Bakgrund: Multiresistenta bakterier är ett globalt växande samhällsproblem och ett utav de största folkhälsoproblemen. Förekomsten av multiresistenta bakterier ökar genom användning av antibiotika, framförallt bred-spektrumantibiotika. Multiresistenta bakterier leder till ökad sjuklighet och dödlighet, längre vårdtider och spridning sker både i samhället samt på sjukhus. MRSA, ESBL, VRE och MDR-TB är de multiresistenta bakterier som litteraturstudien fokuserar på. Syfte: Syftet var att belysa sjuksköterskans erfarenheter av att vårda patienter med multiresistenta bakterier. Metod: En allmän litteraturstudie med kvalitativ metod och induktiv ansats utfördes. Åtta vetenskapliga artiklar granskades och analyserades tills kategorier identifierades. Resultat: Analysen resulterade i att fem kategorier identifierades: sjuksköterskans rädslor, otillräcklig kunskap, sjuksköterskans ansvar, organisatoriska brister och utmaningar med patienter i isolering. Sjuksköterskorna beskrev att det förekom hinder i vårdandet av patienter med multiresistenta bakterier såsom bristande kunskap och ledarskap, rädsla för att smittas och smitta andra, avsaknad av riktlinjer samt isolering av patienter. Konklusion: Sjuksköterskor behöver mer kunskap och goda förutsättningar för att kunna ge patienter med multiresistenta bakterier optimal vård. / Background: Multidrug-resistant bacteria are a globally growing problem in society and one of the largest public health problems. The occurrence of multidrug-resistant bacteria increases through the use of antibiotics, especially broad-spectrum antibiotics. Multidrug-resistant bacteria leads to increased morbidity and mortality as well as longer treatments, and the bacteria are spread in both society and in hospitals. The literature study focuses on the multidrug-resistant bacteria MRSA, ESBL, VRE and MDR-TB. Aim: The aim was to illustrate the nurse''s experiences of caring for patients with multidrug-resistant bacteria. Method: A general literature study with a qualitative method and an inductive approach was carried out. Eight scientific articles were reviewed and analyzed until categories were identified. Results: The analysis resulted in five categories being identified: the nurse''s fears, insufficient knowledge, the nurse''s responsibilities, organizational deficiencies and challenges with patients in isolation. The nurses'' described obstacles in the care of patients with multiresistant bacteria such as lack of knowledge and leadership, fear of being infected and infecting others, lack of guidelines and isolation of patients. Conclusion: Nurses need more knowledge and good conditions to be able to give patients with multidrug-resistant bacteria optimal care.

Avian pathogenic Escherichia. coli (APEC) and Campylobacter are pathogenic threats to poultry and human health, respectively. In this study, the prevalence of these pathogens in Mississippi broilers and their antimicrobial resistance (AMR) properties were investigated, and a multidrug-resistant APEC strain (APEC-O2-MS1170) was further explored by whole-genome sequencing (WGS). The efficacy of in ovo injection of Lactobacillus in reducing the APEC in broilers was evaluated. Results revealed a high prevalence of APEC and Campylobacter in broilers and broiler products. A lot of isolates were resistant to antibiotics of different sorts. Moreover, the in ovo administration of Lactobacillus did not reduce the incidence of APEC. The WGS of APEC-O2-MS1170 revealed its detailed AMR and virulence properties and alerted a potential zoonotic risk. In conclusion, the Lactobacillus did not reduce the incidence of APEC in broilers, and the prevalence and AMR of APEC and Campylobacter are still challenges faced by the poultry industry.

