Browsing by Subject "Community-Acquired Infections"
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Item Emerging infections: the epidemic of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)(2005-06-09) Race, ElizabethItem The evolving paradigm of pneumonia(2014-06-20) Mortensen, EricItem Optimizing Medical Resources for the Treatment of Infectious Diseases in South Africa(2016-04-04) Davis, Kelly A.; Nwariaku, Fiemu; Raja, Hari; Niwagaba, LillianBACKGROUND: Over the past two decades, healthcare expenditures worldwide have increased dramatically. In an era of rising antibiotic resistance, the need for more effective and efficient utilization of healthcare resources could not be more applicable than in the field of infectious diseases. Based on a review of available literature, several interventions targeted at improving antibiotic stewardship have been successful in decreasing healthcare costs in high income countries. Unfortunately, little research has been done in low income countries, including those on the African continent. South Africa in particular lends itself to further study. Despite spending more of its gross domestic product (GDP) per capita on healthcare than most of its neighbors, South Africa is still faced with many of the healthcare issues present in the rest of the continent, including the rise of multidrug-resistant pathogens and an increased Human Immunodeficiency Virus (HIV) seroprevalence. OBJECTIVE: The objective of this research was to analyze current healthcare practices in the treatment of infectious diseases in South Africa in order to identify areas needing more efficient utilization of resources. METHODS: The objective was accomplished by conducting two prospective observational cohort studies. In the first study, data related to patients presenting to two emergency departments in Cape Town, South Africa, were collected to evaluate the efficacy of clinical decision rules currently used when drawing blood cultures. The decision to collect a set of blood cultures was made by the physician, who then recorded a set of clinical parameters known at the time of collection. In the second study, a quality improvement analysis was done to evaluate effectiveness of current intravenous (IV)-to-oral antibiotic switch therapy practices at a tertiary referral center in Cape Town. During the study, all patients receiving IV antibiotic therapy in the internal medicine wards were followed throughout the course of their IV therapy and were evaluated on their eligibility to switch to oral antibiotic therapy based on a list of criteria. RESULTS: In the first study, 500 blood culture sets were collected from 489 patients. Thirty-nine (7.8%) of these were positive for disease causing pathogens, and 13 (2.6%) contained contaminants. Clinical features that were independently associated with a positive culture result included the presence of diabetes, systolic blood pressure <90 mmHg, diastolic blood pressure <60 mmHg, and a suspected biliary source of infection. Thirty-six (95%) of these positive cultures were found to influence patient management in a significant way. In the second study, 71 (55%) of the 129 patients receiving IV antibiotic therapy met all the criteria for switching to oral antibiotics and only 4 (5.6%) of those were switched once the patient became eligible. Patients eligible for switching were continued on IV therapy for a mean of 3.1 (+/-1.6) days (median=3, Interquartile range (IQR)= 2-4 days) after meeting the criteria, and the most common indications for therapy within this group were community-acquired pneumonia (58.2%), sepsis of unknown cause (13.4%), and urinary tract infection (11.9%). The most common IV antibiotics used in this group were ceftriaxone 1 g (77.6%) and amoxicillin/clavulanate 1.2 g (13.4%). Fifteen (21.1%) of the patients meeting the criteria for switching did not have a blood culture sample taken prior to initiation of therapy. CONCLUSIONS: In the end, the stated objective of the project was met: analyzing current healthcare practices in the treatment of infectious diseases in South Africa helped to identify areas needing more efficient utilization of resources. The first study determined that, while blood cultures are an essential aspect of the treatment of infectious diseases, no consistent set of rules exists that allows physicians to predict when to order these studies. Further, when relying on clinical judgment, the vast majority of blood cultures ordered are negative. The second study identified several key mechanisms that led to inappropriately continued IV antibiotic treatment. The results of both studies highlight the need for more research to facilitate targeted interventions.Item Systems Biology of Staphylococcus Aureus Infection Ex Vivo and in Vitro(2012-07-09) Banchereau, Romain; Ramilo, OctavioStaphylococcus aureus has emerged as one of the most common community-acquired bacterial infections, with significant morbidity and mortality. Emergence of multidrug resistant strains worldwide, combined with limited treatment options demand novel approaches to further elucidate host-pathogen interactions, and especially host responses to infection. To this end, we leveraged systems biology approaches to better characterize the status of the host immune system during S. aureus infection ex vivo and in vitro. The transcriptional profiles of PBMC and whole blood from patients with community-acquired S. aureus infection were characterized by microarray analysis, and leukocyte population frequencies were measured by polychromatic flow cytometry. To refine our understanding of inflammatory networks involved, an in vitro system of antigen-presenting cell stimulation with various pathogens, including S. aureus as well as other bacteria and viruses, and their components, was used to identify early inflammatory programs induced in innate immune cells. To reduce the dimension and complexity of the data generated, we developed modular frameworks to analyze and interpret the fingerprints obtained from both the ex vivo and in vitro studies. // Overall, the blood transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis transcriptional programs, and under-expression of adaptive immunity programs. Flow cytometry and standard cell blood count (CBC) revealed an increase in absolute numbers of circulating monocytes, neutrophils and antigen-presenting cells, including dendritic cells and B cells, combined with a decrease in central memory T cells. To identify transcriptional correlates of clinical heterogeneity, we obtained individual fingerprints and derived the molecular distance to health, a numerical score of transcriptional perturbation for each patient. Patient-by-patient analysis without a priori knowledge of clinical diagnoses identified four major transcriptional clusters based on inflammation, erythropoiesis and interferon-induced profiles. Clinical presentation, bacterial dissemination and time between hospitalization and blood sampling were identified as major factors influencing the signature. The framework obtained from in vitro stimulation of monocyte-derived DC helped us refine the characterization of inflammatory programs activated during S. aureus infection. In addition to inflammatory antibacterial programs, S. aureus induced a subset of interferon response modules, also observed in viral infections and autoimmunity, as well as a specific set of modules linked to cell compartmentalization and lipid biosynthesis. Systems biology approaches provide a global and comprehensive assessment of host responses to acute bacterial infections, bringing a new understanding of disease pathogenesis and underlying patient heterogeneity.