No abstract available. / Thesis (M.D.)-University of KwaZulu-Natal, 2004.

iv The present work describes the evaluation of the value of polymerase chain reaction in diagnosis of pneumonia caused by the most common three bacterial pathogens / Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis from sputum of patients with community acquired pneumonia admitted to The Department of Pulmonary Diseases of Gulhane Military Medical Academy. In this study, 107 sputa from 142 patients with suspected community acquired pneumonia were used to survey the causative agents. Identification of the pathogens was performed by sputum Gram stain and conventional microbiological methods. Polymerase chain reaction was performed to investigate the presence of S.pneumoniae, H.influenzae, and M.catarrhalis for the same sputum samples as well. PCR products were processed by electrophoresis on 2% agarose gels with visualization of the amplicon with ethidium bromide and UV illumination. The 33 of 107 samples were positive in cultures and 67 in PCR. S.pneumoniae (48.5%) was the most common etiologic agent as to PCR analysis. The incidences of H.influenzae and M.catarrhalis were determined as 18.6%, and 4.7% respectively. The incidence of S.pneumoniae in patients with CAP and control group individuals were almost the same. The sputum PCR positives were higher than those reported carriage rates for these three microorganisms. 9 of 107 patients with PCR-positive had evidence of infection with pathogens other than S.pneumoniae. The results indicated that some of the PCR results were false positive due to oropharyngeal contamination. PCR testing of sputum samples for diagnosing pneumococcal pneumonia is unable to distinguish colonization from infection in some circumstances. To distinguish the colonization from infection, sputum Gram stain should be applied to the sputum specimens. Because of being faster and easier, PCR looks like becoming more reliable technique by the using of valid specimens from patients with community-acquired pneumonia if supported by quantitative techniques.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-08-29T19:42:59Z No. of bitstreams: 1 Sara Lacerda Almeida Sant anna. Epidemiologia da pneumonia infantil em uma comunidade de SalvadorBA.pdf: 753919 bytes, checksum: 5aa3e2124780501390e8191fa658803e (MD5) / Made available in DSpace on 2012-08-29T19:42:59Z (GMT). No. of bitstreams: 1 Sara Lacerda Almeida Sant anna. Epidemiologia da pneumonia infantil em uma comunidade de SalvadorBA.pdf: 753919 bytes, checksum: 5aa3e2124780501390e8191fa658803e (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / As Infecções Respiratórias Agudas (IRA), principalmente a pneumonia, constituem um importante problema de saúde pública contribuindo com altas taxas de morbidade. e mortalidade no mundo principalmente nos países em desenvolvimento. O objetivo deste trabalho foi caracterizar a infecção do trato respiratório inferior e estimar a incidência de pneumonia em crianças menores de cinco anos atendidas na unidade de emergência de São Marcos, em Pau da Lima, Salvador-Bahia, bem como identificar os principais fatores de risco associados à aquisição desta doença. No período de Junho de 2008 a Maio de 2009, um total de 2.542 crianças foram incluídas no estudo. Cerca de 55,1% eram do sexo masculino; 58,8% eram menores de dois anos de idade; 64,7% eram mulatos. Raio-X de tórax foi realizado na maioria das crianças (93%). Pneumonia foi diagnosticada em 41,9% das crianças. Hospitalização ocorreu em 37,8% dos casos diagnosticados com pneumonia. Considerando apenas as crianças moradoras na área de estudo da coorte de Pau da Lima, pode-se calcular a taxa de incidência de pneumonia em crinças menores de 5 anos, a qual foi de 38,4 por 1.000 habitantes. Dentre os fatores de risco investigados para pneumonia, identificamos que as crianças que frequentam creche/escola, crianças que convivem com menores de 15 anos em casa e crianças que têm contato com fumantes no domicílio tiveram chance maior de desenvolver a doença (p<0,001). Os principais antibióticos utilizados no tratamento foram amoxicilina e penicilina. Nenhum óbito foi registrado durante este período. Nosso estudo indica que a pneumonia exerce um grande impacto na morbidade, sugerindo que a conduta diagnóstica e tratamento precoce são fundamentais e importantes no impacto da mortalidade por este agravo. Nossa investigação fornece uma linha de base para futuras avaliações sobre este agravo, bem como o impacto da vacina neste grupo populacional. / The Acute Respiratory Infections (ARI) especially pneumonia, are an important public health problem contributing to high rates of morbidity and mortality worldwide especially in developing countries. The aim of this study was to characterize the lower respiratory tract infection and estimate the incidence of pneumonia in children under five years of age at the emergency department of San Marcos in Pau da Lima, Salvador, Bahia, as well as identify risk factors associated with acquisition of this disease. In the period of June 2008 to May 2009, a total of 2542 children were included in the study. About 55.1 % were male, 58.8% were under two years old, 64.7% were mulatto. Chest X-ray was performed in most of children (93%). Pneumonia was diagnosed in 41.9%. Hospitalization occurred in 37.8% of patients diagnosed with pneumonia. Considering only children living in the area of a cohort study of Lima, was possible to calculate the incidence rate of pneumonia comprised children younger than 5 years, which was 38.4 per 1,000 inhabitants. Among the investigated risk factors for pneumonia, we identified that children who attend day care / school, live with other children under 15 years at home and have contact with smokers at home, had a chance of developing the disease (p <0.001). The main antibiotics used in treatment were amoxicillin and penicillin. No death was reported during this period. Our study indicates that pneumonia has a major impact on morbidity, suggesting that the diagnostic and early treatment are essential and important impact on mortality from this disease. Our research provides a baseline for future evaluations of this offense, and the impact of the vaccine in this population group.