The intestinal tract of virtually any metazoan, including mammals, is colonized with a complex microbial community to which we refer as intestinal or gut microbiota. One of the roles of the healthy intestinal microbiota is to protect the host against gut colonization with pathogenic bacteria through a phenomenon known as colonization resistance (CR). Dysbiosis of the intestinal microbiota, usually as a result of an antibiotic treatment, may lead to the disruption of the CR, and subsequent colonization with bacterial pathogens. However, and despite the importance, the role of the microbiota dysbiosis on the gut colonization by many bacterial pathogens, such as multidrug resistant Enterobacteriaceae, has not been elucidated: the members of the microbiota that confer CR and factors that promote colonization remain mostly unknown. The general aim of this thesis has been to improve the understanding of the role of the microbiota dysbiosis in gut colonization by bacterial pathogens. For this purpose, 3 projects have been established. In the first project we tried to elucidate the role of the microbiota dysbiosis on colonization by multidrug resistant Enterobacteriaceae (MRE) in mice. In the second project we investigated the risk factors and members of the microbiota associated with the MRE colonization in hospitalized patients. MRE infections represent a great threat for hospitalized patients. Specifically, acute leukemia patients are often colonized with MRE, probably due to the impaired CR as a result of intensive antibiotic treatments these patients receive. In the third project we studied the role of the microbiota dysbiosis on the development of Epizootic Rabbit Enteropathy (ERE). ERE is a severe gastrointestinal disease with a high percentage of mortality that occurs in young rabbits during first weeks post-weaning. ERE rabbits have been shown to suffer microbiota dysbiosis during the development of the disease. Moreover, the disease could be reproduced by contact between healthy and sick animals and by administration of cecal contents from ERE rabbits to healthy rabbits, suggesting that a pathogenic agent may be involved in the development of this intestinal pathology, although no causative agent has been identified until now. / El tracto intestinal de prácticamente cualquier metazoo, incluidos los mamíferos, está colonizado por una compleja comunidad microbiana a la que nos referimos como microbiota intestinal. Uno de los papeles de la microbiota intestinal es proteger al huésped contra la colonización intestinal con bacterias patógenas a través de un fenómeno conocido como resistencia a la colonización (RC). La disbiosis de la microbiota intestinal, a menudo como resultado de un tratamiento antibiótico, puede conducir a la alteración de la RC y posterior colonización por patógenos bacterianos. Sin embargo, y pese a su importancia, el papel de la disbiosis de la microbiota en la colonización intestinal por muchos patógenos bacterianos, como son las Enterobacterias multirresistentes, no se ha esclarecido: los miembros de la microbiota que confieren RC y los factores que promueven la colonización siguen siendo desconocidos. El objetivo general de esta tesis ha sido mejorar la comprensión del papel de disbiosis de la microbiota en la colonización intestinal por patógenos bacterianos. Para ello se han establecido tres proyectos. En el primer proyecto investigamos el papel de disbiosis de la microbiota intestinal en la colonización por Enterobacterias multiresistentes (MRE) en ratones. En el segundo proyecto investigamos los factores de riesgo y los miembros de la microbiota asociados con la colonización por MRE en pacientes hospitalizados. Las infecciones por MRE representan una gran amenaza para los pacientes hospitalizados. Específicamente, MRE a menudo colonizan los pacientes con leucemia aguda, probablemente debido a que la RC está alterada como resultado de tratamientos antibióticos intensivos recibidos por estos pacientes. En el tercer proyecto investigamos el papel de la disbiosis microbiana en desarollo de Enteropatía Epizoótica de Conejo (ERE). ERE es una enfermedad gastrointestinal severa con un alto porcentaje de mortalidad que ocurre en conejos jóvenes durante las primeras semanas después del destete. Se ha demostrado que los conejos con ERE sufren disbiosis microbiana después del inicio de la enfermedad, aunque no está claro el papel de la disbiosis en el desarollo de la enfermedad. Además, la enfermedad puede ser reproducida por contacto entre animales sanos y enfermos y por la administración del contenido cecal de conejos con ERE a conejos sanos, lo que sugiere que un agente patógeno podría estar implicado en el desarrollo de esta patología intestinal, aunque hasta ahora no se ha logrado identificar ningún agente causal. / El tracte intestinal de pràcticament qualsevol metazoo, inclosos els mamífers, està colonitzat per una complexa comunitat microbiana a la qual ens referim com microbiota intestinal. Un dels papers de la microbiota intestinal és protegir a l'hoste contra la colonització intestinal amb bacteris patògens a través d'un fenomen conegut com a resistència a la colonització (RC). La disbiosis de la microbiota intestinal, frecuentment com a resultat d'un tractament antibiòtic, pot conduir a l'alteració de la RC i posterior colonització