Indiana University-Purdue University Indianapolis (IUPUI) / Introduction: Bacteremia involving oral bacteria and the systemic inflammatory responses are mechanisms that could causally link oral and systemic diseases. Objective: To use an experimental gingivitis model (EGM) in 2 clinical studies to 1) examine the systemic inflammatory responses to dental plaque, and assess racial differences in these responses; 2) determine whether dental plaque accumulation causes bacteremia and subsequent systemic responses following toothbrushing. Additionally, a laboratory study was conducted to examine the interaction between circulating human neutrophils and Fusobacterium nucleatum. Methods: For both clinical studies, healthy adults, aged 18-31 years, were recruited. In the first study, black and white, males and females participated in a 21-day EGM; in the second study, white adults participated in a 7-day EGM. In both studies, subjects visited the clinic weekly for: 1) measurement of the plaque index (PI) and gingival index (GI); 2) collection of peripheral blood samples to evaluate systemic markers of inflammation. In the second study, to analyze bacteremic episodes during the experimental phase, peripheral blood samples were collected at baseline and at 0.5, 5, and 30 minutes post-toothbrushing. In the laboratory study, interactions between F. nucleatum and circulating neutrophils were examined using a luminol-enhanced chemiluminescence assay. Results: During the experimental phases of both clinical studies, PI and GI increased (p<0.05) with a correlation between PI and GI ≥0.79. In the first study, dental plaque accumulation resulted in a systemic response that manifested as changes (p<0.05) in the level of inflammatory markers, hematologic factors, markers of lipid metabolism, and markers of metabolic change. This systemic response differed between individuals of different gender and race. In the second study, bacteremic episodes and changes in hematologic factors were observed post-toothbrushing during the experimental phase. Activation of neutrophils with F. nucleatum, in the laboratory study, increased the levels of neutrophil chemiluminescence (p<0.05). Conclusions: Overall, the findings of these investigations may shed light on the mechanistic pathways by which oral infection may impose risk for systemic diseases and provide some evidence to support a possible causal association between oral and systemic diseases. The clinical significance of this in systemic inflammatory diseases requires further investigation.

Made available in DSpace on 2018-08-01T21:35:36Z (GMT). No. of bitstreams: 1 tese_12104_12-04-18- Dissertação completa - PÓS BANCA FINAL.pdf: 2165031 bytes, checksum: 166de54425438f1aa2ee476e04f24b8c (MD5) Previous issue date: 2018-03-12 / Staphylococcus aureus é um dos principais patógenos causador de uma gama de infecções tanto nosocomiais quanto comunitárias. Bacteremias são constantes e apresentam altos índices de mortalidade e morbidade e todo o globo. A vancomicina (van) é a terapia empírica para tratamento de infecções por cocos Gram-positivos em pacientes hemodialíticos. Em 1997 surgiram estirpes de S. aureus com suscetibilidade reduzida para van (VISA e hVISA). Estes isolados são associados a falhas terapêuticas por van e recidivas. O objetivo deste trabalho foi caracterizar amostras de S. aureus cultivadas em altas concentrações de van quanto à suscetibilidade e atributos de virulência. Quarenta e uma amostras de S. aureus isoladas de pacientes hemodialíticos com bacteremias (parentais) foram crescidas em 4 a 16 &#956;g/mL de van e reisoladas após este teste, sendo denominadas derivadas. Foram isoladas derivadas de todas as 41 amostras S. aureus. Todas as amostras parentais e derivadas foram suscetíveis à van. A concentração mínima inibitória (CMI) de van nas amostras derivadas apresentou um aumento em relação as parentais, porém, dentro dos parâmetros de suscetibilidade pelo Clinical & Laboratory Standards Institute (CLSI). Vinte e quatro pulsotipos foram identificados através da técnica de PFGE e nove amostras (22%) apresentaram resistência à meticilina através do disco de cefoxitina e amplificação do gene mecA. Nove amostras derivadas isoladas em 16 µg/mL de van conseguiram crescer na presença de 8 µg/mL de van. A produção de biofilme e de cinco enzimas hidrolíticas foi menor nas amostras derivadas. A virulência das estirpes derivadas foi avaliada em modelo in vivo com Galleria mellonella, sendo que duas amostras derivadas apresentaram diminuição e uma aumento da virulência. Não houve diferença entre parentais e derivadas quanto a autólise, produção de &#948;-hemolisina, ligação ao fibrinogênio e viabilidade metabólica. Apesar de crescerem em concentrações altas de van as estirpes derivadas apresentaram crescimento lento e CMI na faixa de suscetibilidade, indicando tolerância. De todos os fatores de virulência testados a pressão seletiva com van afetou apenas a produção de biofilme e cinco enzimas hidrolíticas. No modelo in vivo a virulência das derivadas foi variada, indicando que ser estirpe-dependente.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (M.Sc. (Clinical Tropical Medicine))--Mahidol University, 2000.

