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Infective Endocarditis: aspects of pathophysiology, epidemiology, management and prognosis
Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Infective endocarditis (IE) is a rare but complex disease that is fatal if untreated. With a modern combination of antimicrobial therapy and heart valve surgery, mortality is still 10-20 %. The structure of the endocarditis vegetation impedes the penetration of phagocytic cells such as monocytes and granulocytes. This leads to high bacterial counts inside the vegetation and the need for long treatment courses with a combination of intravenously administered bactericidal antibiotics.

The aim of this thesis was to study the changes in epidemiology, management, and mortality at our hospital between 1980 and 2001, and to identify prognostic factors associated with mortality. To assess the issue of referral bias, differences between referred episodes and episodes from our local community were studied. Additional aims were to study the occurrence of the pro-chemotactic cytokines IL-8 and TNF-α in heart valves and vegetations during the active phase of IE, and to study the effect of the glycopeptide antibiotic vancomycin in dense staphylococcal cultures in vitro. As it is a rare and complex disease, management of IE is usually complicated for non-specialists. For this reason a computerised decision support system for IE was developed and evaluated.

Between 1980 and 2001, the occurrence of Staphylococcus aureus IE and the use of early heart valve surgery increased significantly, regardless of whether the episodes were referred or of local origin. Glycopeptide antibiotics, mainly vancomycin, were used more frequently, especially among referred patients. Referred patients were younger, predominantly male, had more complications, and received surgical treatment more often than patients from our local community. The reason for the lower frequency of female patients in the referral cohort cannot be explained by more comorbidity or fewer complications. The differences between referred and local episodes seen in our study highlight the need for assessment and adjustment for referral bias in IE studies (Paper I).

In six patients who needed early heart valve surgery, the largest numbers of IL-8-containing cells, and the greatest amount of inflammation, were seen in patients with short preoperative antimicrobial treatment courses. No such relationships were seen with respect to TNF-α-containing cells. The IL-8-containing cells and the inflammatory cells were predominantly scattered in the heart valve stroma or in the margin of the vegetation (Paper II). The primary effect of IL-8 is to stimulate chemotaxis of polymorphonuclear neutrophil granulocytes. This indicates that there is no deficiency of IL-8 in the area close to the vegetation as a cause of the localised agranulocytosis often present inside the vegetation.

Our study revealed a need for computerised decision support systems (DSSs) in the field of IE, but to be used in clinical practice these DSSs need be part of knowledge bases covering larger domains (Paper IV). Some of our initial ideas described in Paper III, especially the use of Internet technology and the combination of rule-based advice and explanatory hypertext, will probably be included in these knowledge bases.

In vitro, there is a rapid reduction of free vancomycin in broth containing dense staphylococcal cultures. Consequently, there is a simultaneous increase in broth MICs, particularly in high inocula, which is not caused by a development of resistance (Paper V). These findings need further evaluation in vivo, but indicate that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis.

Diabetes mellitus and moderate to severe heart failure were independent risk factors for 6-month mortality in left-sided, Duke definite IE episodes, regardless of referral or local origin of the episodes. Early heart valve surgery had a positive impact on the 6-month mortality in the referral cohort of episodes, which may be due to referral bias (Paper VI).

Place, publisher, year, edition, pages
Linköping University Electronic Press, 2008. , 42 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1017
Keyword [en]
epidemiology, Infective endocarditis (IE), heart valve surgery, monocytes, granulocytes, staphylococ
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:liu:diva-12274ISBN: 978-91-85895-83-0 (print)OAI: oai:DiVA.org:liu-12274DiVA: diva2:18510
Public defence
2008-05-14, Elsa Brändströmsalen, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2015-11-19
List of papers
1. Changes in left-sided infective endocarditis over two decades at a Swedish university hospital: and evaluation of the importance of referral bias
Open this publication in new window or tab >>Changes in left-sided infective endocarditis over two decades at a Swedish university hospital: and evaluation of the importance of referral bias
Manuscript (Other academic)
Identifiers
urn:nbn:se:liu:diva-13331 (URN)
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2010-01-13
2. IL-8 and tumor necrosis factor alpha in heart valves from patients with infective endocarditis
Open this publication in new window or tab >>IL-8 and tumor necrosis factor alpha in heart valves from patients with infective endocarditis
Show others...
2002 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 34, no 10, 759-762 p.Article in journal (Refereed) Published
Abstract [en]