per patògens bacterians. No obstant això, i malgrat la seva importància, el paper de la disbiosis de la microbiota en la colonització intestinal per molts patògens bacterians, com són les Enterobacteries multirresistentes, no s'ha esclarit: els membres de la microbiota que confereixen RC i els factors que promouen la colonització segueixen sent desconeguts. L'objectiu general d'aquesta tesi ha estat millorar la comprensió del paper de la disbiosis de la microbiota en la colonització intestinal per patògens bacterians. Per a això s'han establert tres projectes. En el primer projecte vam investigar el paper de la disbiosis de la microbiota intestinal en la colonització per Enterobacteries multiresistentes (MRE) en ratolins. En el segon projecte, investiguem els factors de risc i els membres de la microbiota associats amb la colonització per MRE en pacients hospitalitzats. Les infeccions per MRE representen una gran amenaça per als pacients hospitalitzats. Específicament, MRE sovint colonitza els pacients amb leucèmia aguda, probablement a causa de que la RC està alterada com a resultat de tractaments antibiòtics intensius rebuts per aquests pacients. En el tercer projecte, vam investigar el paper de la disbiosis microbiana en desenvolupament de l'Enteropatía Epizoótica de Conill (ERE). ERE és una malaltia gastrointestinal severa amb un alt percentatge de mortalitat que ocorre en conills joves durant les primeres setmanes després del deslleti. S'ha demostrat que els conills amb ERE sofreixen disbiosis microbiana després de l'inici de la malaltia, encara que no és clar el paper de la disbiosis en el desenvolupament de la malaltia. A més, la malaltia pot ser reproduïda per contacte entre animals sans i malalts i per l'administració del contingut cecal de conills amb ERE a conills sans, la qual cosa suggereix que un agent patogen podria estar implicat en el desenvolupament d'aquesta patologia intestinal, encara que fins ara no s'ha aconseguit identificar cap agent causal. / Djukovic, A. (2017). Role of intestinal dysbiosis on gut colonization by bacterial pathogens [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/90415

Yes / We investigated whether companion drug resistance was associated with adverse outcome of the shorter MDR-TB regimen in Bangladesh, after adjusting for fluoroquinolone resistance. MDR/RR-TB patients registered for treatment with a standardized gatifloxacin-based shorter MDR-TB regimen were selected for the study. Drug resistance was determined using the proportion method, gatifloxacin and isoniazid minimum inhibitory concentration testing for selected isolates, and whole genome sequencing. Low-level and high-level fluoroquinolone resistance were the most important predictors of adverse outcomes, with pyrazinamide resistance having a significant yet lower impact. In patients with fluoroquinolone-/second-line injectable-susceptible TB, non-eligibility to the shorter MDR-TB regimen (initial resistance to either pyrazinamide, ethionamide, or ethambutol) was not associated with adverse outcome (aOR 1.01; 95%CI 0.4-2.8). Kanamycin resistance was uncommon (1.3%). Increasing levels of resistance to isoniazid predicted treatment failure, also in a subgroup of patients with high-level fluoroquinolone-resistant TB. Our results suggest that resistance to companion drugs of the shorter MDR-TB regimen, except kanamycin resistance, is of no clinical importance as long as fluoroquinolone susceptibility is preserved. Hence, contrary to current WHO guidelines, exclusions to the standard regimen are justified only in the case of fluoroquinolone, and possibly kanamycin resistance. / Damien Foundation Belgium for its financial and logistic support to run the project including its research activities. European Research Council (Starting Grant INTERRUPTB 311725).

Yes / Mutations in the gyrase genes cause fluoroquinolone resistance in Mycobacterium tuberculosis. However, the predictive value of these markers for clinical outcomes in patients with MDR-TB is unknown to date. The objective of this study was to determine molecular markers and breakpoints predicting second-line treatment outcomes in M. tuberculosis patients treated with fourth-generation fluoroquinolones. We analysed treatment outcome data in relation to the gyrA and gyrB sequences and MICs of ofloxacin, gatifloxacin and moxifloxacin for pretreatment M. tuberculosis isolates from 181 MDR-TB patients in Bangladesh whose isolates were susceptible to injectable drugs. The gyrA 90Val, 94Gly and 94Ala mutations were most frequent, with the highest resistance levels for 94Gly mutants. Increased pretreatment resistance levels (>2 mg/L), related to specific mutations, were associated with lower cure percentages, with no cure in patients whose isolates were resistant to gatifloxacin at 4 mg/L. Any gyrA 94 mutation, except 94Ala, predicted a significantly lower proportion of cure compared with all other gyrA mutations taken together (all non-94 mutants + 94Ala) [OR = 4.3 (95% CI 1.4-13.0)]. The difference in treatment outcome was not explained by resistance to the other drugs. Our study suggests that gyrA mutations at position 94, other than Ala, predict high-level resistance to gatifloxacin and moxifloxacin, as well as poor treatment outcome, in MDR-TB patients in whom an injectable agent is still effective.

