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- Augustinsson (Nilsdotter-Augustinsson), Åsa, 1962-, et al.
(author)
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Interaction of staphylococcus epidermidis from infected hip prostheses with neutrophil granulocytes
- 2001
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 33:6, s. 408-412
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Journal article (peer-reviewed)abstract
- This study focuses on the interaction of Staphylococcus epidermis isolated from granulation tissue covering infected hip prostheses and neutrophil granulocytes. Bacterial strains isolated from normal flora were used as controls. The bacteria were well characterized with routine methods and further characterized with random amplified polymorphic DNA analyses and slime tests. Phagocytosis and chemiluminescence (CL) assays were used in the neutrophil interaction studies. The prostheses strains were ingested to a lesser extent than strains from normal flora (p ≤ 0.001). There was no significant difference between the prostheses strains and the normal flora strains in terms of total CL response. However, the extracellular CL response from the neutrophils was lower in comparison with the normal flora when interacting with the prostheses strains. The results of this study support the notion that S. epidermidis strains isolated from infected hip prostheses have an enhanced capacity to resist phagocytosis and that most of these strains elicit a reduced inflammatory response, measured as the production of extracellular oxidative metabolites from the neutrophils, compared to normal flora.
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| 2. |
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| 3. |
- Nilsdotter-Augustinsson, Åsa, 1962-, et al.
(author)
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Adherence of Staphylococcus epidermidis to extracellular matrix proteins and effects of fibrinogen-bound bacteria on oxidase activity and apoptosis in neutrophils
- 2005
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In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 113:5, s. 361-373
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Journal article (peer-reviewed)abstract
- Staphylococcus epidermidis often causes foreign-body infections such as those associated with hip prostheses, but the underlying pathogenic mechanisms are not fully understood. We performed spectrophotometry to study the ability of S. epidermidis to bind to immobilised fibrinogen, fibronectin, vitronectin, and collagen. The strains were isolated from infected hip prostheses or from normal flora and the well-known protein-binding strain Staphylococcus aureus Cowan was used as positive control. We also analysed the interaction between neutrophils and a fibrinogen-bound prosthesis-derived strain of S. epidermidisby measuring chemiluminescence to determine the neutrophil oxidative response and binding of annexin V to indicate neutrophil apoptosis. We found that binding of S. epidermidis to extracellular matrix proteins varied under different growth conditions, and that prosthesis isolates adhered better to vitronectin than did strains from normal flora. The oxidative response caused by fibrinogen-bound S. epidermidis was not above the background level, which was in marked contrast to the distinct response induced by fibrinogen-associated S. aureus Cowan. Furthermore, fibrinogen-adhering S. epidermidis retarded neutrophil apoptosis. We conclude that surface-bound S. epidermidis induces only a weak inflammatory response, which in combination with the ability of the adherent bacteria to retard neutrophil apoptosis may contribute to low-grade inflammation and loosening of prostheses.
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| 4. |
- Nilsdotter-Augustinsson, Åsa, 1962-, et al.
(author)
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Staphylococcus aureus, but not Staphylococcus epidermidis, modulates the oxidative response and induces apoptosis in human neutrophils
- 2004
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In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 112:2, s. 109-118
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Journal article (peer-reviewed)abstract
- S. epidermidis is the most common isolate in foreign body infections. The aim of this study was to understand why S. epidermidis causes silent biomaterial infections. In view of the divergent inflammatory responses S. epidermidis and S. aureus cause in patients, we analyzed how they differ when interacting with human neutrophils. Neutrophils interacting with S. epidermidis strains isolated either from granulation tissue covering infected hip prostheses or from normal skin flora were tested by measuring the oxidative response as chemiluminescence and apoptosis as annexin V binding. Different S. aureus strains were tested in parallel. All S. epidermidis tested were unable to modulate the oxidative reaction in response to formyl-methionyl-leucyl-phenylalanine (fMLP) and did not provoke, but rather inhibited, apoptosis. In contrast, some S. aureus strains enhanced the oxidative reaction, and this priming capacity was linked to p38-mitogen-activated-protein-kinase (p38-MAPK) activation and induction of apoptosis. Our results may explain why S. epidermidis is a weak inducer of inflammation compared to S. aureus, and therefore responsible for the indolent and chronic course of S. epidermidis biomaterial infections.
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| 7. |
- Enocsson, Helena, et al.
