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  • 1
    Online Resource
    Online Resource
    Performance of the beta-glucan test for the diagnosis of invasive fusariosis and scedosporiosis: a meta-analysis
    Oxford University Press (OUP) ; 2023
    In:  Medical Mycology Vol. 61, No. 7 ( 2023-07-06)
    Details
    In: Medical Mycology, Oxford University Press (OUP), Vol. 61, No. 7 ( 2023-07-06)
    Abstract: The (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold infections (IMI) in patients with hematologic cancer or other immunosuppressive conditions. However, its use is limited by modest sensitivity/specificity, inability to differentiate between fungal pathogens, and lack of detection of mucormycosis. Data about BDG performance for other relevant IMI, such as invasive fusariosis (IF) and invasive scedosporiosis/lomentosporiosis (IS) are scarce. The objective of this study was to assess the sensitivity of BDG for the diagnosis of IF and IS through systematic literature review and meta-analysis. Immunosuppressed patients diagnosed with proven or probable IF and IS, with interpretable BDG data were eligible. A total of 73 IF and 27 IS cases were included. The sensitivity of BDG for IF and IS diagnosis was 76.7% and 81.5%, respectively. In comparison, the sensitivity of serum galactomannan for IF was 27%. Importantly, BDG positivity preceded the diagnosis by conventional methods (culture or histopathology) in 73% and 94% of IF and IS cases, respectively. Specificity was not assessed because of lacking data. In conclusion, BDG testing may be useful in patients with suspected IF or IS. Combining BDG and galactomannan testing may also help differentiating between the different types of IMI.
    Type of Medium: Online Resource
    ISSN: 1369-3786 , 1460-2709
    URL: Article
    DOI: 10.1093/mmy/myad061
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2020733-5
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  • 2
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    Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients
    Oxford University Press (OUP) ; 2019
    In:  Journal of Antimicrobial Chemotherapy Vol. 74, No. 9 ( 2019-09-01), p. 2759-2766
    Details
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 74, No. 9 ( 2019-09-01), p. 2759-2766
    Abstract: Increasing resistance of Aspergillus fumigatus to triazoles in high-risk populations is a concern. Its impact on mortality is not well understood, but rates from 50% to 100% have been reported. Objectives To determine the prevalence of voriconazole-resistant A. fumigatus invasive aspergillosis (IA) and its associated mortality in a large multicentre cohort of haematology patients with culture-positive IA. Methods We performed a multicentre retrospective study, in which outcomes of culture-positive haematology patients with proven/probable IA were analysed. Patients were stratified based on the voriconazole susceptibility of their isolates (EUCAST broth microdilution test). Mycological and clinical data were compared, along with survival at 6 and 12 weeks. Results We identified 129 A. fumigatus culture-positive proven or probable IA cases; 103 were voriconazole susceptible (79.8%) and 26 were voriconazole resistant (20.2%). All but one resistant case harboured environment-associated resistance mutations in the cyp51A gene: TR34/L98H (13 cases) and TR46/Y121F/T289A (12 cases). Triazole monotherapy was started in 75.0% (97/129) of patients. Mortality at 6 and 12 weeks was higher in voriconazole-resistant cases in all patients (42.3% versus 28.2%, P = 0.20; and 57.7% versus 36.9%, P = 0.064) and in non-ICU patients (36.4% versus 21.6%, P = 0.16; and 54.4% versus 30.7%; P = 0.035), compared with susceptible ones. ICU patient mortality at 6 and 12 weeks was very high regardless of triazole susceptibility (75.0% versus 66.7%, P = 0.99; and 75.0% versus 73.3%, P = 0.99). Conclusions A very high prevalence of voriconazole resistance among culture-positive IA haematology patients was observed. The overall mortality at 12 weeks was significantly higher in non-ICU patients with voriconazole-resistant IA compared with voriconazole-susceptible IA.