Tuberculosis (TB) is the world’s most deadly infectious disease and causes enormous public health problems. The comorbidity with HIV and the rise of multidrug-resistant TB strains impede successful therapy through drug-drug interactions and the lack of efficient second-line treatments. The aim of this thesis was to support the improvement of anti-TB therapy through development of pharmacometric models, specifically focusing on the novel drug bedaquiline, pharmacokinetic interactions and methods for pooled population analyses. A population pharmacokinetic model of bedaquiline and its metabolite M2, linked to semi-mechanistic models of body weight and albumin concentrations, was developed and used for exposure-response analysis. Treatment response was quantified by measurements of mycobacterial load and early bedaquiline exposure was found to significantly impact the half-life of bacterial clearance. The analysis represents the first successful characterization of a concentration-effect relationship for bedaquiline. Single-dose Phase I studies investigating potential interactions between bedaquiline and efavirenz, nevirapine, ritonavir-boosted lopinavir, rifampicin and rifapentine were analyzed with a model-based approach. Substantial effects were detected in several cases and dose-adjustments mitigating the impact were suggested after simulations. The interaction effects of nevirapine and ritonavir-boosted lopinavir were also confirmed in patients with multidrug-resistant TB on long-term treatment combining the antiretrovirals and bedaquiline. Furthermore, the outcomes from model-based analysis were compared to results from conventional non-compartmental analysis in a simulation study. Non-compartmental analysis was found to consistently underpredict the interaction effect when most of the concentration-time profile was not observed, as commonly is the case for compounds with very long terminal half-life such as bedaquiline. To facilitate pooled analyses of individual patient data from multiple sources a structured development procedure was outlined and a fast diagnostic tool for extensions of the stochastic model components was developed. Pooled analyses of nevirapine and rifabutin pharmacokinetics were performed; the latter generating comprehensive dosing recommendations for combined administration of rifabutin and antiretroviral protease inhibitors. The work presented in this thesis demonstrates the usefulness of pharmacometric techniques to improve treatment of TB and especially contributes evidence to inform optimized dosing regimens of new and old anti-TB drugs in various clinical contexts.

The aim of this thesis was to isolate the compounds responsible for the antibacterial activity of cell extracts of the marine diatom, Phaeodactylum tricornutum. Marine microalgae are not only important primary producers but, due to their phylogenetic diversity, they are also a potential source of novel bioactive compounds. The marine diatom, P. tricornutum, was selected for study because its cell extracts are known to be antibacterial but the compounds responsible have not been isolated. In this thesis, the compounds responsible for the antibacterial activity are isolated from aqueous methanol P. tricornutum cell extracts by column chromatography and reverse phase high-performance liquid chromatography using a bioassay-guided approach. The compounds in three active fractions were identified by mass spectrometry and nuclear magnetic resonance spectroscopy as the unsaturated fatty acids (5Z, 8Z, 11Z, 14Z, 17Z)-eicosapentaenoic acid, (9Z)-hexadecenoic acid and (6Z, 9Z, 12Z)-hexadecatrienoic acid. The fatty acids were found to be antibacterial against Staphylococcus aureus at micromolar concentrations. P. tricornutum exists in different cell morphs and, interestingly, extracts prepared from cultures in the fusiform morph were found to have greater antibacterial activity than extracts from oval cultures. This is explained by greater levels of the three antibacterial fatty acids in the fusiform cell extracts. The antibacterial fatty acids are proposed to be released by enzyme action when the diatom cells lose their integrity. The release of free fatty acids by diatoms is suggested to be a simple, very low cost population-level activated defence mechanism against potential pathogenic bacteria triggered when the cell loses its integrity. Further, this pathway may act against multiple threats to the microalga, including grazers, as fatty acids exhibit activity in diverse biological assays. Finally, whilst two of the fatty acids, (9Z)-hexadecenoic acid and (5Z, 8Z, 11Z, 14Z, 17Z)-eicosapentaenoic acid, inhibited the growth of MRSA their usefulness as therapeutic compounds may be limited due to their instability and their broad biological activity.

