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Dissertation (Ph.D.)--University of South Florida, 2006. / Title from PDF of title page. Document formatted into pages; contains 90 pages. Includes vita. Includes bibliographical references.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen associated with significant morbidity and mortality. Previous colonisation with this pathogen is a risk factor for the development of subsequent infection. Tolllike receptors (TLRs) are a family of transmembrane receptors of the innate immune system that recognize pathogen-associated molecular patterns. The role of nasal colonisation of S. aureus has started to receive more attention. In spite of this, there are not enough studies looking at its effects on human primary nasal epithelial cells and their response to TLR ligands. The respiratory tract itself seems to pose a contradiction given by the clinical observation that its upper portion (nasal compartment) allows the growth of bacteria, acting like a reservoir, whereas the lower portion (lung compartment) reacts with an exuberant inflammatory response to the same organisms, as noted during pneumonia. The mechanism related with this phenomenon remains to be elucidated. A negative regulator of the TLR signalling cascade called toll-interacting protein (tollip) has been demonstrated to induce hyporesponsiveness in the gastrointestinal tract in the presence of bacteria. So far, tollip has not been demonstrated in the respiratory tract. Aims: To compare the responses of the upper and lower respiratory tract to TLR ligands, to characterise the role of tollip in the respiratory tract and its effects in the induction of tolerance, and to determine the cellular response to nasal carriage of S. aureus. Materials and Methods: The cell line RPMI 2650 (representative of nasal epithelium) and the cell line A549 (representative of type II alveolar epithelium) were used to establish the cytokine response to stimulation with TLR ligands and to demonstrate the presence of tollip protein by immunocytochemistry and enzymelinked immunosorbent assay (ELISA). Primary human nasal epithelial and type II alveolar epithelial cells were isolated and cultured from consented subjects. The cytokine response to stimulation was measured using cytokine bead array and the presence of tollip was determined by immunofluorescence and quantitative polymerase chain reaction. The presence of TLRs was assessed by immunocytochemistry in primary nasal and type II alveolar epithelial cells and the response to stimulation with the TLR9 agonist CpG-C ODN was assessed in these cells as well as in primary human type II alveolar epithelial cells. Subjects were also assessed for nasal carriage of S. aureus and their associated cytokine responses. Results: The RPMI 2650 cell line, despite retaining phenotypic characteristics of the nasal epithelium, appears unresponsive to stimulation with TLR ligands. In contrast, the A549 cell line responded significantly to stimulation with TLR ligands. Primary human nasal epithelial cells responded by secreting higher amounts of interleukin (IL)-8 and IL-6 in response to stimulation with S. aureus peptidoglycan (PGN) and tumour necrosis factor alpha (TNF-α) with a strong trend toward statistical significance. These cells did not respond to stimulation with Pseudomonas aeruginosa LPS. Primary type II alveolar epithelial cells responded significantly to stimulation with S. aureus PGN by increasing the secretion of IL-8, IL-6, IL-1β, TNF-α and IL-10 into cultured supernatant. Cells from the upper respiratory tract displayed a more tolerant phenotype given by the lower levels in cytokine production in response to stimulation with S. aureus PGN, in contrast to alveolar epithelial cells. TLRs were identified in primary nasal epithelial cells. The negative regulator tollip was identified in cell lines as well as primary cells of the respiratory tract in its three segments: nasal, bronchial and type II alveolar. It was not possible to demonstrate an up-regulation of tollip after stimulation with TLR ligands in any of the cell types studied, although, it was possible to observe a significantly higher constitutive level in tollip mRNA transcripts from primary nasal epithelial cells in comparison to type II alveolar epithelial cells. TLR9 was identified in human primary nasal epithelial cells, although it was not possible to observe an increase in cytokine production after stimulation with a TLR9 agonist. TLR9 was expressed strongly in primary type II alveolar epithelial cells which responded by significantly increasing IL-8 production after stimulation with CpG-C ODN. Primary nasal epithelial cells from individuals who carry S. aureus exhibit a proinflammatory profile, as evidenced by higher basal levels of IL-8 and IL-6 in comparison to non-colonised controls. Conclusion: The upper respiratory tract epithelium displays a tolerant phenotype in response to stimulation with TLR ligands in comparison to the lower respiratory epithelium, potentially favouring nasal colonisation by S. aureus. Tollip m-RNA transcripts appear to be up-regulated constitutively in the nasal epithelium which might favour this response. Staphylococcus aureus colonisation is however associated with a local pro-inflammatory state in the nasal epithelium of carrier individuals.

Thesis (Ph. D.)--Virginia Commonwealth University, 2009. / Prepared for: School. of Pharmacy. Title from title-page of electronic thesis. Bibliography: leaves 129-140.