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    URL: Article
    DOI: 10.1093/jac/dkz258
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1467478-6
    SSG: 15,3
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  • 3
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    Diagnosing Invasive Pulmonary Aspergillosis in Hematology Patients: a Retrospective Multicenter Evaluation of a Novel Lateral Flow Device
    American Society for Microbiology ; 2019
    In:  Journal of Clinical Microbiology Vol. 57, No. 4 ( 2019-04)
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 57, No. 4 ( 2019-04)
    Abstract: Invasive pulmonary aspergillosis (IPA) is a potentially lethal infection in patients with hematological diseases or following allogeneic stem cell transplantation. Early diagnosis is essential, as delayed treatment results in increased mortality. Recently, a lateral flow device (LFD) for the diagnosis of IPA was CE marked and made commercially available by OLM Diagnostics. We retrospectively analyzed bronchoalveolar lavage fluid (BALf) collected from adult hematology patients from 4 centers in The Netherlands and Belgium. Galactomannan was retested in all samples. All samples were applied to an LFD and read out visually by two independent researchers blinded to the diagnosis of the patient. All samples were also read out using a digital reader. We included 11 patients with proven IPA, 68 patients with probable IPA, 44 patients with possible IPA, and 124 patients with no signs of IPA (controls). In cases of proven IPA versus controls, sensitivity and specificity were 0.82 and 0.86 for visual readout and 0.82 and 0.96 for digital readout, respectively. When comparing patients with proven and probable IPA as cases versus controls, sensitivity and specificity were found to be 0.71 and 0.86, respectively. When excluding serum and BALf galactomannan as mycological criteria from the 2008 European Organization for Research and Treatment of Cancer Invasive Fungal Infections Cooperative Group (EORTC)/Mycoses Study Group of the National Institute of Allergy and Infectious Diseases (MSG) consensus definitions, the LFD was less specific than galactomannan when comparing subjects with proven and probable IPA to controls (0.86 versus 0.96; P = 0.005) but had similar sensitivity (0.76 versus 0.85; P = 0.18). In conclusions, in this large study of the CE-marked LFD in BALf from hematology patients, the LFD had a good performance for the diagnosis of IPA.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.01913-18
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1498353-9
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  • 4
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    Performance of the JF5-Based Galactomannoprotein EIA Compared to the Lateral Flow Device and the Galactomannan EIA in Serum and Bronchoalveolar Lavage Fluid
    American Society for Microbiology ; 2022
    In:  Journal of Clinical Microbiology Vol. 60, No. 11 ( 2022-11-16)
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 60, No. 11 ( 2022-11-16)
    Abstract: Early diagnosis of invasive aspergillosis is an important factor to improve survival but remains challenging. The detection of Aspergillus antigens is included in the consensus case definitions of the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group as a criterion of “probable” invasive aspergillosis. JF5, a mouse IgG3 monoclonal antibody detecting an Aspergillus mannoprotein, has already been implemented as a lateral flow device (LFD). Now, also a JF5-based enzyme-linked immunosorbent assay (EIA) is commercialized ( Aspergillus specific galactomannoprotein [GP] EIA, Euroimmun Medizinische Labordiagnostika AG). In this study, we analyzed the diagnostic performance of GP in 63 bronchoalveolar lavage fluid (BALf) samples and 224 serum samples and compared it to performance of the galactomannan (GM) (Platelia Aspergillus enzyme immunoassay (EIA) (Bio-Rad, Marnes-la-Coquette, France)) and the JF5-based LFD (AspLFD; OLM Diagnostics, Newcastle Upon Tyne, United Kingdom). The diagnostic performance of GP and GM correlated well with both having high specificity. With an optimized cutoff threshold for positivity of 0.4—deviating from the 0.5 threshold recommended by the manufacturer—sensitivity of GP in serum is not significantly different than that of GM. However, in BALf sensitivity of GP is significantly less than for GM.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/jcm.00948-22
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1498353-9
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  • 5
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    A Mortality Prediction Rule for Hematology Patients with Invasive Aspergillosis Based on Serum Galactomannan Kinetics
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 2 ( 2020-02-24), p. 610-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 2 ( 2020-02-24), p. 610-