A tuberculose multirresistente (TBMR) - resistência simultânea a rifampicina e isoniazida, principais fármacos do esquema de tratamento da tuberculose (TB), gera mais ônus aos doentes e aos Serviços de Saúde, pois acarreta maiores custos, aumenta o tempo de tratamento e relaciona-se a prognósticos desfavoráveis. A TBMR ocorre devido à falha em algum princípio do tratamento, seja por parte dos profissionais e serviços de saúde, seja por questões ligadas ao doente. Frente a isso, o presente estudo objetivou identificar e analisar as condições de produção da TBMR relacionadas ao doente e seu entorno. Esta investigação foi realizada junto aos sujeitos em seguimento em um hospital de referência do interior paulista, entre janeiro de 2010 a janeiro de 2012. Foi utilizada a abordagem qualitativa. Por meio da análise dos prontuários médicos do serviço terciário, caracterizamos o universo do estudo - composto por todos os doentes já seguidos pela instituição, descrevendo e analisando dados sociodemográficos e clínicos correspondentes. Caracterizamos, também, a amostra estudada, formada por oito doentes de TBMR em seguimento, detalhando seu contexto de vida e trajetória com a doença, assim como a estruturação municipal para seu acompanhamento. A segunda etapa do trabalho constituiu na análise das percepções dos sujeitos a cerca do adoecimento por TB e pela forma MR. Os dados foram coletados por meio de entrevistas semi-estruturadas, gravadas e transcritas na íntegra. Os textos resultantes constituíram o corpus do estudo, organizado com recurso do software Atlas. Ti versão 7.0 e analisado sob o referencial teórico da Análise de Discurso, de matriz francesa. Os resultados da investigação baseiam-se na análise de três aspectos: percurso diagnóstico - em que é apontadas a percepção da doença e dos sintomas, as histórias pessoais e familiares do adoecimento por TB, o desenvolver até a obtenção do diagnóstico e as histórias de fracasso dos tratamentos convencionais; tratamento e acompanhamento dos casos MR - momento em que são discutidas questões ligadas a percepção do tratamento pelos doentes, as modalidades de supervisão empreendidas, os instrumentos e insumos fornecidos, além do apoio da rede familiar; coordenação da assistência - em que são analisadas as nuances da relação entre os diferentes serviços envolvidos na atenção ao doente, tanto dentro do mesmo nível assistencial quanto em sua intersecção com a atenção terciária, a fim de compreender suas fragilidades e promover as potencialidades para o tratamento dos sujeitos. Essas condições de produção mostraram-se complexas, ao passo que sofrem influência das peculiaridades da forma como os serviços locais de atenção organizando-se para atender esses doentes, além de questões relacionadas à trajetória de vida e doença desses sujeitos, apontando para a necessidade de ampliação do espaço de negociação dentro do sistema de saúde. / Multidrug-resistant tuberculosis - simultaneous resistance to rifampicin and isoniazid, the main drugs in the treatment for tuberculosis (TB), generates more onuses to patients and Health Services because it involves higher costs, increases the treatment time and relates to the unfavorable outcomes. MDR-TB occurs due to failure in some treatment principles, either by professionals and health services, or by patient issues. Concerning this, the present study aimed to identify and analyze the conditions of MDR-TB production related to the patients and their surroundings. This investigation was conducted with the subjects followed up in a referral hospital in São Paulo State, between January 2010 and January 2012. It was used a qualitative approach. By analyzing the medical records of the tertiary service, we characterized the universe of the study - consisting of all patients who were already followed by the institution, describing and analyzing the demographic and clinical data matching. We also characterized the sample, formed by eight MDR-TB patients in follow-up, detailing the context of their lives and the disease trajectory, as well as the municipal structure to monitor them. The second stage of the work consisted of analyzing the subjects\' perceptions about TB development and MR strain. Data was collected through semi-structured interviews which were recorded and fully transcribed. The