Background: Community acquired pneumonia causes 5,9% of deaths in elderly South Africans. Mortality rates are increased in those in whom initiation of therapy with an appropriate agent has been delayed. Whereas Mycoplasma pneumoniae and Legionella pneumophila are sensitive to the macrolides or tetracycline, they do not respond to the currently recommended first-line agents for community acquired pneumonia, penicillin or a cephalosporin. It was therefore necessary to assess the prevalence of exposure to these 2 organisms in the elderly in order to determine whether a modification in the recommendations may be justified. Methods: Study population and survey: Subjects were residents of 4 old age homes in Cape Town who were older than 60 years and willing to participate. Written consent was obtained, a demographic and medical history questionnaire was completed, and a sample of blood was drawn. Laboratory methods: The indirect fluorescent antibody tests (Zeus Scientific Inc, New Jersey, USA) were used to detect the presence of antibodies to Mycoplasma pneumoniae and Legionella pneumophila. Results: The participation rate in this study was high, with 88,4% (677/766) taking part. Seropositivity for both of these organisms was low. There were 17 participants (2, 51 %) with antibodies to mycoplasma (IgG only in 8, IgM only in 1, and both IgG and IgM in the remaining 8). Titres were low with only 1 IgM titre of 16, and only 3 IgG titres of 64. Antibodies to Legionella were demonstrated in only 9 participants (1,33%). All these titres were 128 or above. Conclusions: It is concluded that first-line therapy for community acquired pneumonia should adhere to the current guidelines published by the South African Pulmonology Society. There is no indication for the routine use of agents active against Legionella or mycoplasma. Clearly, these antibiotics should be introduced if specific pointers to infection with one of these organisms are found. Because of the low seropositivity rate, the indirect fluorescent antibody test for these 2 agents has a high specificity in this population. This may be of use in making a diagnosis in an acute infection Further studies are required to elucidate the immunological response to these organisms in elderly persons. A further survey should be done to determine the seropositivity rate to these agents in community dwelling elderly.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第20288号 / 社医博第77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 川上 浩司, 教授 一山 智, 教授 伊達 洋至 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DGAM

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious public health problem nationwide, threatening to develop into an epidemic. Many of these patients are presenting to their primary care clinics with skin and soft tissue infections (SSTIs). The CDC has reported that in 2005, MRSA was responsible for an estimated 94,000 life-threatening infections and 16,650 deaths. The purpose of this study is to estimate the incidence of CA-MRSA within a specific family practice in Florida and to identify epidemiologic factors, classify antibiotic susceptibility patterns, and evaluate patient education in regard to disease management and prevention. This study was a descriptive, epidemiologic, three-year retrospective medical record review of all wound cultured skin and soft tissue infections that presented to a family practice between January 2007 and December 2009. Sixty-two medical records met the inclusion and exclusion criteria for the study. Of these 62 SSTIs, 44 cultures grew one or more bacterial organisms. The incidence of CA-MRSA was 66% (n=29). The mean age of those with CA-MRSA was 40 years old, with a range from 7 to 90 years old. Sixty-two percent (n=18) were male and 38% (n=11) were female; additionally 69% (n=20) lived within a 10 mile radius from the family practice, while 31% (n=9) lived in a surrounding suburb. The most frequent race was Caucasian 83% (n=24), with African American at 10% (n=3) and Hispanics 7% (n=2). Risk factors associated with CA-MRSA was obesity 41% (n=10), diabetes mellitus 24% (n=7), and a previous history of MRSA infection 24% (n=7). Skin and soft tissue infections were diagnosed as either an abscess 62% (n=18), boil 24% (n=7), pustule 10% (n=3), or cellulitis 4% (n=1). CA-MRSA isolates were susceptible to trimethoprim-sulfamethoxazole 100% (n=29), doxycycline 93% (n=27), and rifampin 100% (n=14). Clindamycin susceptibility was 65% (n=15) with resistance at 30% (n=7) and 5% (n=1) intermediate. Both cephalexin and erythromycin were 100% resistant. Documentation in the medical record on wound care was found in 45% (n=13) of the records. The incidence of CA-MRSA SSTI was 66%, which identifies this suburban community at high risk for this bacterial infection. Risk factors associated with CA-MRSA included obesity (BMI > 30), history of previous MRSA infection, and diabetes mellitus. There were no clinical characteristics that helped distinguish MRSA infection from other bacterial SSTIs. Most SSTI were treated with incision and drainage and a susceptible antibiotic. Judicious use of antibiotics not only provides appropriate treatment, but is also critical in prevention of antibiotic resistance. Lastly, patient education in adequate hygiene is essential in preventing the spread of CA-MRSA