(author)
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Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19
- 2021
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In: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Journal article (peer-reviewed)abstract
- Background: Efficient healthcare based on prognostic variables in hospitalised patients with COVID-19 could reduce the risk of complications and death. Recently, soluble urokinase Plasminogen Activator Receptor (suPAR) was shown to predict respiratory failure, kidney injury, and clinical outcome in patients with SARS-CoV-2 infection. The aim of this study was to investigate the value of suPAR as a prognostic tool, in comparison with other variables, regarding disease severity and length of hospital stay in patients with COVID-19.Patients and Methods: Individuals hospitalised with COVID-19 (40 males, 20 females; median age 57.5 years) with a median symptom duration of 10 days and matched, healthy controls (n = 30) were included. Admission levels of suPAR were measured in serum by enzyme-linked immunosorbent assay. Blood cell counts, C-reactive protein (CRP) levels, lactate dehydrogenase (LDH), plasma creatinine and estimated glomerular filtration rates were analysed and oxygen demand, level of care and length of hospitalisation recorded.Results: Patients had significantly higher suPAR levels compared to controls (P < 0.001). Levels were higher in severely/critically (median 6.6 ng/mL) compared with moderately ill patients (median 5.0 ng/mL; P = 0.002). In addition, suPAR levels correlated with length of hospitalisation (rho = 0.35; P = 0.006). Besides suPAR, LDH, CRP, neutrophil count, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratio, body mass index and chronic renal failure were discriminators of COVID-19 severity and/or predictors of length of hospitalisation.Conclusion: Admission levels of suPAR were higher in patients who developed severe/critical COVID-19 and associated with length of hospital stay. In addition, we showed that suPAR functioned as an independent predictor of COVID-19 disease severity.
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| 8. |
- Hopkins, Francis R., et al.
(author)
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Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19
- 2023
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Journal article (peer-reviewed)abstract
- Introduction: After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.Methods: Here, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.Results: We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.Conclusion: By exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.
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| 9. |
- Nilsdotter-Augustinsson, Åsa, 1962-
(author)
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Gastroenterit
- 2022. - 2
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In: Infektionsmedicin. - Lund : Studentlitteratur AB. - 9789144153308 ; , s. 55-68
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Book chapter (other academic/artistic)
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| 10. |
- Nilsdotter-Augustinsson, Åsa, 1962-
(author)
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Handläggning av infektioner vid ortopediska implantat en utmaning för vården
- 2019
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In: Läkartidningen. - Stockholm. - 0023-7205 .- 1652-7518. ; 116:FR6C, s. 1-6
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Journal article (peer-reviewed)abstract
- The Swedish National Guidelines for Bone and Joint Infections were revised during 2018. The work was carried out on behalf of the Swedish Society for Infectious Diseases. The study group consists of senior consultants in infectious diseases, supported by specialists in orthopedic surgery, clinical microbiology and allergology when needed. The study group emphasizes that implant associated infections are challenging and requires multidisciplinary cooperation, including, but not limited to, specialists in orthopedic surgery, infectious diseases, clinical microbiology and radiology for optimal treatment results. All aspects of the clinical management are equally important; selecting the optimal antibiotic prophylaxis in arthroplasty as well as fracture surgery, early diagnosis of infection, adequate treatment, follow-up, and finally a structured evaluation of outcome. Profound and updated knowledge of treatment of biofilm related infection is necessary to achieve optimal results in patients with implant-associated infections. Future challenges include improved decision support for combining surgical treatment with selection of proper antibiotics, as well as management of antibiotic resistance, drug-drug interactions and adverse effects of antibiotic treatment.
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| 11. |
- Ridberg, Sara, et al.
(author)
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Cutibacterium acnes (formerly Propionibacterium acnes) isolated from prosthetic joint infections is less susceptible to oxacillin than to benzylpenicillin
- 2019
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In: Journal of bone and joint infection. - Sydney, NSW, Australia : Ivyspring International Publisher. - 2206-3552. ; 4:3, s. 106-110
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Journal article (peer-reviewed)abstract
- Introduction: The frequency of prosthetic joint infections (PJIs) due to Cutibacterium acnes (formerly Propionibacterium acnes) is increasing, especially shoulder PJIs. The recommended antibiotic prophylaxis for hip and knee arthroplasties is beta-lactam antibiotics, predominantly cephalosporins. However, for example in Sweden, isoxazolyl-penicillin cloxacillin is used. No specific recommendations for shoulder arthroplasties are available. The aim of the present study was to determine the minimum inhibitory concentration (MIC) values for different antibiotics for C. acnes; and, more specifically, to compare the MIC values for benzylpenicillin and oxacillin.Materials and methods: Minimum inhibitory concentration (MIC) values for nine different antibiotic agents were obtained by gradient test (Etest) using strains of C. acnes (n= 57) isolated from PJIs from shoulders (n=31), hips (n=21), and knees (n=5).Results: All isolates had low MIC values for most of the tested antibiotic agents, and showed a wild type MIC distribution. The exception was clindamycin with 9% of the isolates displaying decreased susceptibility. The MIC values obtained for benzylpenicillin were significantly lower than the MIC values for isoxazolyl-penicillin (oxacillin).Conclusion: These in vitro results indicate that benzylpenicillin might be a more effective prophylactic treatment to prevent shoulder PJIs caused by C. acnes. However, further studies on the subject are needed, and the effectiveness of the prophylactic treatment should be evaluated using randomized controlled studies and/or register-based studies.
