http://www.bdtd.uerj.br/handle/1/3562 2026-09-11T23:45:32Z 2026-09-11T23:45:32Z Motta, Isabelle Christine de Moraes http://www.bdtd.uerj.br/handle/1/26038 2026-08-24T17:29:43Z 2026-04-28T00:00:00Z

Título: Aspectos epidemiológicos e do perfil de resistência de agentes antimicrobianos de amostras de Staphylococcus coagulase-negativo isoladas de hemoculturas de pacientes hospitalizados na região metropolitana do Rio de Janeiro Autor: Motta, Isabelle Christine de Moraes Primeiro orientador: Mattos-Guaraldi, Ana Luíza de Abstract: Coagulase-negative Staphylococcus (CoNS) have gained increasing relevance as etiological agents of healthcare-associated infections due to the expanded use of medical devices, prolonged hospitalizations, and the growing prevalence of antimicrobial resistance. Their ability to adapt and persist in clinical environments is notable, particularly through biofilm formation and their potential role as important reservoirs of antimicrobial resistance genes. The increasing frequency of strains resistant to methicillin and other widely used antimicrobials reduces available therapeutic options and negatively impacts clinical outcomes. This study aimed to evaluate the epidemiological aspects and antimicrobial resistance profiles of coagulase-negative Staphylococcus isolates obtained from blood cultures of hospitalized patients in the metropolitan region of Rio de Janeiro. Species identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility profiles were determined using the disk diffusion method and by measuring the minimum inhibitory concentration (MIC) of vancomycin. In addition, the presence of the mecA gene was investigated in all isolates using polymerase chain reaction (PCR), and the blaZ gene was detected by PCR in Staphylococcus hominis and Staphylococcus warneri strains. Overall, the findings suggest a significant level of antimicrobial resistance among CoNS isolates. However, no resistance to vancomycin was detected, indicating that this antimicrobial remains a fundamental option for the treatment of severe infections caused by CoNS. Understanding the multifactorial aspects of antimicrobial resistance in CoNS is essential for optimizing patient management and ensuring the most appropriate therapeutic strategies in clinical practice. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação

2026-04-28T00:00:00Z Nascimento, Letícia da Silva http://www.bdtd.uerj.br/handle/1/25930 2026-08-10T19:31:49Z 2025-12-17T00:00:00Z

Título: Um patógeno de duplo risco: detecção de genes relacionados à hipervirulência em cepas de Klebsiella pneumoniae produtoras de carbapanemase KPC Autor: Nascimento, Letícia da Silva Primeiro orientador: Carvalho-Assef, Ana Paula D’Alincourt Abstract: Klebsiella pneumoniae is a Gram-negative bacillus in which classical strains (cKp) are primarily associated with healthcare-associated infections (HCAI) and exhibit high levels of antimicrobial resistance, whereas hypervirulent strains (hvKp), traditionally linked to community-acquired infections, are characterized by an enhanced ability to invade tissues and evade the host immune response. The emergence of convergent lineages that combine multidrug resistance with hypervirulence markers represents a growing challenge, increasing infection severity and limiting therapeutic options. In Brazil, studies addressing convergent strains remain scarce. This study aimed to detect, by PCR, genes related to hypervirulence (iucA, iroB, peg-344, rmpA and rmpA2) and extended-spectrum β-lactamase (ESBL) (blaSHV, blaTEM, and blaCTX-M), as well as to evaluate antimicrobial susceptibility (cefiderocol and ceftazidime/avibactam) and clonal diversity using PFGE in 152 clinical isolates of K. pneumoniae carrying blaKPC, obtained from the LabSUR/Fiocruz collection between 2020 and 2024. Isolates were identified by MALDI-TOF MS, and the hypermucoviscous phenotype was assessed using the string test, with 17 positive isolates being found. Among the 152 isolates, 15.1% (n=23) carried at least one gene associated with hypervirulence. Subsequent analyses were conducted with these 23 isolates. The rmpA gene was the most prevalent (12.5%, n=19), followed by rmpA2 (8.7%, n=2) and wcaG (n=1); one isolate simultaneously carried rmpA and wcaG. The string test was positive in only 2 (8.7%) of the 23 isolates, indicating that the hypermucoviscous phenotype does not necessarily correlate with the genetic markers evaluated. All isolates carried blaSHV, while blaTEM and blaCTX-M were detected in 56.5% (n=13) and 39.1% (n=9), respectively, demonstrating the coexistence of hypervirulence-associated determinants and β-lactam resistance. Although no resistance to cefiderocol was observed, 14.7% (n=4) of the isolates exhibited resistance to ceftazidime-avibactam. PFGE analysis revealed 19 clonal groups, indicating the circulation of multiple K. pneumoniae lineages with convergent virulence and resistance profiles. Whole-genome sequencing revealed mutations and genes associated with resistance to several antimicrobial classes, as well as various virulence genes and additional hypervirulence markers, such as iroE and iutA, present in all isolates (n=23), in addition to a predominance of ST11 (34.78%, n=8). All isolates carried blaKPC-2, a widely disseminated and well-documented variant. The simultaneous identification of genes associated with hypervirulence and resistance in blaKPC-positive isolates confirms the presence of CR-hvKp strains, suggesting that convergent lineages may already be circulating in Brazil in a subdiagnosed manner. Furthermore, because these strains often infect debilitated patients, they may not raise clinical suspicion of hypervirulence, facilitating their silent dissemination. This scenario is particularly concerning, as these lineages have the potential to cause severe and invasive infections in individuals without comorbidities, with limited therapeutic options. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação

2025-12-17T00:00:00Z Durão, César Vieira http://www.bdtd.uerj.br/handle/1/25566 2026-04-01T20:13:40Z 2026-04-04T00:00:00Z

