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| 2. |
- Ferngren, Gordon, et al.
(author)
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Epidemiological patterns of candidaemia : A comprehensive analysis over a decade
- 2024
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In: Mycoses. - : John Wiley & Sons. - 0933-7407 .- 1439-0507. ; 67:5, s. e13729-
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Journal article (peer-reviewed)abstract
- BACKGROUND: The prevalence of fungal bloodstream infections (BSI), especially candidaemia, has been increasing globally during the last decades. Fungal diagnosis is still challenging due to the slow growth of fungal microorganisms and need for special expertise. Fungal polymicrobial infections further complicate the diagnosis and extend the time required. Epidemiological data are vital to generate effective empirical treatment strategies.OBJECTIVES: The overall aim of this project is to describe the epidemiology of monomicrobial candidaemia and polymicrobial BSI, both with mixed fungaemia and with mixed Candida/bacterial BSIs.METHODS: We conducted a single-centre retrospective epidemiological study that encompasses 950,161 blood cultures during the years 2010 to 2020. The epidemiology of monomicrobial and polymicrobial candidaemia episodes were investigated from the electronic records.RESULTS: We found that 1334 candidaemia episodes were identified belonging to 1144 individual patients during 2010 to 2020. Candida albicans was the most prevalent species detected in candidaemia patients, representing 57.7% of these episodes. Nakaseomyces (Candida) glabrata and Candida parapsilosis complex showed an increasing trend compared to previous studies, whereas Candida albicans demonstrated a decrease. 19.8% of these episodes were polymicrobial and 17% presented with mixed Candida/bacterial BSIs while 2.8% were mixed fungaemia. C. albicans and N. glabrata were the most common combination (51.4%) in mixed fungaemia episodes. Enterococcus and Lactobacillus spp. were the most common bacteria isolated in mixed Candida/bacterial BSIs.CONCLUSIONS: Polymicrobial growth with candidaemia is common, mostly being mixed Candida/bacterial BSIs. C. albicans was detected in more than half of all the candidaemia patients however showed a decreasing trend in time, whereas an increase is noteworthy in C. parapsilosis complex and N. glabrata.
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| 3. |
- Halimi, Asif, et al.
(author)
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Isolation of pancreatic microbiota from cystic precursors of pancreatic cancer with intracellular growth and DNA damaging properties
- 2021
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In: Gut microbes. - : Taylor & Francis Group. - 1949-0976 .- 1949-0984. ; 13:1
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Journal article (peer-reviewed)abstract
- Emerging research suggests gut microbiome may play a role in pancreatic cancer initiation and progression, but cultivation of the cancer microbiome remains challenging. This pilot study aims to investigate the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Intra-operatively acquired pancreatic cyst fluid samples showed culture-positivity mainly in the intraductal papillary mucinous neoplasm (IPMN) group of lesions. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae, but also Granulicatella adiacens and Enterococcus faecalis, demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models. Pathogenic properties include intracellular survival capability, cell death induction, or causing DNA double-strand breaks in the surviving cells resembling genotoxic effects. This study provides new insights into the role of the pancreatic microbiota in the intriguing link between pancreatic cystic lesions and cancer.
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| 4. |
- Henning, Claes, et al.
(author)
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Detailed analysis of the characteristics of sample volume in blood culture bottles
- 2019
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In: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 57:8
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Journal article (peer-reviewed)abstract
- Blood volume is the most important variable, for detection of microorganisms in blood cultures (BC). Most standards recommend 40-60 ml blood, collected in several BC bottles filled up to 10 ml. We measured blood volume in individual BC bottles, and analysed the association of hospital, bottle type, day of the week, daily sampling time, and age and gender of the patient, with sampling volume and BC result. The variation in blood volume per BC bottle was analysed in a mixed linear model using hospital, bottle type, weekday, sampling time, age and gender as fixed factors, and patient ID and episode as random factors to control for repetitive sampling of individual patients. Only 18 % of all bottles were filled with the recommended 8-10 ml, and 47 % were filled with less than 8 ml. The mean (±SE) volume was larger in positive 9.09 (±0.15) compared to negative bottles 8.47 (±0.07) (p<0.001). Blood volume was larger in BacT/ALERT-FA Plus than in -FN Plus BC bottles (p<0.001). There was significantly lower volumes collected during the night (p<0.001). The volume of blood collected decreased significantly with increasing patient age (p<0.001). Larger volumes were collected from males compared to females, 8.78 (±0.06) vs. 8.36 (±0.06) ml (mean ± SE) respectively (p<0.001). The odds of detecting a positive patient increases with 13 % for each additional ml blood drawn. Our results show that we need to work actively with development of blood sampling routines to overcome age and gender effects, and to optimize blood sampling volumes.