resulting texts constituted the corpus of the study, organized using the Atlas.Ti software version 7.0 and analyzed from the theoretical framework of Discourse Analysis of French matrix. The results are based on analysis of three aspects: The first is diagnosis route - which shows the disease and symptoms perception of the patient, personal and family histories of TB development, the disease development until the diagnosis, and the failed conventional treatment stories. The second aspect was treatment and monitoring of MDR cases - when cases are discussed we focused on the following aspects: perceptions of treatment by patients, undertaken methods of supervision, instruments and inputs provided, and the familiar support network. The third is assistance coordination - where the nuances of the relationship between several departments involved in the patient care are analyzed, within the same care level as well as its intersection with tertiary care in order to understand their weaknesses and promote the potential treatments for the subjects. These production conditions proved to be complex whereas the local care services peculiarities influence the way they are organized to assist these patients, as well as aspects related to life and illness trajectory of these subjects, indicating the need of expanding the negotiation space within the health system

Text in English / Aim: The aims of this study were to investigate the treatment outcomes of patients with MDRTB and its determinants at referral hospitals in Ethiopia. The study also aims to develop a conceptual model for enhancing treatment of patients with MDR-TB in Ethiopia. Design and methods: A concurrent mixed methods design with quantitative dominance was used to investigate treatment outcomes of patients with MDR-TB and its determinants. Results: A total of 136 (n=136) patients with MDR-TB participated in the study, 74 (54%) were male and 62 (46%) were female. Forty-one (31%) of the patients had some co-morbidity with MDR-TB at baseline, and 64% had body mass index less than 18.5kg/m2. Eight (6%) of the patients were diagnosed among household contacts. At 24 months, 76/110 (69%) of the patients had successfully completed treatment, but 30/110 (27%) were died of MDR-TB. Multivariable logistic regression revealed that the odds of unfavourable treatment outcomes were significantly higher among patients with low body mass index (BMI <18.5kg/m2) (AOR=2.734, 95% CI: 1.01-7.395; P<0.048); and those with some co-morbidity with MDR-TB at the baseline (AOR=4.260, 95%CI: 1.607-11.29; p<0.004). The majority of the patients were satisfied with the clinical care they received at hospitals. But as no doctor was exclusively dedicated for the MDR-TB centre, patients could not receive timely medical attention and this was especially the case with those with emergency medical conditions. The caring practice of caregivers at the hospitals was supportive and empathic but it was desperate and alienating at treatment follow up centres. Patients were dissatisfied with the quality and adequacy of the socio-economic support they got from the programme. Despite the high MDR-TB and HIV/AIDS co-infection rate, services for both diseases was not available under one roof. Conclusions: Low body mass index and the presence of any co-morbidity with MDR-TB at the baseline are independent predictors of death among patients with MDR-TB. Poor communication between patients and their caregivers and inadequate socio-economic support were found to determine patients’ perceived quality of care and patients’ satisfaction with care given for MDR-TB. / Health Studies / D. Litt et Phil. (Health Studies)

Animais de companhia têm sido apontados como reservatórios de bactérias gram-negativas resistentes a antibióticos utilizados em medicina humana e veterinária. O objetivo deste estudo foi investigar a prevalência da resistência mediada por plasmídeos em bactérias Gram-negativas isoladas de animais de companhia no Brasil e na França, elucidando o papel potencial desses animais como portadores assintomáticos. Amostras de DNA extraídas de quatro coleções de bactérias Gram-negativas produtoras de ESBL foram analisadas por tipagem e sub-tipagem baseados em PCR, análise do polimorfismo de comprimento de fragmentos de restrição (RFLP), dimensionamento baseado em