Pseudomonas aeruginosa is an opportunistic pathogen capable of infecting the human cornea. Such infections are difficult to treat, and are often fulminative, in that the infected eye is lost, or severely scarred. The use of alternative therapeutic agents has been necessitated by the frequent failure of conventional antibiotic therapy. Equine hyperimmune antilipopolysaccharide plasma (Anti-LPS) was obtained by the plasmapheresis of suitably immunized horses. The plasma contained 1,O- 1 ,5g/ml of LPS-precipitible IgG antibodies. Topical administration of Anti-LPS as a lavage was shown to be effective against Pseudomonas keratitis in rabbits and guinea pigs. Subsequent use of topical corticosteroids was found to further reduce corneal pathology. The improvement noted in these experimental infections involved all three parameters measured, area of keratitis, depth of lesion, and degree of vascularization. In vitro , Anti-LPS was shown to be rapidly bactericidal for Gram negative bacteria. The plasma can therefore be said to have a dual mechanism of action: antitoxic, and antibacterial. Ocular administration of Anti-LPS, by both the topical and subconjunctival routes, was well tolerated by both rabbits and baboons. In conclusion, Anti-LPS is a potentially useful immunotherapeutic agent with many applications in both veteriary and human medicine, particularly in the treatment of surface infections involving antibiotic-resistant Gram negative bacteria / KMBT_363 / Adobe Acrobat 9.53 Paper Capture Plug-in

Intact bovine Longissimus dovsi muscle was subjected to a mild washing procedure in order to reduce the concentration of the sarcoplasmic fluid. Intact and washed muscle samples were inoculated with Pseudomonas fragi to evaluate the effect of a sarcoplasmic reduction on bacterial growth and subsequent spoilage during storage at 4°C for 12 days. Aseptic controls were stored under similar conditions. Alterations in the water-soluble, salt-soluble, urea-soluble and urea-insoluble protein fractions, as well as the total carbohydrate, pH and bacterial numbers, were monitored in both intact and washed inoculated muscle samples. Scanning and transmission electron microscopy were employed to monitor ultrastructural changes on the muscle surface as a consequence of the growth of P. fragi. Analysis of water-soluble components (non-protein nitrogen, water-soluble proteins and carbohydrates) indicated that the washing procedure effectively removed the majority of these components. Increases in the extractability of the water-soluble and salt-soluble protein fractions were observed in the intact inoculated muscle sample. Alterations in the SDS-gel electrophoretic pattern of the water-soluble, salt-soluble, urea-soluble and urea-insoluble proteins were evident. Total carbohydrate decreased as a result of growth of P. fragi. An increase in pH of the intact muscle occurred as bacterial numbers increased. Significantly (P < 0.01) higher growth rates were observed on the intact muscle tissue than the washed muscle tissue. Relatively little change in the non-protein nitrogen, water-soluble and salt-soluble protein content was observed in the washed inoculated muscle tissue. A slight decrease in total carbohydrate was seen. Minor changes in the SDS-gel electrophoretograms of the salt-soluble proteins were apparent. Little change in pH of the washed inoculated sample occurred due to the growth of P. fragi. Scanning electron micrographs indicated that surface degradation of both intact and washed inoculated muscle samples were apparent only in areas of localized colonization. Glycocalyx appeared to mediate not only cell to cell attachment, but also cell to muscle surface adhesion. Bacteria were observed growing between muscle fibers. Transmission electron micrographs of intact inoculated muscle tissue confirmed the mediation of glycocalyx in bacterial adhesion. Cellular evaginations were present on the surface of the bacteria. Autolysis was minimal in both intact and washed aseptic muscle controls. / Land and Food Systems, Faculty of / Graduate

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 150-153).

Thesis (Ph.D. in Pharmacology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 203-212; 260-261). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (D.P.H.)--University of Michigan.

Thesis (D.P.H.)--University of Michigan.

Pseudomonas aeruginosa is a common and important pathogen in people with cystic fibrosis (CF). Recently epidemic strains of P. aeruginosa associated with increased morbidity, have been identified. The method of transmission is not clear, but there is evidence of a potential airborne route. The aim of this study was to determine whether different strains of P. aeruginosa isolated from people with CF were able to survive within artificially generated aerosols in an aerobiological chamber. Viable P. aeruginosa could still be detected up to 45min after halting generation of the aerosols. All of the strains of P. aeruginosa expressing a non-mucoid phenotype isolated from people with CF had a reduced ability to survive within aerosols compared to an environmental strain. Expression of a mucoid phenotype by the strains of P. aeruginosa isolated from people with CF promoted survival in the aerosol model compared to strains expressing a non-mucoid phenotype.

