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Biomedical subjects

B J Kullberg

Publications and source records attributed to B J Kullberg.

At least 19 recordsLinked to original sources
PubMed2007

Complicating infectious foci in patients with Staphylococcus aureus or Streptococcus species bacteraemia.

Complicating infectious foci resulting from haematogenous or local spread of microorganisms are observed frequently in patients with Staphylococcus aureus bacteraemia (SAB) or Streptococcus species bacteraemia (SSB). The aim of this study was to compare the epidemiology of complicating infectious foci during SAB and SSB in a university hospital in The Netherlands. The charts of all adult patients diagnosed with SAB or SSB (except for Streptococcus pneumoniae bacteraemia) from July 2002 until December 2004 were reviewed retrospectively. Overall, 180 immunocompetent patients were identified, 127 with SAB and 53 with SSB. The percentage of patients with complicating infectious foci (39% of SAB patients, 25% of SSB patients) did not differ significantly between the groups. Endocarditis and cerebral involvement, however, were significantly more common in the SSB group. Of all complicating infectious foci, 32% lacked guiding signs or symptoms and 10% were detected only at autopsy. Factors associated with the development of complicating infectious foci were a delay in treatment for more than 48 h after the onset of symptoms, community acquisition, persistently positive blood cultures, congenital heart disease, and the presence of foreign bodies or prosthetic valves. Infection-related mortality was 18% in SAB patients and 11% in SSB patients and was significantly higher in patients with complicating infectious foci (29 vs. 9%). In conclusion, complicating infectious foci develop in approximately one-third of all patients with SAB and SSB. An active approach that entails searching for the complicating infectious foci is warranted in these patients, because only two-thirds of complicated infectious foci have guiding symptoms or signs, and infection-related mortality is significantly increased in patients with complicating infectious foci compared to patients without these infections.

Bacteremia↗
PubMed2006

[Optimalisation of the antibiotic policy in The Netherlands. XI. The national electronic antibiotic guide'SWAB-ID' for use in hospitals].

The 'Stichting Werkgroep Antibioticabeleid' (Dutch Working Party on Antibiotic Policy) has developed an electronic national antibiotic guide for the antibiotic treatment and prophylaxis of common infectious diseases in hospitals. This guide also contains information on the most important characteristics of antimicrobial drugs. Advice on antibiotic treatment is based on existing national evidence-based guidelines, where available. Where no guideline is available, the advice is based on an inventory of the antibiotic policies of the 12 Dutch centres with an infectious disease or medical microbiology training programme. The national antibiotic guide can be accessed through the SWAB website (www.swab.nl) and can also be downloaded on PDA/PocketPC, free of charge. Every hospital antibiotic formulary committee in the Netherlands will be offered the opportunity to edit The national version for local use.

Anti-Bacterial Agents↗
PubMed2006

Recognition of pathogenic microorganisms by Toll-like receptors.

Toll-like receptors (TLRs) have been identified as a major class of pattern-recognition receptors. Recognition of pathogen-associated molecular patterns (PAMPs) by TLRs, either alone or in heterodimerization with other TLR or non-TLR receptors, induces signals responsible for the activation of innate immune response. Recent studies have demonstrated a crucial involvement of TLRs in the recognition of all the major classes of microbial pathogens. By studying fungal infection in knock-out mice deficient in either TLRs or TLR-associated adaptor molecules, it appeared that specific TLRs play differential roles in the activation of the various arms of the innate immune response. Recent data also suggest that TLRs offer escape mechanisms to certain pathogenic microorganisms, especially through TLR2-driven induction of antiinflammatory cytokines. These new data have substantially increased our knowledge of the recognition of microbial pathogens, and this remains one of the most active areas of research in the field of infectious diseases.

Animals↗
PubMed2006

FDG-PET for imaging of non-osseous infection and inflammation.