Título: Avaliação da influência da obesidade materna no desenvolvimento de resposta humoral no baço da prole em modelo experimental murino Autor: Durão, César Vieira Primeiro orientador: Silva, Flávia Márcia de Castro e Abstract: INTRODUCTION: The increase in maternal obesity cases has raised significant concern, as it is associated with a higher overall mortality rate and represents a major risk factor for several diseases. During pregnancy, this condition can trigger metabolic changes that influence fetal development, impacting various systems, including the immune system. OBJECTIVE: This study aimed to evaluate the influence of maternal obesity on the development of the humoral immune response in the offspring’s spleen. METHODS: A murine experimental model using BALB/c mice was employed. Females were subjected to a high-fat diet (60% of calories derived from fat) for ten weeks and subsequently mated. Offspring were selected at different ages (1, 3, 7, and 24 days of life) for experimental procedures, in which the spleen and serum were collected for analysis of cell phenotypes by flow cytometry, histology, and detection of antibody isotypes by ELISA. RESULTS: Flow cytometry analyses revealed differences in the frequency of cell groups and in the membrane molecule expression of splenic cells. On the first day of life, an increase in B lymphocytes and a reduction in CD19⁺CD138⁺ plasma cells were observed in offspring from obese mothers compared to the control group. On the seventh day, there was an increase in B lymphocytes and MHCII expression in these cells, along with a reduction in CD19⁺CD138⁺IgG2a⁺ plasma cells and T lymphocytes expressing CXCR5. By the twenty-fourth day of life, B lymphocytes, plasma cells, and T lymphocytes were increased; however, MHCII and PD-L1 expression was reduced in CD19⁺ cell populations. Additionally, histological evaluation showed a greater number of lymphoid follicles and a lower eosinophil count in the offspring of obese mothers. A reduction in serum immunoglobulin isotypes IgM and IgG was detected in these animals, although an increase in IgG1 and IgG2a isotypes was observed in the more developmentally advanced group. CONCLUSION: The results demonstrate that maternal obesity affects the development of the humoral immune response in the offspring, compromising immune activation. The reduction of T lymphocytes and the low serum levels of IgG and IgM suggest impairments in class switching and immunological memory. These changes may result in a less efficient immune response, potentially leading to more prolonged infections. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação

2026-04-04T00:00:00Z Rosa, Heloisa da Silva http://www.bdtd.uerj.br/handle/1/25501 2026-03-19T20:57:50Z 2023-12-12T00:00:00Z

Título: Tipificação molecular e análise da resistência aos antimicrobianos em Acinetobacter spp. recuperados do período pré-pandêmico e pandêmico da COVID-19 Autor: Rosa, Heloisa da Silva Primeiro orientador: Marques, Elizabeth de Andrade Abstract: Acinetobacter spp. are nosocomial pathogens that present a significant public health challenge due to their ability to resist disinfection and desiccation, primarily attributed to the rising incidence of multidrug-resistant strains, thereby limiting therapeutic options. Throughout the COVID-19 pandemic, Acinetobacter spp. emerged as a prominent pathogen linked to secondary infections, resulting in prolonged stays in the ICU and heightened patient mortality. Therefore, this study aims to evaluate the antimicrobial resistance profile, its correlation with carbapenemase enzyme production, and the phylogenetic relationships among 60 Acinetobacter spp. samples retrieved from patients hospitalized at a university hospital in Rio de Janeiro during both the pre-pandemic and pandemic phases of COVID-19. Antimicrobial susceptibility tests were conducted using agar diffusion and broth microdilution methods. The detection of carbapenemase production was performed using the modified carbapenem inactivation method (mCIM) and the NG-TEST CARBA 5 immunochromatographic assay. The determination of the phylogenetic relationships among isolates was carried out using pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing (WGS) of selected samples was performed to identify the species, determine the sequence type (ST), and detect polymyxin B resistance determinants. Out of the 60 samples tested, 58.3% (n = 35) exhibited resistance to all tested antimicrobials. Only one isolate displayed a multidrug-resistant (MDR) phenotype, and 95% (n = 57) demonstrated extensively drug-resistant (XDR) profiles. Minimum inhibitory concentration values for polymyxin B ranged from 0.25 to 4µg/mL. Through the mCIM, 52 carbapenemase-producing isolates were detected, and through the NG-TEST CARBA 5, 20 isolates were found to produce the IMP carbapenemase. Thirty-six pulsotypes were identified, with pulsotype L being the most prevalent, comprising ten isolates. WGS of isolates 22319 and 22718 was conducted due to polymyxin B resistance and susceptibility to other tested antimicrobials. The analysis of WGS data revealed that both isolates were identified as Acinetobacter nosocomialis, with 22319 associated with ST 395 and 22718 with the new ST 2261, characterized in this study. These isolates did not belong to any clonal complex. Both isolates exhibited mutations in the lpsB, lpxC, and lptD genes, while 22718 also displayed mutations in lpxD and pldA, potentially linked to polymyxin B resistance. The mcr gene was not detected. These results signify a widespread epidemiological profile in Brazil and worldwide, where the high rate of antimicrobial resistance and the presence of carbapenemases are alarming. Further studies are imperative to formulate measures for the control and prevention of healthcare-associated infections caused by these microorganisms. Additionally, polymyxin B resistance may be associated with mutations in the lpsB, lpxC, lpxD, lptD, and pldA genes; however, additional studies are required to comprehend the significance and contribution of these mutations to polymyxin B resistance. Instituição: Universidade do Estado do Rio de Janeiro Tipo do documento: Dissertação

2023-12-12T00:00:00Z