Made available in DSpace on 2015-07-22T20:50:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-07-27 / P. aeruginosa é um importante microorganismo em infecções de corrente sanguínea. O tratamento da P. aeruginosa resistente aos carbapenêmicos é um desafio, já que as drogas mais utilizadas para este fim, as polimixinas, tem uma ação inferior aos carbapenêmicos. No entanto, o uso combinado de polimixinas com carbapenêmicos tem demonstrado sinergismo em estudos in vitro. Objetivos: Avaliar a resposta ao tratamento com polimixina B versus polimixina B e imipenem em pacientes com infecção da corrente sanguínea associada a assistência à saúde, primária ou secundária, causada por Pseudomonas aeruginosa resistente aos carbapenêmicos e identificar os fatores associados à mortalidade. Métodos: Realizamos um estudo tipo coorte retrospectivo, com pacientes internados no Hospital São Paulo - UNIFESP, no período de 01 de janeiro de 2000 à 31 de dezembro de 2009. A identificação dos pacientes foi realizada através de levantamento de dados da ficha de notificação de hemoculturas com posterior revisão dos prontuários. Os pacientes foram inicialmente divididos em óbitos e sobreviventes e avaliados quanto a exposição a diversos fatores associados à letalidade hospitalar e relacionada a infecção. Foi realizada pesquisa de metalobetalactamase nas amostras de P. aeruginosa que puderam ser recuperadas, por técnica de biologia molecular. Resultados: Foram estudadas 69 infecções de corrente sanguínea por P. aeruginosa resistente aos carbapenêmicos, das quais 35 foram tratadas com monoterapia com polimixina B e 34 com terapia combinada. O óbito relacionado a infecção, definido como aquele que ocorreu nos primeiros 14 dias do diagnóstico da infecção da corrente sanguínea, foi de 42,8% nos pacientes que utilizaram monoterapia e 44,1% naqueles que utilizaram terapia combinada (p=0,917). Foram fatores associados à mortalidade durante a internação hospitalar, o uso prévio de glicopeptídeos (OR 10,71, IC 1,20-95,34, p=0,033) e o escore de Charlson no momento da internação (OR 1,9, IC 1,22-2,94, p=0,004). Foram variáveis associadas à mortalidade relacionada à infecção, a presença de choque séptico (OR 9,99, IC 1,81- 55,22, p=0,006) e uso de nutrição parenteral (OR 7,45, IC 1,23-45,24, p=0,029). Foi encontrada uma alta taxa de mortalidade. A terapia combinada não modificou a evolução dos pacientes. A mortalidade hospitalar no grupo com monoterapia foi de 77,1% entre os pacientes que receberam monoterapia e 79,4% nos que receberam terapia combinada (p=0,819). Em pacientes tratados com terapia combinada, quando analisada a presença ou não de metalobetalactamase, não houve diferença estatisticamente significativa quanto aos desfechos. Conclusões: Nesta população, foram fatores independentes para o óbito durante a internação o uso prévio de glicopeptídeos e a pontuação no score de Charlson e, para o óbito relacionado à infecção, a presença de choque séptico e o uso de nutrição parenteral. A presença de metalo-beta-lactamase não influiu no desfecho. / Pseudomonas aeruginosa is an important pathogen causing nosocomial bloodstream infections. The treatment of carbapenem-resistant P. aeruginosa is a challenge as the drugs used for this purpose, the polymyxins, have lower activity compared with carbapenems. However, it has been suggested that polymyxins have the ability to make gram-negative bacteria more susceptible to other antibiotics. As carbapenems are considered the main drugs against P. aeruginosa, it would be interesting to demonstrate the efficacy of this combination in vivo, targeting a more effective therapy. Objectives: To evaluate the response of the treatment with polymyxin B versus polymyxin B and carbapenem in patients with nosocomial bloodstream infection caused by carbapenenresistant Pseudomonas aeruginosa and identify factors associated with mortality among those patients Methods: A retrospective cohort study was performed at Hospital São Paulo - UNIFESP, from January 1st, 2000 to December 31, 2009. The identification of patients was done through data collection from the blood cultures report. Patients were initially divided into deaths and survivors, and assessed for exposure to various factors potentially associated with in-hospital mortality and infection-related mortality. Presence of metalobetalactamase was tested trough PCR technique. Results: We studied 69 bloodstream infections caused by carbapenems-resistant P. aeruginosa. Thirthy-five were treated with polymyxin B monotherapy and 34 with combined therapy. In- hospital mortality was 77.1% and 79.4% in the monotherapy group and combined therapy group, respectively (p = 0.819). The infection-related mortality was 42.8% among patients who received monotherapy, and 44.1% in those receiving combined therapy (p = 0.917). Factors associated with mortality were previous use of glycopeptides (OR 10.71, CI95% 1.20 to 95.34, p = 0.033) and Charlson score (OR 1.9, CI95% 1, 22 to 2.94, p = 0.004). Infection-related mortality was associated with the presence of septic shock (OR 9.99, CI95% 1.81 to 55.22, p = 0.006) and parenteral nutrition (OR 7.45, CI95% 1.23 - 45.24, p = 0.029). No statistically significant difference was found between patients with MBLharboring and non-MBL-harboring strains treated with combined therapy. Conclusions: No difference was found between the monotherapy and combined therapy group regarding mortality. Independent factors related to in- hospital mortality were prior use of glycopeptides and the Charlson score. Presence of septic shock and use of parenteral nutrition were independently associated with infection-related mortality. / TEDE / BV UNIFESP: Teses e dissertações