A review of literature related to community-acquired Clostridium difficile- associated disease (CA-CDAD) was conducted. Information was collected from Cumulative Index to Nursing and Allied Health (CINAHL) and MEDLINE-EBSCOhost databases. Clinical practice recommendations were obtained from the CDC. Studies were examined for epidemiology of infection due to C. difficile in the community and interventions to reduce transmission. Findings demonstrated a mirroring of to CA-CDAD to community-acquired Methicillin-resistant Staphylococcus aureus (MRSA). Multiple studies found underlying gastrointestinal disorders and use of cephalosporin antibiotics to be a risk factor. Another identified risk factor was use of gastric acid suppressive drugs. Also, no particular C. difficile strain was more likely to cause recurrence. Many positive cases for CA-CDAD lacked traditional risk factors such as recent antibiotic exposure. To reduce transmission of community-acquired MRSA the CDC recommends MRSA should be considered in the differential diagnosis of soft skin tissue infections. Clinicians should also collect specimens for culture and antimicrobial susceptibility testing from all patients with abscesses. The CDC recommends clinicians should teach their patients to limit transmission and ask about similar cases in household members and close contacts. Therefore, to reduce transmission of CA-COAD, Clostridium difficile- associated disease should be considered in the differential diagnosis of diarrhea. Clinicians should collect specimens for culture based on patient history & current clinical presentation for patients with diarrhea. It is important that patients be taught the proper hygiene and cleaning protocols to reduce transmission

[pt] A Organização Mundial da Saúde declarou que a resistência aos antibióticos é uma das 10 principais ameaças globais à saúde pública. Entre os fatores que causam a disseminação de bactérias multirresistentes está o uso excessivo de antibióticos em hospitais. Esta tese baseia-se na premissa de que é necessário usar dados históricos para melhorar a prescrição de antibióticos e, assim, reduzir o impacto da resistência em ambientes hospitalares. Seus objetivos específicos incluem a análise de dados para fornecer informações que possam apoiar a prescrição de antibióticos, evitando assim que as taxas de resistência permaneçam elevadas após a pandemia de COVID-19 e prevenindo futuras quebras de protocolo semelhantes.. A tese também investiga as diferenças de desfechos entre a apresentação de bactérias resistentes e não resistentes em infecções adquiridas na comunidade. Para alcançar esses objetivos, os métodos incluem ferramentas de análise de dados, como estatísticas descritivas e inferenciais, Regressão Logística, Mineração de Processos e Mineração de Texto. Os dados incluem informações sobre pacientes internados em Unidades de Terapia Intensiva em hospitais de uma rede privada localizados no Rio de Janeiro, Brasil. A tese é composta por três artigos e descreve ainda uma plataforma desenvolvida para apoiar a prescrição de antibióticos em hospitais. Os resultados da tese revelaram um aumento significativo no consumo de antibióticos durante a pandemia, especialmente durante o segundo e terceiro meses da doença no Brasil. Esse aumento, aliado à alta variabilidade nos tratamentos de pacientes com COVID-19, demonstra que a incerteza em relação à doença levou ao não cumprimento dos protocolos previamente estabelecidos. O meropenem, um antibiótico da classe dos carbapenêmicos, teve o maior número ajustado de doses prescritas para pacientes com COVID-19 nos hospitais analisados. O aumento na prescrição de carbapenêmicos provavelmente explica o aumento observado na resistência a esse antibiótico durante o surto de COVID-19. No período pós-surto, a taxa de resistência aos carbapenêmicos diminuiu, seguindo a queda no consumo desses antibióticos após os primeiros meses da pandemia. No entanto, mesmo com a diminuição, os níveis de resistência pós-surto permaneceram mais altos do que antes da pandemia. Além disso, observou-se que a pandemia alterou outro hábito dos médicos nos hospitais pois o número de exames por paciente aumentou durante a pandemia e, mesmo após o surto da doença, continuou mais alto do que antes da doença. A tese também demonstrou como ferramentas de Mineração de Texto podem ser utilizadas na etapa de tratamento dos dados, possibilitando a inclusão de mais informações nas análises. Constatou-se ainda que, embora um terço dos pacientes admitidos em unidades de terapia