    Abstract: In invasive aspergillosis (IA), an early and adequate assessment of the response to the initial antifungal therapy remains problematic. We retrospectively analyzed 206 hematology patients with proven or probable IA, and collected serial serum galactomannan (sGM) values and survival status through week 6 and week 12. We created a model for survival at week 6 based on the sGM taken at baseline and on early sGM kinetics. This resulted in a rule predicting that patients with a baseline sGM index 〉 1.4, who failed to lower that index to 〈 0.5 after one week, had a mortality rate of 48.1% at week 6. Conversely, patients presenting with a baseline sGM index ≤1.4 that obtained a negative sGM ( 〈 0.5) after one week, had a mortality that was almost five times lower at only 10.1% by week 6. These findings were confirmed in an external cohort from an independent prospective study. In conclusion, sGM kinetics correlate well with treatment outcomes in hematology patients with IA. We present a rule which is easy to use at the bedside and has good accuracy in predicting week 6 survival.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9020610
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 6
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    Variable Correlation between Bronchoalveolar Lavage Fluid Fungal Load and Serum-(1,3)-β-d-Glucan in Patients with Pneumocystosis—A Multicenter ECMM Excellence Center Study
    MDPI AG ; 2020
    In:  Journal of Fungi Vol. 6, No. 4 ( 2020-12-01), p. 327-
    Details
    In: Journal of Fungi, MDPI AG, Vol. 6, No. 4 ( 2020-12-01), p. 327-
    Abstract: Pneumocystis jirovecii pneumonia is a difficult invasive infection to diagnose. Apart from microscopy of respiratory specimens, two diagnostic tests are increasingly used including real-time quantitative PCR (qPCR) of respiratory specimens, mainly in bronchoalveolar lavage fluids (BAL), and serum β-1,3-d-glucan (BDG). It is still unclear how these two biomarkers can be used and interpreted in various patient populations. Here we analyzed retrospectively and multicentrically the correlation between BAL qPCR and serum BDG in various patient population, including mainly non-HIV patients. It appeared that a good correlation can be obtained in HIV patients and solid organ transplant recipients but no correlation can be observed in patients with hematologic malignancies, solid cancer, and systemic diseases. This observation reinforces recent data suggesting that BDG is not the best marker of PCP in non-HIV patients, with potential false positives due to other IFI or bacterial infections and false-negatives due to low fungal load and low BDG release.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    URL: Article
    DOI: 10.3390/jof6040327
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2784229-0
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  • 7
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    P474 The value of PCR-based azole resistance detection in invasive aspergillosis: A prospective multicenter study
    Oxford University Press (OUP) ; 2022
    In:  Medical Mycology Vol. 60, No. Supplement_1 ( 2022-09-20)
    Details
    In: Medical Mycology, Oxford University Press (OUP), Vol. 60, No. Supplement_1 ( 2022-09-20)
    Abstract:   Objectives Prompt detection of azole-resistant Aspergillus fumigatus will result in the timely start of active treatment and may improve the survival of invasive aspergillosis (IA). The use of a multiplex polymerase chain reaction (PCR) targeting Aspergillus species and fumigatus DNA as well as the two most prevalent azole resistance- associated mutations (RAMs) in the cyp51A gen (TR34/L98H and TR46/Y121F/T289A) could shorten the time to detect azole-resistant IA. Methods In a prospective study in 12 Dutch and Belgian centers, we evaluated the clinical value of the multiplex AsperGenius®PCR in hematology patients with a pulmonary infiltrate undergoing bronchoalveolar lavage (BALf) sampling. The primary endpoint was antifungal treatment failure in the 6 weeks after antifungal treatment initiation in the patients in which azole-resistant IA was detected. Treatment failure was defined as death or a switch to an antifungal agent from another class after at least 5 days of first-line therapy. Patients with a mixed azole-susceptible/resistant infection were excluded from this analysis to ascertain that the infection was indeed caused by the resistant strain. Results Of 323 patients enrolled, sufficient BALf for PCR testing remained in 299. Probable fungal disease was diagnosed in 95 (34%), Aspergillus cultured in 24 (8%), Aspergillus DNA detected in 118 (39%), and A. fumigatus DNA in 88 (29%) patients. The resistance PCR was conclusive in 54/88 (61%) and RAMs were detected in 8 (15%), Table 1. All 8 had probable IA but 2 had a mixed infection and were excluded. In the 6 remaining patients, treatment failure was observed in one. Compared with the GM negative patients and despite antifungal therapy, a positive GM test was associated with a 13% higher 6-week overall mortality (P = .01), Table 2. Surprisingly, the 6-week mortality in the 65 patients who had a positive Aspergillus PCR but a negative GM and culture was not increased compared to those with a negative PCR (PCR + 14% vs. PCR- 16% mortality, P = .68). Conclusions In patients with an underlying hematological disease and a pulmonary infiltrate, the detection of Aspergillus DNA by PCR on BALf was not associated with increased mortality. The exact place of the Aspergillus PCR in the EORTC-MSGERC invasive fungal infection criteria is therefore uncertain. In 15% of the patients in whom A. fumigatus DNA was present, azole RAMs were detected by PCR. In only 1/6 probable cases of IA with RAMs detected, antifungal treatment failure was observed. Basing the choice of antifungal therapy on the result of a cyp51a resistance PCR may help to reduce the impact of azole resistance on mortality.