The embedding of bacteria in the vegetation of infective endocarditis impedes the penetration of phagocytic cells. IL-8 has a stimulating effect on the immune system, particularly with respect to chemotaxis and activation of granulocytes. Tumor necrosis factor alpha (TNF-) is 1 of the major proinflammatory cytokines. IL-8 and TNF- were visualized by means of immunohistochemistry in paraffin-embedded heart valve biopsies from 6 patients with infective endocarditis who required cardiac surgery during the active phase of the infection. In 5/6 patients there were signs of inflammation, and in these patients IL-8- and TNF- -containing cells were visualized in the heart valve stromas or vegetations. The largest numbers of IL-8-containing cells, and the greatest amount of inflammation, were seen in patients with short preoperative treatment courses. No such relationships were seen with respect to TNF- -containing cells. These observations may suggest that the occurrence of IL-8-containing cells in infected heart valves could be used as a marker of disease activity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13332 (URN)10.1080/00365540210147912 (DOI)
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2009-08-17
3. Extended telemedical consultation using Arden Syntax based decision support, hypertext and WWW technique
Open this publication in new window or tab >>Extended telemedical consultation using Arden Syntax based decision support, hypertext and WWW technique
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1997 (English)In: Methods of Information in Medicine, ISSN 0026-1270, Vol. 36, no 2, 108-114 p.Article in journal (Refereed) Published
Abstract [en]

There is an obvious need for geographic distribution of expert knowledge among several health care units without increasing the cost of on-site expertise in locations where health care is provided. This paper describes the design of a knowledge-based decision-support system for extended consultation in clinical medicine. The system is based on Arden Syntax for Medical Logic Modules and hypertext using World Wide Web technology. It provides advice and explanations regarding the given advice. The explanations are presented in a hypertext format allowing the user to browse related information and to verify the relevance of the given advice. The system is intended to be used in a closed local network. With special precautions regarding issues of safety and patient security, the system can be used over wider areas such as in rural medicine. A prototype has been developed in the field of clinical microbiology and infectious diseases regarding infective endocarditis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13333 (URN)9242006 (PubMedID)
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2013-02-19
4. A study of the usage of a decision-support system for infective endocarditis
Open this publication in new window or tab >>A study of the usage of a decision-support system for infective endocarditis
2000 (English)In: Medical informatics and the Internet in medicine (Print), ISSN 1463-9238, E-ISSN 1464-5238, Vol. 25, no 1, 1-18 p.Article in journal (Refereed) Published
Abstract [en]

The objective of this study was to examine a design for a World Wide Web-based decision-support system in use by clinically active physicians. A prototype implementation of the design concerned management of infective endocarditis patient cases. The design was based on an integration of hypertext and rule-based knowledge. In the study sessions, physicians in the field of internal medicine worked on managing authentic patient cases in a laboratory setting. Data was collected from interviews with the physicians using video recordings and stimulated recall technique. The qualitative data was analysed according to the constant comparative method in order to develop a model of the physicians' usage of the system. The resulting model describes perceived contributions and criteria for usefulness of the system. The ways the physicians used the system showed that it was able to provide patient-specific support for confirming clinical decisions, for higher-level patient management, and for preparing for and initiating expert consultations. Users also stated that new medical knowledge could be gained as a side effect of using the system.

Keyword
Decision-support System, Endocarditis, Qualitative Methodology, Evaluation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13334 (URN)10.1080/146392300298229 (DOI)
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2013-02-19
5. Rapid decrease of free vancomycin in dense staphylococcal cultures
Open this publication in new window or tab >>Rapid decrease of free vancomycin in dense staphylococcal cultures
Show others...
2005 (English)In: European journal of clinical microbiology and infectious diseases, ISSN 0934-9723, Vol. 24, no 9, 596-602 p.Article in journal (Refereed) Published
Abstract [en]

Bacterial numbers in broth cultures were determined by bioluminescence assay of intracellular bacterial ATP. Broth MICs for strains of Staphylococcus epidermidis (ATCC 14990 and 35984) and Staphylococcus aureus (ATCC 25923, 29213 and 6538) were determined for cultures with different inocula (105–108 bacteria/ml) after 24 h of incubation in supplemented Mueller–Hinton broth containing vancomycin. All of the tested strains except one were susceptible to methicillin, and all of the strains were susceptible to vancomycin. Free vancomycin concentrations in the broth cultures of all strains were determined with an agar well bioassay after 24 h of incubation. Free vancomycin concentrations and bacterial numbers of ATCC 35984 and ATCC 29213 were also determined after 0.5, 2, 4, and 8 h. In a low inoculum (105 bacteria/ml), the broth MICs were 1–4 μg/ml. In a high inoculum (∼108 bacteria/ml), the broth MICs increased two- to fourfold to 4–8 μg/ml. In dense inocula (∼109–1010 bacteria/ml), the concentrations of free vancomycin in the broth were reduced, in most cases below the detection limit of the bioassay (≤0.5 μg/ml). This reduction of free vancomycin was fast, occurring in initially dense inocula in less than 30 min. No emergence of resistance was seen. These results show a rapid reduction of free vancomycin in the broth and a simultaneous increase in broth MICs in high inocula, without development of resistance. This indicates that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13335 (URN)10.1007/s10096-005-0011-0 (DOI)
Available from: 2008-06-18 Created: 2008-06-18
6. Prognostic factors for 6-month mortality in infective endocarditis: a retrospective study in a Swedish referral hospital
Open this publication in new window or tab >>Prognostic factors for 6-month mortality in infective endocarditis: a retrospective study in a Swedish referral hospital
Manuscript (Other academic)
Identifiers
urn:nbn:se:liu:diva-13336 (URN)
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2010-01-13

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