UNLABELLED: FDG-PET is emerging as a promising imaging technique in non-osseous infectious and inflammatory diseases, as an increasing number of reports are appearing in literature. In general, sensitivity of FDG-PET in diagnosing non-osseous infections compares favorably to other diagnostic modalities. Lower specificity due to FDG accumulation in conditions involving leukocyte activation and malignancy may be overcome by implementing FDG-PET in a diagnostic protocol. In fever of unknown origin, FDG-PET appears to be of great advantage as malignancy, inflammation and infection can be detected. Studies on standardized uptake value ratios, uptake patterns and dynamics may be helpful to increase specificity. Image fusion combining PET and CT facilitates anatomical localization of increased FDG-uptake and better guiding for further diagnostic tests to achieve a final diagnosis. More data on the utility of FDG-PET to monitor the response to treatment will be available in near future. Early reports on FDG-PET during treatment follow-up in large vessel vasculitis already showed promising RESULTS: In conclusion, the body of evidence on the utility of FDG-PET in non-osseous infection and inflammation is growing and FDG-PET may become one of the preferred diagnostic procedures for these diseases.

Clinical Trials as Topic↗
PubMed2005

[Optimizing the antibiotics policy in The Netherlands. VIII. Revised SWAB guidelines for antimicrobial therapy in adults with community-acquired pneumonia].

The Dutch Working Party on Antibiotic Policy (SWAB) has revised the 1998 guideline for community-acquired pneumonia (CAP) in light of changing resistance patterns for common pathogens and new developments in epidemiology, diagnostic testing and treatment strategies. The current guideline is applicable to both primary and inpatient care, and has been developed by delegates of all professional organisations involved in the treatment of CAP, following recommendations for evidence-based guideline development. Assessment of a patient's 'severity of illness' at presentation is considered important when choosing an optimal empirical antibiotic regimen for CAP. Severely-ill patients should be treated with antibiotics covering the most important expected pathogens, including Legionella. Assessment of the severity of illness may be facilitated by the use of validated scoring systems like the pneumonia severity index and the 'confusion, urea, respiratory-rate, blood-pressure, 65-years-of-age' (CURB-65) score. Patients can also be stratified based on their location during treatment: in the community, a normal ward or an intensive-care unit. Legionella urine antigen testing is considered an important tool in the process of deciding on an optimal antibiotic regimen for CAP. Empirical therapy should be replaced with pathogen-directed therapy if the causative agent is identified.

Age Factors↗
PubMed2005

Quality of antibiotic use for lower respiratory tract infections at hospitals: (how) can we measure it?

BACKGROUND: To assess and improve the quality of antibiotic use in patients with community-acquired pneumonia (CAP) and acute exacerbation of chronic bronchitis or chronic obstructive pulmonary disease (AECB), a valid set of quality indicators is required. This set should also be applicable in practice. METHODS: Guidelines and literature were reviewed to derive potential indicators for quality of antibiotic use in treating hospitalized patients with lower respiratory tract infection (LRTI). To assess the evidence base of each indicator, a literature review was performed. Grade A recommendations were considered valid. For grade B-D recommendations, an expert panel performed a consensus procedure on the indicator's relevance to patient health, reduction of antimicrobial resistance, and cost containment. To test applicability in practice, feasibility, opportunity for improvement, reliability, and case-mix stability were determined for a data set of 899 hospitalized patients with LRTI. RESULTS: None of the potential indicators from guidelines and literature were supported by grade A evidence. Nineteen indicators were selected by consensus procedure (12 indicators for CAP and 7 indicators for AECB). Lack of feasibility and of opportunity for improvement led to the exclusion of 4 indicators. A final set of 15 indicators was defined (9 indicators for CAP and 6 indicators for AECB). CONCLUSIONS: A valid set of quality indicators for antibiotic use in hospitalized patients with LRTI was developed by combining evidence and expert opinion in a carefully planned procedure. Subjecting indicators to an applicability test is essential before using them in quality-improvement projects. In our demonstration setting, 4 of the 19 indicators were inapplicable in practice.