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| 5. |
- Henning, Claes, et al.
(author)
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Rekommenderade metoder Diagnostik av infektioner i blod orsakade av bakterier och svamp
- 2024
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Other publication (other academic/artistic)abstract
- I detta dokument beskrivs rekommenderade metoder för blododling inkluderat fungemi(svampinfektion i blod) samt metodik för diagnostik av endokardit och misstanke om infektion relaterad till kärlkatetrar. Rekommendationerna är baserade på internationella riktlinjer och relevant vetenskaplig litteratur. Där det finns icke tillräcklig vetenskapligt stöd har arbetsgruppen antingen avstått från en rekommendation eller givit en rekommendation baserad på de ingående medlemmarnas erfarenhet och kunnande.
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| 6. |
- Iseri, Emre, PhD, et al.
(author)
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Performance of an innovative culture-based digital dipstick for detection of bacteriuria
- 2023
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In: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497.
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Journal article (peer-reviewed)abstract
- UTI-lizer is a recent digital format for easy-to-use culture-based detection, preliminary identification, and quantification of bacteria in urine at the point of care (PoC). This study aimed to evaluate the diagnostic accuracy of UTI-lizer tests for detection of bacteriuria caused by five common bacterial species: Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabilis, and Staphylococcus saprophyticus. We evaluated the accuracy of UTI-lizer tests by comparing test results of UTI-lizer with those of current standard bacterial culture-based diagnostics in clinical microbiology laboratories in a retrospective and a prospective study. Comparator methods were classical bacterial culture in combination with matrix-assisted laser desorption/ionization-time of flight mass spectrometry mediated bacterial identification. In the retrospective study, we tested 104 urine samples with in-panel microorganisms, plain urethral microbiota, and culture-negative samples. In the prospective study, we used 137 urine samples within 10 hours of their collection at general practitioner clinics. The retrospective study demonstrated 100% sensitivity and specificity in the detection of bacteriuria, and 98.6% sensitivity and 96.8% specificity in identifying primary pathogens with UTI-lizer when compared to clinical standards. S. saprophyticus and E. coli could not be distinguished. The combined nitrite and esterase test predicted the presence of bacteriuria in only 36.5% of cases. The prospective study demonstrated 100% sensitivity and 89.6% specificity in the detection of significant bacteriuria for in-panel microorganisms with a coverage rate of 88.3% (121/137). This study indicates that digital dipsticks are a promising alternative for the detection of the five main pathogens that cause the vast majority of urinary tract infections (UTIs). The results demonstrate that digital dipsticks have the potential to uniquely provide—in primary care or at the point of care—a UTI diagnostic quality on par with that of current gold-standard testing. The ease of testing, rapid test handling time, and time to result as well as simple test equipment make digital dipsticks an attractive solution for decentralized testing for bacteriuria and with that improvement in UTI diagnostics. These results motivate future studies to validate the use of UTI-lizer at the PoC setting.
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| 7. |
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| 8. |
- Krifors, Anders, et al.
(author)
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Combining T2Bacteria and T2Candida Panels for Diagnosing Intra-Abdominal Infections : A Prospective Multicenter Study
- 2022
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In: JOURNAL OF FUNGI. - : MDPI. - 2309-608X. ; 8:8
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Journal article (peer-reviewed)abstract
- The T2Bacteria panel is a direct-from-blood assay that delivers rapid results, targeting E. coli, S. aureus, K. pneumoniae, A. baumanii, P. aeruginosa, and E. faecium (ESKAPE pathogens). In this study, T2Bacteria and T2Candida (targeting C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis) were evaluated in parallel with blood cultures in 101 consecutive surgical patients with suspected intra-abdominal infection admitted to the intensive care unit or high dependency unit. Fifteen patients had bacteremia, with T2Bacteria correctly identifying all on-panel (n = 8) pathogens. T2Bacteria was positive in 19 additional patients, 11 of whom had supportive cultures from other normally sterile sites (newly inserted drains, perioperative cultures or blood cultures) within seven days. Six of these eleven patients (55%) received broad-spectrum antibiotics at the sampling time. T2Candida identified the two cases of blood-culture-positive candidemia and was positive in seven additional patients, three of whom were confirmed to have intra-abdominal candidiasis. Of four patients with concurrent T2Bacteria and T2Candida positivity, only one patient had positive blood cultures (candidemia), while three out of four patients had supporting microbiological evidence of a mixed infection. T2Bacteria and T2Candida were fast and accurate in diagnosing on-panel bloodstream infections, and T2Bacteria was able to detect culture-negative intra-abdominal infections.
