonics GmbH) is a new typing machine based on Fourier-transform infrared (FTIR) spectroscopy which generates spectra, aiming at typing the micro-organisms within 3 h. This technique discriminates the isolates by exploring the differences of the surface cell polysaccharides. In this work, we evaluated the ability of the FTIR spectroscopy to recognize Gram-negative bacilli clones responsible for hospital outbreaks. Isolates of Pseudomonas aeruginosa (n = 100), Klebsiella pneumoniae (n = 16), Enterobacter cloacae (n = 23), and Acinetobacter baumannii (n = 20) were typed by the reference methods Multi-Locus Sequence Typing (defining sequence types - STs) along with or without pulsed field gel electrophoresis (PFGE) (defining pulsotypes), and by FTIR spectroscopy. The congruence of FTIR spectroscopy clustering was compared to those of MLST and PFGE by Adjusted Rand index and Adjusted Wallace coefficient. We found that FTIR spectroscopy accurately clustered P. aeruginosa, K. pneumoniae, and E. cloacae isolates belonging to the same ST. The performance of the FTIR spectroscopy was slightly lower for A. baumannii. Furthermore, FTIR spectroscopy also correctly clustered P. aeruginosa isolates having a similar pulsotype. Overall, the IR Biotyper can quickly (in less than 3 h) detect the spread of clones of P. aeruginosa, K. pneumoniae, E. cloacae, and A. baumannii. The use of this technique by clinical microbiology laboratories may help to tackle the spread of epidemic clones by the quick implementation of infection control measures

Populations of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae are different in human-polluted environment and food items: a multicentre European study

Objectives To assess the extent to which food items are a source of extended-spectrum β-lactamase (ESBL) -producing Escherichia coli (ESBL-Ec) and ESBL-producing Klebsiella pneumoniae (ESBL-Kp) for humans in five European cities. Methods We sampled 122 human polluted (hp)-environments (sewers and polluted rivers, as a proxy of human contamination) and 714 food items in Besançon (France), Geneva (Switzerland), Sevilla (Spain), Tübingen (Germany) and Utrecht (The Netherlands). A total of 254 ESBL-Ec and 39 ESBL-Kp isolates were cultured. All genomes were fully sequenced to compare their sequence types (ST) and core genomes, along with the distribution of blaESBL genes and their genetic supports (i.e. chromosome or plasmid). Results Sequence data revealed that ESBL-Ec and ESBL-Kp isolates from hp-environments were genetically different from those contaminating food items. ESBL-Ec ST131 was widespread in the hp-environment (21.5% of the isolates) but absent from the food items tested. ESBL-Ec ST10 was in similar proportions in hp-environments and food items (15 and 10 isolates, respectively) but mostly carried reservoir-specific blaESBL. blaCTX-M-1 and blaSHV-12 predominated in food-related E. coli isolates (32% and 34% of the isolates, respectively), whereas blaCTX-M-15 and blaCTX-M-27 predominated in isolates from hp-environments (52% and 15% of the isolates, respectively). Conclusions We found a very limited connection between ESBL-Ec and ESBL-Kp populations retrieved in food items and from hp-environments and blaESBL. This suggests that human-to-human contamination, rather than the food chain, is possibly the most frequent route of ESBL-Ec and ESBL-Kp transmission in high-income countries

The Fate of Antibiotic-Resistant Bacteria in the Environment

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