Anti-Bacterial Agents↗
PubMed2005

[Improved diagnostics in invasive aspergillosis and systematic monitoring in patients at high risk of infection].

Invasive aspergillosis remains an important cause of morbidity and mortality in patients with prolonged and severe immune suppression such as following haematopoietic stem-cell transplantation. Consensus definitions, which allow categorisation of patients based on diagnostic criteria, are an important improvement in uniform registration of invasive mycoses in clinical trials. Prospective monitoring of high-risk patients for the circulating aspergillus cell-wall component galactomannan, results in earlier diagnosis in two-thirds of patients when compared with conventional diagnostic methods. High-resolution CT (HRCT) enables the lesions characteristic of invasive mycoses to be detected earlier and better than by chest radiograph. In addition, invasive mycoses cause characteristic lesions on the HRCT scan including the halo-sign and the air-crescent sign. The pre-emptive management strategy which combines monitoring of patients for surrogate markers with a HRCT scan appears to be a promising approach to the early identification and treatment of patients with invasive aspergillosis.

Aspergillosis↗
PubMed2005

Severely impaired IL-12/IL-18/IFNgamma axis in patients with hyper IgE syndrome.

BACKGROUND: Hyperimmunoglobulin E syndrome (HIES) is an inborn disorder characterized by recurrent skin and respiratory tract infections, skeletal abnormalities, chronic eczema and elevated serum IgE. The nature of the host defence defect has yet to be established. The aim of this study was to investigate whether activation of the interleukin-12/interleukin-18/interferon-gamma axis, known to be crucial for the activation of cellular immune responses, is impaired in patients with HIES. MATERIALS AND METHODS: Cytokine production capacity of seven HIES patients and seven healthy controls was investigated in whole-blood cultures stimulated with heat-killed Staphylococcus aureus, Candida albicans, or a combination of interleukin (IL)-12/IL-18. RESULTS: Interferon (IFN)gamma production, in addition to IFNgamma/IL-10 ratios, was 10-30-fold lower in the HIES patients compared with the healthy volunteers. In contrast TNF, IL-1beta and IL-8 production was normal. CONCLUSIONS: These data revealed a severe dysbalance towards a Th2 phenotype in HIES patients which is likely to contribute to the specific pattern of infection susceptibility characteristic to HIES.

Adult↗
PubMed2005

Cytokine responses to fungal pathogens in Kupffer Cells are Toll-like receptor 4 independent and mediated by tyrosine kinases.

Disseminated fungal infections are increasing. However, the interactions between the body's largest population of tissue macrophages, the Kupffer cells and the fungal pathogens are scarcely understood. The aim of this study was to examine the involvement of Toll-like receptor 4 (TLR4) signalling in cytokine production, using primary cultures of rat and murine Kupffer cells exposed to Aspergillus fumigatus and Candida albicans hyphae and conidia. All fungal components induced the release of tumour necrosis factor-alpha (TNF-alpha), but with delayed kinetics compared with lipopolysaccharide (LPS). Candida albicans was the most potent inducer of TNF-alpha protein and mRNA and the only inducer of interleukin-10 (IL-10) in rat Kupffer cells. All fungal components induced enhanced mRNA levels of macrophage inhibitory protein-2 (MIP-2) in the cells, similar to LPS. Inhibitors of Src tyrosine kinases added to cells prior to stimulation led to attenuation in the release of both TNF-alpha (60%, P < 0.05) and IL-10 (70%, P < 0.05) induced by C. albicans conidia but did not influence the LPS-mediated cytokine release. Murine Kupffer cells (C57BL/10J) also released TNF-alpha as well as the chemokines keratinocyte-derived chemokine (KC) and MIP-2 in response to fungal component. Surprisingly, Kupffer cells from TLR4-deficient C57BL/ScCr mice exhibited significantly enhanced production of KC and MIP-2 upon stimulation by fungal components compared with control littermates (P < 0.05). Our study demonstrates that Aspergillus and Candida components induce cytokine production in rat Kupffer cells and that the response to C. albicans conidia involves Src tyrosine kinases. The experiments with TLR4-deficient Kupffer cells suggest that the cytokine response in these cells to fungal component is not mediated by TLR4.