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| 9. |
- Larsson, Anna, et al.
(author)
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Single-site sampling versus multi-site sampling for blood cultures; A retrospective clinical study
- 2022
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In: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 60:2
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Journal article (peer-reviewed)abstract
- Objectives The performance of blood cultures (BC) relies on optimal sampling. Sepsis guidelines do not specify which sampling protocol to use, but recommend two sets of BC bottles, each set containing one aerobic and one anaerobic bottle. For the single-site sampling (SSS) protocol, only one venipuncture is performed for all four bottles. The predominating multi-site sampling (MSS) protocol implies that BC bottles are collected from two separate venipuncture sites. The aim of this study was to compare SSS and MSS. Primary outcomes were number of BC sets collected, sample volume and diagnostic performance. Methods This was a retrospective clinical study comparing BC results in an emergency department before and after changing the sampling protocol to SSS from MSS. All BC samples were incubated in the BacT/ALERT BC system. Results The analysis included 5,248 patients before and 5,364 patients after the implementation of SSS. There was a significantly higher proportion of positive BCs sampled with SSS compared to MSS, 1,049/5,364 (19.56%) and 932/5,248 (17.76%) respectively (P=0.018). This difference was due to a higher proportion of solitary BC sets (two BC bottles) in MSS. Analyzing only patients with the recommended four BC bottles, there was no difference in positivity. SSS had a higher proportion of BC bottles with the recommended sample volumes of 8-12 ml than MSS (P<0.001). Conclusions Changing the sampling protocol to SSS from MSS resulted in higher positivity rates, higher sample volume and fewer solitary BC sets. These advantages of SSS should be considered in future sepsis guidelines.
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| 10. |
- Manoil, Daniel, et al.
(author)
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Photo-oxidative stress response and virulence traits are co-regulated in E. faecalis after antimicrobial photodynamic therapy
- 2022
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In: Journal of Photochemistry and Photobiology. B. - : Elsevier. - 1011-1344 .- 1873-2682. ; 234
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Journal article (peer-reviewed)abstract
- Knowledge of photo-oxidative stress responses in bacteria that survive antimicrobial photodynamic therapy (aPDT) is scarce. Whereas aPDT is attracting growing clinical interest, subsequent stress responses are crucial to evaluate as they may lead to the up-regulation of pathogenic traits. Here, we aimed to assess transcriptional responses to sublethal aPDT-stress and identify potential connections with virulence-related genes. Six Enterococcus faecalis strains were investigated; ATCC 29212, three dental root-canal isolates labelled UmID1, UmID2 and UmID3 and two vancomycin-resistant isolates labelled A1 and A2. TMPyP was employed as a photosensitiser. A viability dose-response curve to increasing concentrations of TMPyP was determined by culture plating. Differential expression of genes involved in oxidative stress responses (dps and hypR), general stress responses (dnaK, sigma-factorV and relA), virulence-related genes (ace, fsrC and gelE) and vancomycin-resistance (vanA) was assessed by reverse-transcription qPCR. TMPyP-mediated aPDT inactivated all strains with comparable efficiencies. TMPyP at 0.015 μM was selected to induce sublethal photo-oxidative stress. Despite heterogeneities in gene expression between strains, transcriptional profiles revealed up-regulations of transcripts dps, hypR as well as dnaK and sigma factorV after exposure to TMPyP alone and to light-irradiated TMPyP. Specifically, the alternative sigma factorV reached up to 39 ± 113-fold (median ± IQR) (p = 0.0369) in strain A2. Up-regulation of the quorum sensing operon, fsr, and its downstream virulence-related gelatinase gelE were also observed in strains ATCC-29212, A1, A2 and UmID3. Finally, photo-oxidative stress induced vanA-type vancomycin-resistance gene in both carrier isolates, reaching up to 3.3 ± 17-fold in strain A2 (p = 0.015). These findings indicate that, while aPDT successfully inactivates vancomycin-resistant and naïve strains of E. faecalis, subpopulations of surviving cells respond by co-ordinately up-regulating a network of genes involved in stress survival and virulence. This includes the induction of vancomycin-resistance genes in carrier isolates. These data may provide the mechanistic basis to circumvent bacterial responses and improve future clinical protocols.
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| 11. |
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| 12. |
- Olofsson, Emma, 1981-, et al.
