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Rapid decrease of free vancomycin in dense staphylococcal cultures
Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
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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.

Place, publisher, year, edition, pages
2005. Vol. 24, no 9, 596-602 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-13335DOI: 10.1007/s10096-005-0011-0OAI: oai:DiVA.org:liu-13335DiVA: diva2:18508
Available from: 2008-06-18 Created: 2008-06-18
In thesis
1. Infective Endocarditis: aspects of pathophysiology, epidemiology, management and prognosis
Open this publication in new window or tab >>Infective Endocarditis: aspects of pathophysiology, epidemiology, management and prognosis
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
epidemiology, Infective endocarditis (IE), heart valve surgery, monocytes, granulocytes, staphylococ
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-12274 (URN)978-91-85895-83-0 (ISBN)
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

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Ekdahl, ChristerHanberger, HåkanHällgren, AnitaNilsson, MariaNilsson, Lennart E.

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