Animals↗
PubMed2005

National guidelines for the use of antibiotics in hospitalised adult patients: the SWAB guidelines revisited.

Since 1996, the Dutch Working Party on Antibiotic Policy (Stichting Werkgroep AntibioticaBeleid, SWAB) has been developing national guidelines for the use of antibiotics in hospitalised adult patients. As a result of both an inventory of the wishes of the users of these guidelines and the recently developed criteria for evidence-based guideline development, we have revised our format for the development of SWAB guidelines. By involving the members of the relevant professional societies and giving them the opportunity to comment on the guidelines at an early stage, we are aiming for a successful implementation of the guidelines in the hospitals.

Adult↗
PubMed2005

NOD2 3020insC mutation and the pathogenesis of Crohn's disease: impaired IL-1beta production points to a loss-of-function phenotype.

BACKGROUND: Mutations of the NOD2 gene increase the susceptibility of humans to Crohn's disease. NOD2 is a cytoplasmic receptor for the bacterial product peptidoglycan. There is considerable controversy in the literature whether the most common mutation in Crohn's disease, the 3020insC NOD2, leads to a loss of function, i.e. decreased cytokine production, or to the reverse, i.e. a gain of function. In previous papers we proposed the former, since we could show decreased cytokine production with a net proinflammatory status after exposure to muramyl dipeptide (MDP). METHODS: Because of recent data in the literature showing increased interleukin-beta (IL-1beta) production in mice with the corresponding NOD2 mutation, we investigated the production of this cytokine by cells of patients with Crohn's disease, either homozygous or heterozygous for the 3020insC mutation, and compared it with that of patients with Crohn's disease bearing the wild-type allele. RESULTS: A strongly decreased production of IL-1beta by peripheral mononuclear cells was found upon exposure to either peptidoglycan or peptidoglycan-derived MDP in homozygous patients bearing the 3020insC NOD2mutation. CONCLUSION: This sustains the hypothesis that the 3020insC mutation in the human NOD2 gene leads to a loss-of-function phenotype.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2005

Revised SWAB guidelines for antimicrobial therapy of community-acquired pneumonia.

The Dutch Working Party on Antibiotic Policy (SWAB) develops evidence-based guidelines, aimed at optimalisation of antibiotic use and limitation of the spread of antimicrobial resistance. A revision of the SWAB guideline for the treatment of community-acquired pneumonia (CAP), published in 1998, was considered necessary because of changes in resistance patterns and new insights into the epidemiology, diagnostics and treatment of CAP. In contrast to the former version, this guideline is transmural and has been drawn up according to the recommendations for evidence-based guideline development by a multidisciplinary committee consisting of experts from all relevant professional societies. The 'severity of disease' exhibited by the patient with pneumonia on admission is considered important for the choice of the optimum empirical treatment strategy. Severely ill patients are treated empirically with a drug directed against multiple potential pathogens, including Legionella spp. Classification according to 'severity of disease' can be accomplished with a validated scoring system (Pneumonia Severity Index or CURB-65 score) or pragmatically, based on the site of treatment: an outpatient setting, a clinical ward or an intensive care unit. The Legionella urine antigen test plays an important role in decisions on the choice of initial antibiotic treatment.

Anti-Bacterial Agents↗
PubMed2004

[Amphotericin B: the end of an era].

For 45 years, amphotericin B has been the drug of choice for the treatment of invasive mycoses. Because of its severe toxicity, lipid-associated formulations of amphotericin B have been developed. Although comparative trials are scarce, there appears to be no convincing advantage of these new formulations in terms of efficacy. The lipid-associated amphotericins are significantly less nephrotoxic than conventional amphotericin B, although there are major differences in the infusion-related toxicity of the various lipid-associated preparations. The current armamentarium of azoles and echinocandins for the treatment of invasive mycoses has only left a very minor role for both conventional and lipid-associated amphotericin B in the treatment of a few specific, rare mycoses.