Made available in DSpace on 2016-08-29T15:34:59Z (GMT). No. of bitstreams: 1 tese_8770_DISSERTAÇÃO MICHEL - DOC. FINAL .pdf: 2273236 bytes, checksum: 48fed602f2e1839962db028aacc9ea3d (MD5) Previous issue date: 2015-04-17 / A vancomicina (van) é empiricamente prescrita para o tratamento de infecções por estafilococos em pacientes submetidos à hemodiálise (HD). O monitoramento das concentrações séricas mínimas (CSM) de van é utilizado como o mais preciso e prático método para se estimar sua eficácia, sendo recomendada a manutenção das CSM entre 10 e 20 µg/mL. O objetivo deste trabalho foi investigar as CSM de van de pacientes sob HD, em um período de dois anos e correlacioná-los com a concentração inibitória mínima (CIM) deste glicopeptídeo para Staphylococcus spp recuperados de bacteremias nestes mesmos indivíduos. As amostras recuperadas (N=80) foram testadas quanto à CIM (diluição em ágar ou caldo) de van, gentamicina (gen), oxacilina (oxa), tetraciclina (tet), rifampicina (rif), ciprofloxacino (cip), penicilina G (pen) e daptomicina (dap). Foram coletadas 101 amostras de soro de 22 pacientes em regime de administração de 1g a cada 4-5 dias, mais gen (1,5-2,0 mg/Kg) ao final de cada HD. As amostras foram coletadas antes de cada sessão de HD, nos tempos de 0, 48, 72, 96 e 120 horas após a infusão do fármaco. As CSM de van foram obtidas pelo imunoensaio de micropartículas quimioluminescentes (CMIA). Doseamento microbiológico de van foi realizado por meio da técnica pourplate com ágar sais mínimos. S. aureus foi a espécie mais frequentemente isolada (24%), seguida de Staphylococcus spp coagulase negativa (ScoN) (15%). Maiores taxas de resistência ocorreram para oxa (17% e 58%), pen (85% e 84%) e cip (26% e 45%) em S. aures e ScoN, respectivamente. Das amostras de sangue coletadas, 77,8% exibiram concentrações séricas de van <10 µg/mL e considerando apenas as coletadas imediatamente antes da próxima dose de van (CSM), 90,6% também continham concentrações inferiores àquelas recomendadas para efetiva atividade antiestafilocócica. Os valores de concentrações séricas de van obtidas pelo bioensaio apresentaram ótima correlação com o CMIA (padrão ouro) (R2 = 0,96), com valores estatísticamente similares (p<0,05) quando aplicado o fator de correção. A prevalência de Staphylococcus spp resistente à oxa sustenta o uso empírico de van, contudo, a alta taxa de isolados de S. aureus que exibiram CIM de van de 1 µg/mL (59,5%) associada às baixas CSM de van a que são submetidos a maioria dos pacientes indica chance de falha terapêutica e seleção de cepas resistentes. Assim, uma abordagem terapêutica individualizada e monitoramento da droga devem ser considerados. Para tanto foi validado o ensaio microbiológico que, pelo baixo custo e simplicidade da técnica facilita a implementação do monitoramento de van na rotina de laboratórios clínicos de pequeno porte.

A 67-years-old male presented with periumbilical abdominal pain, fever and jaundice. His anaerobic blood culture was positive for clostridium perfringens. Computed tomogram scan of the abdomen and abdominal ultrasound showed normal gallbladder and common bile duct (CBD). Subsequently magnetic resonance cholangiopancreaticogram showed choledocholithiasis. Endoscopic retrograde cholangiopancreaticogramwith sphincterotomy and CBD stone extraction was performed. The patient progressively improved with antibiotic therapy Choledocholithiasis should be considered as a source of clostridium perfringens bacteremia especially in the setting of elevated liver enzymes with cholestatic pattern.