intensiva apresentassem bactérias resistentes, não houve evidência de que isso implicasse em maiores chances de mortalidade hospitalar ou sepse em comparação com pacientes com infecções comunitárias por bactérias não resistentes. / [en] The World Health Organization has declared that antimicrobial resistance is one of the top 10 global public health threats facing humanity. Among the factors that cause the dissemination of multidrug-resistant bacteria is the overuse of antimicrobials in hospitals. This thesis is based on the premise that it is necessary to use historical data to improve antimicrobial prescription and thus reduce the burden of antimicrobial resistance in hospital settings. Its specific goals include analyzing data to provide information that can support antimicrobial prescription, thus avoiding antimicrobial resistance rates remaining high after the COVID-19 pandemic and preventing future similar protocol breakdowns. It also investigates the differences in outcomes between presenting resistant vs. non-resistant bacteria in community-acquired infections. To achieve these objectives, the methods include data analysis tools such as descriptive and inferential statistics, Logistic Regression, Process Mining, and Text Mining. The data includes information on patients admitted to Intensive Care Units in hospitals from a private network located in Rio de Janeiro, Brazil. The thesis comprises three articles and describes a CDSS developed to support antimicrobial prescription in hospitals. The thesis s findings revealed a significant increase in antimicrobial consumption and high variability in treatments for COVID-19 patients. Specifically, meropenem, a carbapenem-class antimicrobial, presented the highest adjusted number of doses prescribed for COVID-19 patients in the analyzed hospitals. The escalation in carbapenem prescription probably explains the observed increase in carbapenem resistance during the COVID-19 surge. In the post-surge, the carbapenem resistance rate decreased, following the decrease pattern we found in carbapenem consumption after the first months of the pandemic. Even though there was a decrease in carbapenem resistance, the post-surge levels remained higher than before the surge. Besides, this thesis did not find an association between presenting with antimicrobial-resistant bacteria and higher chances of hospital mortality or sepsis in patients with community-acquired infections.

Récemment, les microbiotes pulmonaires bactériens d’un nombre très limité de patients atteints de mucoviscidose et de pneumopathies acquises sous ventilation mécanique (PAVM) ont été étudiés en utilisant l'amplification du gène 16S rDNA bactérien suivie par la construction de librairies de clones et différentes approches de séquençage. Ces études ont montré que la population microbienne de patients atteints de maladies respiratoires était plus diversifiée que prévue. Dans l'étude actuelle, nous utilisons une approche comparable pour identifier exhaustivement les agents pathogènes (bactéries, virus, et champignons) composant le microbiote pulmonaire associé aux pneumopathies développées en unités de réanimation. L'étude a inclus des patients admis en réanimation et présentant des formes de pneumopathies acquises sous ventilation mécanique (n = 106), de pneumopathies communautaires (n = 32), de pneumopathies nosocomiales sans ventilation mécanique (n = 22) et de pneumopathies d’aspiration (n = 25). Une cohorte de 25 patients admis en réanimation et ne présentant pas de symptômes de pneumopathie a été étudiée comme contrôle. Cette première partie du travail amènera ainsi à réaliser un catalogue exhaustif des agents de pneumopathies nosocomiales ; à connaître la prévalence des agents identifiés et d’identifier les co-infections fréquemment observées, et surtout à vérifier si ces agents peuvent être identifiés ou pas dans les prélèvements respiratoires profonds de patients non symptomatiques. Pour réaliser cette partie du travail, des séries de prélèvements, incluant des prélèvements de lavage broncho-alvéolaire (LBA), des prélèvements de sang et d'urine ont été étudiés. Ces prélèvements ont été testés par des moyens d’identification moléculaire moderne basés sur l’amplification de gènes conservés (gènes16S rDNA des bactéries et gène 18S rDNA des champignons) suivie par clonage et séquençage à grande échelle. D’autres pathogènes atypiques sont ciblés par des tests de PCR avec utilisation d’amorces spécifiques. Nous avons également inclus la culture, la co-culture d’amibes, la détection sérologique d'anticorps dirigés contre des agents sélectionnés et des tests d'antigène urinaire, afin de comparer ces tests de routine aux approches moléculaires. Comme résultats, les tests moléculaires nous ont permis d’identifier un vaste répertoire de 160 espèces bactériennes dont 73 n'ont jamais été précédemment rapportées à l’étiologie des pneumopathies. En outre, nous avons trouvé 37 phylotypes