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| 12. |
- Sune, Dan, et al.
(author)
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Optimization of 16S rRNA gene analysis for use in the diagnostic clinical microbiology service
- 2020
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In: Journal of Microbiological Methods. - : ELSEVIER. - 0167-7012 .- 1872-8359. ; 170
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Journal article (peer-reviewed)abstract
- Broad-range amplification and sequencing of the 16S rRNA gene, directly from clinical samples, is a method that potentially allows detection of any cultivable or non-cultivable bacteria. However, the method is prone to false positive results due to PCR contamination. Another concern is the human DNA abundance compared to bacterial DNA in samples from sterile sites. Those factors may decrease the sensitivity and specificity of the assay and can complicate the analysis and interpretation of the results. The objective of this prospective study was to try to avoid the most common pitfalls, mentioned above, and develop a molecular 16S assay with a high clinical sensitivity and specificity. Fifty-six consecutive tissue samples from patients with suspected deep infections were extracted by 3 different DNA-extraction methods; two based on a principle of bacterial DNA enrichment, and one conventional DNA extraction method. We compared three primer pairs, including both conventional and DPO principle, targeting different variable regions of the 16S rRNA gene. Results from routine tissue culture were used as reference. Clinical data was recorded from patient charts and analyzed in parallel. Of a total of 56 samples, collected from 39 patients, 70% (39 samples) were assessed as true infections by analysis of clinical data. Bacterial enrichment extraction increased sensitivity from 54% to 72%. The 2 sets of primer pairs defining region V1-V3 and V3-V4, showed similar sensitivity, but DPO-primers resulted in better specificity, i.e. less contaminations. The primer pairs covering V1-V8 show significantly lower sensitivity (p amp;lt; .001) than V1-V3 and V3-V4. Optimizing extraction protocols and choice of primers can increase the sensitivity and specificity of a molecular 16S-analysis, rendering a valuable complement to tissue culture.
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| 13. |
- Wågström, Per, 1967-
(author)
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Clinical and immunological aspects of IgG subclass deficiency : Predictors for the need of immunoglobulin replacement therapy
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Background: Predominantly antibody deficiencies (PAD) are inborn errors of immunity, and associate with increased susceptibility to infections. Life-long immunoglobulin replacement therapy (IgRT) is introduced based on Ig-levels and the frequencies and severity of infections. The subgroup of PAD with immunoglobulin G subclass deficiency (IgGsd) is often less severe and the need of IgRT in these patients is unclear. Often many years pass before IgGsd is diagnosed, and repeated respiratory tract infections risk to confer lung tissue damage. The Swedish standard regimen in IgGsd is IgRT during 18 months followed by a period of discontinuation in order to evaluate the effect and restart it, if infections reoccur. It is a challenge to identify the subgroup of IgGsd-individuals in need of life-long treatment, and early reliable markers are warranted. Aim: The aim of this thesis was to identify clinical and laboratory factors predicting the need of long-term IgRT in IgGsd and evaluate its effects on immunological functions. Results: In paper I, the established clinical warning sign that is used to identify individuals with PAD in need of IgRT, was evaluated regarding the accuracy to identify IgGsd in a primary care register with data from 350,000 visits due to respiratory tract infections. The predictive value was low and according to medical records, a primary immunodeficiency was rarely suspected. In paper II, a lower frequency of homozygosity for the high affinity IgG receptor FcγRIIa H/H131 were found in IgGsd compared to controls. The finding supports the hypothesis that FcγR-polymorphisms may be of importance for susceptibility to infections in IgGsd and may have impact on the need of IgRT. In paper III, patient reported outcome showed that severe fatigue and low health related quality of life associated with the need of life-long IgRT. Systemic inflammation is known to associate with fatigue and in paper III and IV extensive immunophenotyping was performed when on and off IgRT. IgGsd patients were characterized by dysregulated plasma protein profiles enriched for factors associated with interleukin 10 signaling that were unaffected by IgRT. Among circulating immune cells, decreased proportions of activated B- and T cell subsets, as well as regulatory T cells, were found and partly restored during IgRT. Individuals needing life-long IgRT had a lower prevalence of protective pneumococcal specific IgG against 21 tested capsular serotypes. Co-morbidity with autoimmunity, atopy, lung disease and other factors such as higher age and occupation also associated to the need of IgRT. Conclusion: IgGsd patients were characterized by increased systemic inflammation, which was unaffected by IgRT. Decreased activation of lymphocyte subsets was partly restored during IgRT. Severe fatigue, protective IgG levels against a low number of pneumococcal serotypes, especially in conjunction with comorbidities were associated with the need for IgRT. Overall, no factor alone could predict the need of life-long IgRT.
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