Background: The incidence of Pseudomonas aeruginosa bacteremia has not been defined in a population-based investigation. Methods: We performed a retrospective, population-based incidence study using resources of the Rochester Epidemiology Project of Olmsted County, Minnesota. We identified all Olmsted County residents with P. aeruginosa bacteremia between January 1, 1997, and December 31, 2006, by microbiology records in the only 2 laboratories in the county. Medical records were reviewed to confirm diagnosis, residency status, and clinical characteristics. Results: Age-adjusted incidence per 100,000 person-years was 10.8 (95% confidence interval [CI], 7.5-14.0) in men and 3.7 (95% CI, 2.2-5.2) in women for total P. aeruginosa bacteremia, and 8.4 (95% CI, 5.5-11.2) in men and 2.5 (95% CI, 1.3-3.8) in women for monomicrobial P. aeruginosa bacteremia. There was no significant change in incidence of total P. aeruginosa bacteremia during the past decade (P = .418). Incidence increased exponentially with age, with a greater magnitude of increase in men compared with women for total and monomicrobial P. aeruginosa bacteremia (P = .007 and P = .015, respectively). In patients with monomicrobial P. aeruginosa bacteremia, the median age was 69 years, and 78.4% of cases were either nosocomial or health care associated. Most patients had multiple comorbid conditions. The urinary tract was the most common primary source of infection. The 28-day all-cause mortality of monomicrobial P. aeruginosa bacteremia was 25.5%. In vitro susceptibility to ciprofloxacin was 95.3%. Conclusion: To our knowledge, this is the first population-based incidence study of P. aeruginosa bacteremia. The incidence of P. aeruginosa bacteremia has remained stable during the past decade. Fluoroquinolone susceptibility is high among local P. aeruginosa bacteremia isolates.

Aeromonas salmonicida is associated with superficial skin infections in fish. Its virulence factors allow colonization of water including surface water such as salt water, beaches, and fresh water wells. Moreover, it is possible for immunocompromised patients to develop invasive disease after chronic exposure to Aeromonas spp.Through contaminated water. While there are reports of Aeromonas spp. bacteremia following water ingestion, there have been no reports of A. salmonicida bacteremia from water consumption. We report the first case of A. salmonicida bacteremia in a patient with diabetes due to chronic consumption of well water.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第20624号 / 社医博第82号 / 社新制||医||9(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 木原 正博, 教授 古川 壽亮, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Background This study assessed the impact of infectious diseases consultation (IDC) on 30-day readmission rates in patients with Staphylococcus aureus bacteremia (SAB). Furthermore, this study also evaluated the effect of IDC on adherence to guideline-directed therapy. Methods This retrospective cohort study enrolled 149 adult patients with SAB. Cohort 1 included 28 patients without IDC. Cohort 2 included 121 patients with IDC. Primary end point was all-cause 30-day readmission rates. Secondary outcomes included adherence to guideline-directed therapy and hospital length of stay (LOS). Guideline-directed therapy included repeat blood cultures until blood sterility, assessment for an echocardiogram, and appropriateness of antimicrobial therapy (including antibiotic, dose, and duration). Results Readmission rates were 46.4% (13/28) without IDC and 19% (23/121) with IDC (P = 0.006). Guideline-directed therapy occurred in 21.4% (6/28) without IDC versus 96.7% (117/121) with IDC (P = 0.0001). The average LOS was shorter without IDC than with IDC (5.6 vs 7.8 days, respectively; P = 0.01). The most common reasons for lack of guideline adherence in the control group were lack of echocardiogram (72.4%) and lack of repeat blood cultures (51.7%). Multivariate analysis demonstrated that only lack of IDC significantly affected readmission rates (odds ratio, 3.51; 95% confidence interval, 1.48-8.52; P = 0.0048). Conclusions Consultation with infectious diseases reduces 30-day readmission rates in patients with SAB and increases adherence to guideline-directed therapy; however, LOS was increased. Infectious diseases consultation should be considered for all patients with SAB.