Amphotericin B↗
PubMed2004

[New developments in antifungal therapy: fluconazole, itraconazole, voriconazole, caspofungin].

The azole antifungal voriconazole and the echinocandin caspofungin have recently become available for the treatment of invasive mycoses. Fluconazole remains the drug of choice for candidemia, except for infections with one of the resistent species such as Candida krusei and some strains of Candida glabrata. In these cases, as well as in patients who cannot tolerate azoles in connection with side effects or drug interactions, caspofungin is an attractive alternative. Voriconazole has become the drug of choice for severe invasive aspergillosis. Itraconazole is a good alternative for milder and chronic forms of aspergillosis. The use of conventional amphotericin B will be limited by the availability of the new drugs. In view of their high costs, the lipid-bound forms of amphotericin B will usually be given only as salvage therapy in case of failure, in patients who are unable to tolerate either conventional amphotericin or one of the newer agents, and for the treatment of zygomycosis.

Amphotericin B↗
PubMed2004

Recognition of fungal pathogens by Toll-like receptors.

Toll-like receptors (TLRs) have been identified as a major class of pattern-recognition receptors. Recognition of pathogen-associated molecular patterns by TLRs, either alone or in heterodimerization with other TLR or non-TLR receptors, induces signals responsible for the activation of the innate immune response. Recent studies have demonstrated a crucial involvement of TLRs in the recognition of fungal pathogens such as Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. Through the study of fungal infection in knock-out mice deficient in either TLRs or TLR-associated adaptor molecules, it became apparent that specific TLRs such as TLR2 and TLR4 play differential roles in the activation of the various arms of the innate immune response. Recent data also suggest that TLRs offer escape mechanisms to certain pathogenic microorganisms, especially through TLR2-driven induction of anti-inflammatory cytokines. These new data have substantially increased our knowledge of the recognition of fungal pathogens, and the study of TLRs remains one of the most active areas of research in the field of fungal infections.

Animals↗
PubMed2004

[Dutch Health Council advice 'Vaccination against pneumococcal infections in elderly persons and immunocompromised adults'].

The Dutch Health Council recently reported on the scientific desirability of making pneumococcal vaccination available to elderly persons and immunocompromised adults. On the basis of an assessment of the scientific evidence undertaken by the Dutch Cochrane Centre, the Council has concluded that extension of the current indication for pneumococcal vaccination is not scientifically justified. Vaccination is definitely recommended only for patients suffering from asplenia, sickle-cell anaemia or cerebrospinal fluid leakage. Whereas vaccination should be considered in individuals with certain other illnesses, vaccination is not recommended for people of advanced age or those diagnosed with solid tumours, diabetes mellitus, chronic respiratory disease or chronic heart failure.

Aged↗
PubMed2004

An open multicentre comparative study of the efficacy, safety and tolerance of fluconazole and itraconazole in the treatment of cancer patients with oropharyngeal candidiasis.

Oropharyngeal candidiasis is a frequent infection in cancer patients who receive cytotoxic drugs. In this study, the efficacy, safety and tolerance of fluconazole and itraconazole were compared in non-neutropenic cancer patients with oropharyngeal candidiasis. Of 279 patients who were randomised between the two treatment groups, 252 patients were considered to be eligible (126 in each group). The clinical cure rate was 74% for fluconazole and 62% for itraconazole (P=0.04, 95% Confidence Interval (CI): 0.5-23.3%). The mycological cure rate was 80% for fluconazole and 68% for itraconazole (P=0.03, 95% CI: 1.2-22.6%). The safety and tolerance profile of both drugs were comparable. This study has shown that in patients with cancer and oropharyngeal candidiasis, fluconazole has a significantly better clinical and mycological cure rate compared with itraconazole.

Adolescent↗