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- Dwyer, R., et al.
(författare)
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Addition of a macrolide to a beta-lactam in bacteremic pneumococcal pneumonia
- 2006
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science Business Media. - 0934-9723 .- 1435-4373. ; 25:8, s. 518-521
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Tidskriftsartikel (refereegranskat)abstract
- In the study presented here, data collected prospectively from 340 adult patients hospitalised in five countries with bacteremic pneumococcal CAP and treated with a beta-lactam +/- a macrolide were analysed retrospectively to evaluate the efficacy of this antimicrobial combination. Univariate and multivariate analyses revealed no significant effect on case fatality rate when a macrolide/beta-lactam regimen was used as initial therapy. Results were not affected by severity of illness, or by excluding patients who died within 2 days of admission. Identified predictors of death in a multivariate regression model were age greater than 65 years (OR=2.6), two or more lung lobes affected (OR=2.2), and severity of disease as estimated using the acute physiology score (APS)greater than 8.
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| 4. |
- Giefing, C, et al.
(författare)
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Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies
- 2008
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205:1, s. 117-131
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Tidskriftsartikel (refereegranskat)abstract
- Pneumococcus is one of the most important human pathogens that causes life-threatening invasive diseases, especially at the extremities of age. Capsular polysaccharides (CPSs) are known to induce protective antibodies; however, it is not feasible to develop CPS-based vaccines that cover all of the 90 disease-causing serotypes. We applied a genomic approach and described the antibody repertoire for pneumococcal proteins using display libraries expressing 15–150 amino acid fragments of the pathogen's proteome. Serum antibodies of exposed, but not infected, individuals and convalescing patients identified the ANTIGENome of pneumococcus consisting of ∼140 antigens, many of them surface exposed. Based on several in vitro assays, 18 novel candidates were preselected for animal studies, and 4 of them showed significant protection against lethal sepsis. Two lead vaccine candidates, protein required for cell wall separation of group B streptococcus (PcsB) and serine/threonine protein kinase (StkP), were found to be exceptionally conserved among clinical isolates (>99.5% identity) and cross-protective against four different serotypes in lethal sepsis and pneumonia models, and have important nonredundant functions in bacterial multiplication based on gene deletion studies. We describe for the first time opsonophagocytic killing activity for pneumococcal protein antigens. A vaccine containing PcsB and StkP is intended for the prevention of infections caused by all serotypes of pneumococcus in the elderly and in children.
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- Landgren, O, et al.
(författare)
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A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin's lymphoma
- 2004
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 255:6, s. 664-673
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Tidskriftsartikel (refereegranskat)abstract
- Background. Splenectomy is accompanied by a life-long risk of overwhelming postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS) encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive prophylactic efforts the mortality and morbidity rates remain high. The present study was based on a strategy with a predefined vaccination algorithm including repeated 23-valent pneumococcal vaccinations and monitoring of pneumococcal antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL) patients were compared with those patients splenectomized due to immune-mediated cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)] and also individuals who were splenectomized because of trauma (TRAUMA). Methods. A total of 311 splenectomized individuals were included in this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their individual anti-PS antibody levels measured by enzyme-linked immunosorbent assay technique the patients were revaccinated with 23-valent pneumococcal PS vaccine up to four times in accordance with the predefined algorithm. For each vaccination occasion, serum was collected at vaccination, after 1 month +/- 2 weeks (peak), and after 1 year +/- 6 months (follow-up). Patient files, a national population-based database, and microbiological databases were checked for 124 HL patients to identify OPSI. Results. A significant response was recorded on primary vaccination as well as on two revaccination occasions for HL, AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time elapsed between splenectomy and first pneumococcal vaccination was found to be associated with mean PS antibody levels at prevaccination, peak or follow-up. No severe adverse events were reported. Amongst 124 clinically monitored HL patients, 10 OPSI were recorded in seven patients during the study period. One of these patients, a middle-aged female, died as a result of fulminant pneumococcal bacteraemia, which was her third OPSI during a 7-year period. Conclusions. A significant response to pneumococcal PS vaccination was found in all three groups (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary and repeated vaccinations were safe. Until further knowledge is gained regarding the protective concentration of serotype-specific antibody concentrations we believe that the value of vaccination and frequent revaccination (every 1-5 years) in combination with education of patients and health care professionals and clinical monitoring is beneficial for these patients at risk for OPSI.
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