Class of 2006 Abstract / 1College of Pharmacy, University of Arizona 2El Rio Special Immunology Associates Objectives: To compare antibiotic resistance patterns of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in HIV patients and the general population. We hypothesized that CA- MRSA strains in HIV patients may show a decreased susceptibility to trimethoprim/sulfamethoxazole (TMP/SMX) because of its widespread use for prophylaxis of Pneumocystis carinii pneumonia (PCP) in this population. Methods: Susceptibility reports for all Staphylococcus aureus isolates collected between November 1, 2004 and November 1, 2005 from Special Immunology Associates (SIA), an HIV clinic, and the neighboring Carondelet St. Mary’s Hospital Emergency Center (SMH) were analyzed. Results: Twenty-five cases in HIV patients at SIA (Mean age 40, Race: 21 Caucasian, 4 Hispanic) and 102 cases at SMH (Mean age 37, Race: 45 Caucasian, 34 Hispanic, 12 Native American, 8 African American) were identified as CA-MRSA. More than 95% of patients presented with skin infections and a seasonal peak was identified between June and October. No cases of TMP/SMX resistance were found at either institution despite the fact that 40% of the SIA patients with CA-MRSA had been exposed to TMP/SMX for PCP prophylaxis in the past. Susceptibility varied between SIA and SMH, with significant differences in susceptibility to tetracycline (57% vs. 86%, p<0.001) and levofloxacin (38% vs. 60%, p < 0.001). Erythromycin resistance in both institutions was greater than 90%. Conclusions: All CA-MRSA isolates from an HIV clinic and a neighboring health care facility were susceptible to TMP/SMX. HIV patients with CA-MRSA did not show a decrease in susceptibility to TMP/SMX, despite its routine use for prophylaxis in this population.

Nonmenstrual toxic shock syndrome (TSS) due to Staphylococcus aureus can lead to significant morbidity and mortality. While drotrecogin alfa (DA) has been employed in patients with Methicillin-resistant Staphylococcus aureus (MRSA) severe sepsis and septic shock, its utility in TSS remains unclear. The authors report a case of severe sepsis in the setting of MRSA-associated TSS that responded to treatment with DA. This case illustrates a potential role for DA in the treatment of toxic shock syndromes and emphasizes the importance of aggressive diagnostic and therapeutic modalities in approaching these conditions.

Vancomycin has been considered first-line treatment for bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) despite treatment failures in up to 20% of patients with MRSA bacteremia secondary to endocarditis. However, trimethoprim-sulfamethoxazole (TMP-SMX) is as effective as vancomycin for the management of MRSA bacteremia. secondary to endocarditis in injection drug users. We report the successful management of a left ventricular assist device-related MRSA infection with persistent MRSA bacteremia that failed to respond to vancomycin, linezolid, and quinupristin/dalfopristin but did respond to TMP-SMX.

Staphylococcus aureus is a common bacterium found on the skin and mucosal membranes of about 20% of the population. S. aureus growth on the skin is harmless, but if it bypasses the skin it can causes life-threatening diseases such as pneumonia, meningitis, bacteremia, and sepsis. Antibiotic-resistant strains of S. aureus, called Methicillin Resistant S. aureus (MRSA), are resistant to most antibiotics except vancomycin. However, vancomycin resistant strains of MRSA are becoming more common. In this study, 12 phages were isolated capable of infecting human S. aureus and/or MRSA strains. Five phages were discovered through mitomycin C induction of prophages and seven phages were found through enrichment of environmental samples. Primary S. aureus strains were also isolated from environmental sources to be used as tools for phage discovery and isolation as well as to examine the target cell host range of the phage isolates. S. aureus isolates were tested for susceptibility to oxacillin in order to determine methicillin-resistance. Experiments were performed to assess the host range and killing potential of newly discovered phage. The M1M4 phage had the broadest host range and lysed 12% of the S. aureus strains that were tested. The host ranges were reinforced by spectrophotometric assay data which showed a reduction in bacterial optical density of 1.3 OD600. The phages were used to decontaminate MRSA from fomites (glass and cloth) and successfully reduced colony forming units by 1-2 logs, including tests of a phage cocktail against a cocktail of MRSA isolates. Our findings suggest that phage treatment can be used as an effective tool to decontaminate human MRSA from both hard surfaces and fabrics.