    Type of Medium: Online Resource
    ISSN: 1369-3786 , 1460-2709
    URL: Article
    DOI: 10.1093/mmy/myac072.P474
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2020733-5
    SSG: 12
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  • 8
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    Implementation of Lateral Flow Assays for the Diagnosis of Invasive Aspergillosis in European Hospitals: A Survey from Belgium and a Literature Review of Test Performances in Different Patient Populations
    Springer Science and Business Media LLC ; 2023
    In:  Mycopathologia Vol. 188, No. 5 ( 2023-10), p. 655-665
    Details
    In: Mycopathologia, Springer Science and Business Media LLC, Vol. 188, No. 5 ( 2023-10), p. 655-665
    Type of Medium: Online Resource
    ISSN: 0301-486X , 1573-0832
    URL: Article
    DOI: 10.1007/s11046-023-00739-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2003647-4
    SSG: 12
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  • 9
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    Point of care aspergillus testing in intensive care patients
    Springer Science and Business Media LLC ; 2020
    In:  Critical Care Vol. 24, No. 1 ( 2020-12)
    Details
    In: Critical Care, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2020-12)
    Abstract: Invasive pulmonary aspergillosis (IPA) is an increasingly recognized complication in intensive care unit (ICU) patients, especially those with influenza, cirrhosis, chronic obstructive pulmonary disease, and other diseases. The diagnosis can be challenging, especially in the ICU, where clinical symptoms as well as imaging are mostly nonspecific. Recently, Aspergillus lateral flow tests were developed to decrease the time to diagnosis of IPA. Several studies have shown promising results in bronchoalveolar lavage fluid (BALf) from hematology patients. We therefore evaluated a new lateral flow test for IPA in ICU patients. Methods Using left-over BALf from adult ICU patients in two university hospitals, we studied the performance of the Aspergillus galactomannan lateral flow assay (LFA) by IMMY (Norman, OK, USA). Patients were classified according to the 2008 EORTC-MSG definitions, the AspICU criteria, and the modified AspICU criteria, which incorporate galactomannan results. These internationally recognized consensus definitions for the diagnosis of IPA incorporate patient characteristics, microbiology and radiology. The LFA was read out visually and with a digital reader by researchers blinded to the final clinical diagnosis and IPA classification. Results We included 178 patients, of which 55 were classified as cases (6 cases of proven and 26 cases of probable IPA according to the EORTC-MSG definitions, and an additional 23 cases according to the modified AspICU criteria). Depending on the definitions used, the sensitivity of the LFA was 0.88–0.94, the specificity was 0.81, and the area under the ROC curve 0.90–0.94, indicating good overall test performance. Conclusions In ICU patients, the LFA performed well on BALf and can be used as a rapid screening test while waiting for other microbiological results.
    Type of Medium: Online Resource
    ISSN: 1364-8535
    URL: Article
    DOI: 10.1186/s13054-020-03367-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2051256-9
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  • 10
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    Genetic Variation in PFKFB3 Impairs Antifungal Immunometabolic Responses and Predisposes to Invasive Pulmonary Aspergillosis
    American Society for Microbiology ; 2021
    In:  mBio Vol. 12, No. 3 ( 2021-06-29)
    Details
    In: mBio, American Society for Microbiology, Vol. 12, No. 3 ( 2021-06-29)
    Abstract: Activation of immune cells in response to fungal infection involves the reprogramming of their cellular metabolism to support antimicrobial effector functions. Although metabolic pathways such as glycolysis are known to represent critical regulatory nodes in antifungal immunity, it remains undetermined whether these are differentially regulated at the interindividual level. In this study, we identify a key role for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the immunometabolic responses to Aspergillus fumigatus . A genetic association study performed in 439 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) and corresponding donors revealed that the donor, but not recipient, rs646564 variant in the PFKFB3 gene increased the risk of invasive pulmonary aspergillosis (IPA) after transplantation. The risk genotype impaired the expression of PFKFB3 by human macrophages in response to fungal infection, which was correlated with a defective activation of glycolysis and the ensuing antifungal effector functions. In patients with IPA, the risk genotype was associated with lower concentrations of cytokines in the bronchoalveolar lavage fluid samples. Collectively, these findings demonstrate the important contribution of genetic variation in PFKFB3 to the risk of IPA in patients undergoing HSCT and support its inclusion in prognostic tools to predict the risk of fungal infection in this clinical setting. IMPORTANCE The fungal pathogen Aspergillus fumigatus can cause severe and life-threatening forms of infection in immunocompromised patients. Activation of glycolysis is essential for innate immune cells to mount effective antifungal responses. In this study, we report the contribution of genetic variation in the key glycolytic activator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) to the risk of invasive pulmonary aspergillosis (IPA) after allogeneic hematopoietic stem cell transplantation. The PFKFB3 genotype associated with increased risk of infection was correlated with an impairment of the antifungal effector functions of macrophages in vitro and in patients with IPA. This work highlights the clinical relevance of genetic variation in PFKFB3 to the risk of IPA and supports its integration in risk stratification and preemptive measures for patients at high risk of IPA.
    Type of Medium: Online Resource
    ISSN: 2150-7511
    URL: Article
    DOI: 10.1128/mBio.00369-21
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 2557172-2
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