bactériens potentiellement nouveaux. Nous avons également identifié 24 espèces de champignons dont 6 n'ont pas été précédemment rapportées à l’étiologie des pneumopathies, 7 virus et étonnamment 6 espèces de plantes. De plus, certains agents pathogènes considérés comme typiques aux pneumopathies nosocomiales tels que Pseudomonas aeruginosa et des Streptococci ont été détectés chez les contrôles comme chez les patients. Cet étonnant résultat souligne l'existence d'un noyau de microbiote pulmonaire.Dans un deuxième travail, faisant suite aux travaux effectués dans notre laboratoire et qui ont pu mettre en évidence que 19% des pneumopathies nosocomiales étaient déterminées par des microorganismes associés aux amibes (MAAs) de l’eau préalablement ignorés ou négligés, nous avons utilisé un test d'immunofluorescence multiplexe pour tester la prévalence des anticorps contre les MAAs dans le sang de patients admis en réanimation et atteints de pneumopathies et la comparer à la prévalence au moment de l'admission. Comme résultat, nous démontrons que certains MAAs peuvent être plus fréquemment détectés après des épisodes de pneumopathies nosocomiales que lors de l’admission. En outre, la réponse immunitaire aux MAAs semble augmenter lorsque le séjour en réanimation est prolongé. Enfin, nous avons mis au point une stratégie de metagénomique pour tester les prélévements pour lesquels aucune étiologie n’a été retrouvée. [...] / Recently, bacterial microbiota from a limited number of patients with cystic fibrosis and ventilator-associated pneumonia (VAP) was studied using 16S rDNA gene amplification followed by clone libraries construction and sequencing. These studies have showed that the microbial population of patients with respiratory infections was more diverse than expected. In the current study, we use a similar approach to identify exhaustively the pathogens (bacteria, viruses, and fungi) comprising the microbiota associated with episodes of pneumonia developed in the intensive care units (ICU). Our study included patients admitted to ICUswith with episodes of ventilator-associated pneumonia (n = 106), community-acquired pneumonia (n = 32), nosocomial pneumonia without mechanical ventilation (n = 22) and aspiration pneumonia (n = 25). A cohort of 25 patients admitted to ICUs without symptoms of pneumonia were studied as controls. This first part of the work enables to prepare an exhaustive repertoire of nosocomial pneumonia pathogenes; to know the prevalence of the pathogens identified and to identify co-infections frequently observed, and especially to ascertain whether these agents can be identified or not in the respiratory samples of patients without symptoms of pneumonia. To perform this part of work, series of samples, including bronchoalveolar lavage (BAL) samples, blood samples and urine samples were collected. These samples were tested by means of modern molecular tools based on the amplification of conserved genes (bacterial 16S rDNA and fungal 18S rDNA genes), followed by highthroutput cloning and sequencing. The atypical pathogens are targeted by PCR tests using specific primers and probes. We also included culture, amoeba co-culture, serological detection of antibodies against selected agents and urinary antigen testing, to compare these routine tests to molecular approaches. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 were never previously reported in pneumonia samples. Moreover, we found 37 putative new bacterial phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia, 7 viruses and surprisingly 6 plant species. Some pathogens considered being typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species may be detected as commonly in controls as in pneumonia patients which strikingly highlight the existence of a core of pulmonary microbiota.In a second work, following previous works performed in our laboratory which were able to show that 19% of nosocomial pneumonia were determined by micro-organisms associated to amoebae (AAMs) previously ignored or neglected, we used a recent test based on multiplex serology to test for the prevalence of antibodies against the AAMs in the blood of patients admitted to ICU and developed episodes of pneumonia and compare it to the prevalence at the time of admission (controls). As a result, we demonstrate that some AAMs may be more frequently detected after episodes of nosocomial pneumonia than at the admission. In addition, the immune response to AAMS appears to increase when the ICU stay is prolonged.Finally, in order to explore samples for which no microbial aetiology was found, we have developed a subtractive hybridization metagenomic strategy and tested it on different clinical samples. The sensitivity of this strategy was also evaluated. We have demonstrated that our method, based on the detection of DNA and RNA of microorganisms in a single test, allows sensitive detection of different types of microorganisms.