(author)
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Evaluation of the Sofia S. pneumoniae FIA for Detection of Pneumococcal Antigen in Patients with Bloodstream Infection
- 2019
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In: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 57:8
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Journal article (peer-reviewed)abstract
- The usefulness of pneumococcal urinary antigen tests (UATs) in severe pneumococcal infection relies heavily on the performance in bacteremic patients. Fluorescence technology and automatic reading of test results may improve UAT performance. We evaluated the automatically read Sofia S. pneumoniae FIA for diagnosing pneumococcal bloodstream infection (BSI) in hospitalized adult patients. First, the Sofia FIA was evaluated on 97 patients with pneumococcal (n = 47) and nonpneumococcal (n = 50) BSI and compared with results by the visually read BinaxNOW S. pneumoniae immunochromatographic test (ICT) and ImmuView S. pneumoniae and Legionella pneumophila ICT. In four cases (4.1%), the Sofia FIA showed invalid test results, three of which showed invalid results by the ImmuView ICT previously. Based on 93 valid cases, the Sofia FIA showed similar sensitivity (for both comparisons: 68% versus 62%; P = 0.45) and specificity (for both comparisons: 91% versus 93%; P = 1.00) as the visually read UATs. Second, the Sofia FIA was prospectively evaluated on 82 consecutive nonfrozen urine samples, detecting pneumococcal antigen in 10 of 14 (sensitivity, 71%) pneumococcal BSI patients, similarly to the visually and automatically read BinaxNOW ICT (both 12 of 14; sensitivity, 86%; P = 0.50). Of five nonpneumococcal BSI cases, the Sofia FIA showed an invalid test result in one case, but no positive UAT results were obtained. Thus, the sensitivity and specificity of the Sofia FIA were similar to the performance rates of other UATs in patients with BSI, but invalid test results are of concern for the usefulness in pneumococcal BSI.
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| 13. |
- Strålin, Kristoffer, et al.
(author)
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Performance of PCR/electrospray ionization-mass spectrometry on whole blood for detection of bloodstream microorganisms in patients with suspected sepsis
- 2020
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In: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 58:9, s. e01860-19
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Journal article (peer-reviewed)abstract
- Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the USA (n=13) and Europe (n=3). First, on 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true positive and 97.2% true negative results. Secondly, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC+/PCR/ESI-MS-, 4.3%; BC+/PCR/ESI-MS+, 10.3%; BC-/PCR/ESI-MS+, 15.3%; and BC-/PCR/ESI-MS-, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and Candida species, 83%. The specificities were > 94% for all individual species. Patients treated with prior antimicrobial medications (n=603) had significantly increased PCR/ESI-MS positivity rates compared with patients without prior antimicrobial treatment, 31% vs 22% (p<0.0001), with pronounced differences for Gram-negative bacteria and Candida species. In conclusion, PCR/ESI-MS showed excellent performance on contrived samples. On clinical samples, it showed high specificities, moderately high sensitivities for Gram-negative bacteria and Candida species, and elevated positivity rates during antimicrobial treatment. These promising results encourage further development of molecular diagnostics on whole blood for detection of bloodstream microorganisms in sepsis.
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| 14. |
- Wong, Alicia Yoke Wei, et al.
(author)
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Comparison of Four Streptococcus pneumoniae Urinary Antigen Tests Using Automated Readers
- 2021
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In: Microorganisms. - : MDPI. - 2076-2607. ; 9:4
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Journal article (peer-reviewed)abstract
- Streptococcus pneumoniae urinary antigen tests (UATs) may be interpreted using automatic readers to potentially automate sample incubation and provide standardized results reading. Here, we evaluated four UATs the BinaxNOW S. pneumoniae Antigen Card (Abbott, Chicago, IL, USA), ImmuView S. pneumoniae and Legionella (SSI Diagnostica, Hillerød, Denmark), STANDARD F S. pneumoniae Ag FIA (SD Biosensor, Gyeonggi, South Korea), and Sofia S. pneumoniae FIA (Quidel Corporation, San Diego, CA, USA) with their respective benchtop readers for their ability to detect S. pneumoniae urinary antigen. We found that these assays had a sensitivity of 76.9–86.5%, and specificity of 84.2–89.7%, with no significant difference found among the four UATs. The assays had a high level of agreement with each other, with 84.5% of samples testing consistently across all four assays. The automatically and visually read test results from the two immunochromatographic assays, BinaxNOW and ImmuView, were compared and showed excellent agreement between the two types of reading. Immunofluorescent-based assays, Sofia and STANDARD F, had significantly less time to detect compared to the two immunochromatographic assays due to having less assay setup procedures and shorter sample incubation times. In conclusion, the four UATs performed similarly in the detection of S. pneumoniae urinary antigen, and readers can bring increased flexibility to running UATs in the clinical routine.
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| 15. |
- Wong, Alicia Y. W., et al.