PFGE de nuclease S1 e hibridação Southern blot. Adicionalmente, isolados de Escherichia coli, Klebsiella pneumoniae e Enterobacter cloacae foram caracterizados por PFGE (Pulsed-field Gel Electrophoresis) e Multilocus Sequence Typing, agrupamento filogenético e tipagem de O25b. A presença de plasmídeos IncH12 (~600-kb) e IncFIB (~210-290-kp) carregando genes blaCTX-M-15 e blaCTX-M-9, foi confirmada entre cepas de E. coli isoladas de animais brasileiros, enquanto uma predominância de plasmídeos IncI1 (~200 kb) pertencentes ao complexo clonal (CC) CC12 contendo o gene blaCMY-2 foi observado entre linhagens de E. coli, em filogrupos de baixa virulência A e B1. A presença de plasmídeos do tipo IncHI2 (~ 600kb) carregando o gene blaCTX-M-15 foi confirmada em cepas de E. cloacae ST927 isoladas de fezes e saliva de cães assintomáticos no Brasil. Entre os animais franceses com infecções, os isolados de E. coli pertencentes ao filogrupo A, B1 e B2 apresentaram tamanho de plasmídeo IncF de ~210-290 kb, carregando principalmente genes blaCTX-M-15, além da presença de plasmídeo IncI1 carregando em sua maioria genes blaCTX-M-1, blaCTX-M-9 e blaCMY-2. Em animais franceses saudáveis, além das associações blaCTX-M-15/IncI1, blaCTX-M-1/IncFIB, blaCTX-M-14/IncF e da presença de blaCMY-2 e blaTEM-52b (não tipáveis), foi identificada uma cepa de E. coli carregando um plasmídeo IncL (~60kb) contendo o gene blaOXA-48, sendo esta a primeira descrição desse gene em animais na França. Além disso, os genes blaCTX-M-15, blaCTX-M-2 e blaCTX-M-9 foram localizados no cromossomo em cepas brasileiras e francesas, como observado por Southern blot e Sequenciamento de Nova Geração (NGS). Em resumo, em ambos os países, a prevalência de cepas positivas para a resistência tipo ESBL é grande. Os animais de companhia podem ter um papel importante na disseminação dos genes AmpC e ESBL mediados por plasmídeos. / Companion animals can be reservoirs of Gram-negative bacteria resistant to antibiotics used in human and veterinary medicine. The aim of this study was to investigate the genetic context of plasmid-mediated resistance in Gram-negative bacteria isolated from companion animals in Brazil and France, elucidating the potential role of these animals as asymptomatic carriers. DNA samples, extracted from a collection of ESBL-producing Gram-negative bacteria, were analyzed by PCR-based typing and sub-typing schemes, restriction fragment length polymorphism analysis, S1 nuclease PFGE-based sizing and Southern blot hybridization. Additionally, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates were characterized by PFGE (Pulsed-field Gel Electrophoresis), Multilocus Sequence Typing, phylogenetic grouping and O25b typing. Presence of IncH12 (~600-kb) and IncFIB (~210-290-kp) plasmids carrying blaCTX-M-15 and blaCTX-M-9, respectively, was confirmed among E. coli strains isolated from Brazilian pets, whereas predominance of IncI1 plasmids (~200 kb) belonging to the clonal complex (CC) CC12 and carrying blaCMY-2 gene was observed among E. coli strains of low-virulence phylogrups A and B1. The presence of IncHI2-type (~ 600-kb) plasmids carrying blaCTX-M-15 gene was confirmed in E. cloacae strains ST927 isolated from feces and saliva from asymptomatic dogs in Brazil. Among French diseased companion animals, E. coli isolates belonging to phylogroup A, B1 and B2 were found carrying IncF-type plasmid with size of ~210-290-kb, which harbored mainly blaCTX-M-15 genes. In addition, presence of IncI1 plasmids carrying blaCTX-M-1, blaCTX-M-9 and blaCMY-2 genes was identified. In healthy French animals, besides associations blaCTX-M-15/IncI1, blaCTX-M-1/IncFIB, blaCTX-M-14/IncF, and the presence of blaCMY-2 and blaTEM-52b (non-typable), it was observed an E. coli strain carrying an IncL plasmid (~ 60kbp) containing the blaOXA-48 gene, representing the first description of this gene in a French dog. In addition, blaCTX-M-15, blaCTX-M-2 and blaCTX-M-9 genes were located on the chromosome in Brazilian and French strains, as observed by Southern Blot and New Generation Sequencing (NGS) analysis. In summary, in both countries, the prevalence of positive strains for ESBL-type resistance in cats and dogs is high. Companion animals may play an important role in the dissemination of the plasmid mediated AmpC and ESBL genes.