Meticillinresistent staphylococcus aureus (MRSA) är en bakterie som är resistent mot ett flertal antibiotika. Det är en bakterie som har ökat både i Sverige och i resten av världen. Tidigare var smittspridningen av MRSA vanligt förekommande på sjukhusen men har på senare tid även blivit allt mer förekommande utanför sjukvården. Att smittas av MRSA kan innebära svåra infektionssjukdomar som pneumoni, urinvägsinfektion och sepsis. För att minimera smittspridningen av MRSA flyttas patienter till isoleringssalar, vilket kan resulterat i lidande för patienten. Syfte är att belysa MRSA smittade patienters upplevelse av möten med hälso- och sjukvårdspersonal. Denna litteraturöversikt är baserad på tio vetenskapligt granskade artiklar, nio av artiklarna är kvalitativa och en är kvantitativ. De vetenskapliga artiklarna har noggrant granskats och därifrån har en sammanställning med teman till resultatet bildats. Databaserna CINAHL Complete, PubMed och Academic Search Complete har använts. Utifrån de tio artiklarna sammanställdes fyra teman som belyser patienters upplevelser. Dessa redovisas under i följande rubriker: Hälso- och sjukvård samt närståendes bemötande av patienter med MRSA, Psykologiskt trauma, Negativa och positiva upplevelser av isolering samt Kunskap om MRSA. Katie Erikssons teori med fokus på lidande diskuteras tillsammans med resultatet, utifrån patientens perspektiv. En av sjuksköterskornas centrala roll inom omvårdnadsarbetet är förebyggandet av smittspridning av MRSA, främst genom basala handhygienrutiner. Resultatet påvisade faktorer som kan påverka patienters syn på vården gällande MRSA. Där många patienter upplever att hälso- och sjukvårdspersonalen saknar kunskap angående smittspridning, infektioner och isoleringsrestriktioner. / Meticillin-resistant staphylococcus aureus (MRSA) is a bacteria that is resistant to a variety of antibiotics. This bacteria has increased both in Sweden and worldwide. Previously, the spread of MRSA was common in hospitals, but has recently become more common outside the healthcare sector. To be infected with MRSA often involves severe infectious such as pneumonia, urinary tract infection and sepsis. To minimize the spread of MRSA, patients are moved to isolation, which can result in suffering. To shed light on the experiences of MRSA-infected patients’ interactions with healthcare professionals. This literature review is based on ten scientifically reviewed articles, nine are qualitative and one is quantitative. The scientific articles have been carefully reviewed and from there have a summary with the themes to the result, been formed. Databases CINAHL Complete, PubMed and Academic Search Complete have been used. Based on the ten articles, four themes summarized the patient's experiences. These are listed under the following headings: Healthcare, and relatives response to patients with MRSA, Psychological trauma, Negative and positive experiences of insulation, and Knowledge of patients and healthcare professionals. Katie Eriksson's theory on suffering is discussed with the result, based on patient's perspective. One of the nurses' central role in nursing work is preventing contagious spread of MRSA, primarily through basic hand hygiene routines. Our results indicate that there are factors that may affect patients' views on the care of MRSA. Where many patients experience that healthcare professionals lack knowledge about spread of infection, infections and isolation restrictions.

Bakgrund: Methicillin-resistent Staphylococcus aureus (MRSA) är en variant av gula stafylokocker som är resistenta mot meticillin vilket resulterar i att MRSA är svår behandlat. MRSA är infektioner som finns på bland annat huden och i slemhinnor, bakterien kan orsaka svåra livshotande infektioner. Vilket resulterar i ett stort lidande för patienten och höga samhällskostnader. Syfte: Syftet var att beskriva faktorer i sjuksköterskans omvårdnadsarbete som kan påverka smittspridningen av Methicillin-resistent Staphylococcus aureus (MRSA). Metod: Denna litteraturöversikt utgår från åtta kvalitativa och kvantitativa vetenskapliga artiklar som systematiskt söktes fram i databaserna PubMed och Cinahl Complete. Artiklarnas resultat tematiserades enligt Fribergs analysmodell. Resultat: Resultatet visade att sjuksköterskor behöver få mer kunskap genom upprepade utbildningar av MRSA och smittspridning samt ha en god handhygien för att påverka smittspridning. De hygienrutiner och riktlinjer som finns angående MRSA och smittspridning behöver utvecklas och förtydligas.  Sammanfattning: Sjuksköterskor behöver ta ansvar för sin yrkesmässiga utveckling genom att initiera utbildning för att kunna bidra till en säker vård. Sjuksköterskor behöver ta ansvar för att ständigt utvecklas och söka nya kunskaper. Kunskap och utbildning bidrar till evidensbaserad vård vilket kan förhindra smittspridning av MRSA. / Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a variant of staphylococcus aureus that is resistant to methicillin, which results in MRSA being difficult to treat. MRSA infections can be found on the skin and in mucous membranes of afflicted patients. Which results in great suffering for the patient and high societal costs. Aim: The aim of this study was to describe how nurse’s nursing care can affect spread of infection of Methicillin-resistant Staphylococcus aureus (MRSA). Method: This literature review is based on eight qualitative and quantitative scientific articles that were systematically searched in the databases PubMed and Cinahl Complete. The results of the articles were themed according to Friberg's analysis model. Results: The results showed that nurses need to gain more knowledge through repeated training on MRSA and the spread of infection and have good hand hygiene to affect spread of infection. The hygiene routines and guidelines that exist regarding MRSA and the spread of infection need to be developed and clarified. Summary: Nurses need to take responsibility for their professional development by initiating training in order to contribute to safe care. Nurses need to take responsibility for constantly developing and seeking new knowledge. Knowledge and education contribute to evidence-based care, which can prevent the spread of MRSA.