(author)
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Evaluation of Four Lateral Flow Assays for the Detection of Legionella Urinary Antigen
- 2021
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In: Microorganisms. - : MDPI. - 2076-2607. ; 9:3
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Journal article (peer-reviewed)abstract
- Urinary antigen tests (UATs) are often used to diagnose Legionnaires' disease as they are rapid and easy to perform on readily obtainable urine samples without the need for specialized skills compared to conventional methods. Recently developed automated readers for UATs may provide objective results interpretation, especially in cases of weak result bands. Using 53 defined patient urine samples, we evaluated the performance of the BinaxNOW Legionella Antigen Card (Abbott), ImmuView S. pneumoniae and Legionella (SSI Diagnostica), STANDARD F Legionella Ag FIA (SD Biosensor), and Sofia Legionella FIA (Quidel) simultaneously with their respective automated readers. Automatic and visual interpretation of result bands were also compared for the immunochromatography-based BinaxNOW and ImmuView UATs. Overall sensitivity and specificity of Legionella UATs were 53.9-61.5% and 90.0-94.9%, respectively. All four UATs successfully detected all samples from L. pneumophila serogroup 1-positive patients, but most failed to detect samples for Legionella spp., or other serogroups. Automatic results interpretation of results was found to be mostly concordant with visual results reading. In conclusion, the performance of the four UATs were similar to each other in the detection of Legionella urinary antigen with no major difference between automated or visual results reading.
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| 16. |
- Özenci, Volkan
(author)
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Immune regulation in multiple sclerosis : cytokines and metalloproteinases
- 2000
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Doctoral thesis (other academic/artistic)abstract
- Immunological mechanisms play a central role in the pathogenesis sclerosis (MS). In this study two groups of related immune variables are cytokines and metalloproteinases (MMPs), which regulate each other's production and activation. Cytokines play key role in pathogenesis and treatments of Cytokines are regulatory proteins secreted by a variety of cells. The pleiotropic action of cytokines include numerous effects on cells of the immune modulating immune responses. Cytokine receptors are crucial for the net effect of cytokines. The balance between Th1 and Th2 type cytokines might determine whether the immune response in MS is detrimental or beneficial. MMPs are a group of endopeptidases that degrade extracellular pro mechanisms in the genesis of inflammatory demyelination, such as recruitment, blood-brain barrier breakdown and myelin destruction are con be MMP-dependent processes. Aims of the study: 1. To investigate the levels of cytokine secreting blood and cerebrospinal fluid mononuclear cells (MNC) in patients with MS and controls; 2. To define further the cytokine disbalance in MS by examining the levels of cytokine receptors that are important in the net effect of cytokine function; 3. To study the levels of blood and CSF MNC in MS expressing mRNA of MMPs and their inhibitors; and 4. To examine the effects of IFN-[beta] on cytokines and MMPs in MS. Results: MS is associated with increased numbers of IL-6 and TNF-[alpha] secreting blood MNC and decreased numbers of IL-10 secreting cells compared to healthy subjects. In CSF, similar numbers of IL-6 and IL-10 secreting cells were observed in patients with MS and other neurological diseases (OND). Patients with MS also had higher levels of MMP-3, MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA expressing blood MNC compared to controls. When patients with MS examined before vs. during 1 year of treatment with IFN-[beta], treatment resulted in decreased numbers of IL-6 and TNF-[alpha] secreting MNC and of MMP-3 and MMP mRNA expressing MNC compared to pretreatment levels. On the contrary, numbers of IL-10 secreting MNC and TIMP-1 mRNA expressing MNC were augmented IFN-[beta] therapy. IL-12 is a key cytokine for the development of Th1 type of immune response. ELISPOT assays were adopted to detect IL-12 secreting cells. In intracellular staining of IL-12 was measured by flow cytometry. Numbers of secreting blood MNC correlated with IL-12 positive blood MNC detected by flow cytometry. Utilizing IL-12 ELISPOT assays, elevated numbers of IL-12 secreting blood MNC were observed after stimulation with TNF-[alpha], IFN-[gamma], LPS, LPS+TNF-[alpha] or LPS+IFN-[gamma] compared to cultures without stimulation. When patients with MS were compared with controls, no difference was observed for numbers of IL-12 secreting blood MNC. In contrast, levels of IL-12 receptor (R)[beta]1 and -02 expressing T cells are higher in MS compared to controls, suggesting an elevated net effect of IL-12 in MS. Conclusion: MS is associated with a disbalance of cytokines and of MMPs that may contribute to the pathogenesis of the disease. IFN-[beta] therapy seems to normalize altered levels of cytokines and MMPs observed in MS.
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