scholarly journals Correlation between Triazole Treatment History and Susceptibility in Clinically Isolated Aspergillus fumigatus

2012 ◽  
Vol 56 (9) ◽  
pp. 4870-4875 ◽  
Author(s):  
Masato Tashiro ◽  
Koichi Izumikawa ◽  
Katsuji Hirano ◽  
Shotaro Ide ◽  
Tomo Mihara ◽  
...  

ABSTRACTThis is the first report of a detailed relationship between triazole treatment history and triazole MICs for 154Aspergillus fumigatusclinical isolates. The duration of itraconazole dosage increased as the itraconazole MIC increased, and a positive correlation was observed (r= 0.5700,P< 0.0001). The number of itraconazole-naïve isolates dramatically decreased as the itraconazole MIC increased, particularly for MICs exceeding 2 μg/ml (0.5 μg/ml versus 2 μg/ml,P= 0.03). We also examined the relationship between cumulative itraconazole usage and the MICs of other azoles. A positive correlation existed between itraconazole dosage period and posaconazole MIC (r= 0.5237,P< 0.0001). The number of itraconazole-naïve isolates also decreased as the posaconazole MIC increased, particularly for MICs exceeding 0.5 μg/ml (0.25 μg/ml versus 0.5 μg/ml,P= 0.004). Conversely, the correlation coefficient obtained from the scattergram of itraconazole usage and voriconazole MICs was small (r= −0.2627,P= 0.001). Susceptibility to three triazole agents did not change as the duration of voriconazole exposure changed. In addition, we carried out detailed analysis, including microsatellite genotyping, for isolates obtained from patients infected with azole-resistantA. fumigatus. We confirmed the presence of acquired resistance to itraconazole and posaconazole due to a G54 substitution in thecyp51Agene for a patient with chronic pulmonary aspergillosis after oral itraconazole therapy. We should consider the possible appearance of azole-resistantA. fumigatusif itraconazole is used for extended periods.

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Cristina Jiménez-Ortigosa ◽  
Caroline Moore ◽  
David W. Denning ◽  
David S. Perlin

ABSTRACT We have identified the first case of an fks1 hot spot 1 point mutation causing echinocandin resistance in a clinical Aspergillus fumigatus isolate recovered from a chronic pulmonary aspergillosis patient with an aspergilloma who first failed azole and polyene therapy and subsequently failed micafungin treatment.


2015 ◽  
Vol 116 (9/10) ◽  
pp. 564-577 ◽  
Author(s):  
RISHABH SHRIVASTAVA ◽  
Preeti Mahajan

Purpose – The purpose of this paper is twofold. First, the study aims to investigate the relationship between the altmetric indicators from ResearchGate (RG) and the bibliometric indicators from the Scopus database. Second, the study seeks to examine the relationship amongst the RG altmetric indicators themselves. RG is a rich source of altmetric indicators such as Citations, RGScore, Impact Points, Profile Views, Publication Views, etc. Design/methodology/approach – For establishing whether RG metrics showed the same results as the established sources of metrics, Pearson’s correlation coefficients were calculated between the metrics provided by RG and the metrics obtained from Scopus. Pearson’s correlation coefficients were also calculated for the metrics provided by RG. The data were collected by visiting the profile pages of all the members who had an account in RG under the Department of Physics, Panjab University, Chandigarh (India). Findings – The study showed that most of the RG metrics showed strong positive correlation with the Scopus metrics, except for RGScore (RG) and Citations (Scopus), which showed moderate positive correlation. It was also found that the RG metrics showed moderate to strong positive correlation amongst each other. Research limitations/implications – The limitation of this study is that more and more scientists and researchers may join RG in the future, therefore the data may change. The study focuses on the members who had an account in RG under the Department of Physics, Panjab University, Chandigarh (India). Perhaps further studies can be conducted by increasing the sample size and by taking a different sample size having different characteristics. Originality/value – Being an emerging field, not much has been conducted in the area of altmetrics. Very few studies have been conducted on the reach of academic social networks like RG and their validity as sources of altmetric indicators like RGScore, Impact Points, etc. The findings offer insights to the question whether RG can be used as an alternative to traditional sources of bibliometric indicators, especially with reference to a rapidly developing country such as India.


mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jane T. Jones ◽  
Ko-Wei Liu ◽  
Xi Wang ◽  
Caitlin H. Kowalski ◽  
Brandon S. Ross ◽  
...  

ABSTRACT Aspergillus fumigatus is a filamentous fungus which can cause multiple diseases in humans. Allergic broncho-pulmonary aspergillosis (ABPA) is a disease diagnosed primarily in cystic fibrosis patients caused by a severe allergic response often to long-term A. fumigatus colonization in the lungs. Mice develop an allergic response to repeated inhalation of A. fumigatus spores; however, no strains have been identified that can survive long-term in the mouse lung and cause ABPA-like disease. We characterized A. fumigatus strain W72310, which was isolated from the expectorated sputum of an ABPA patient, by whole-genome sequencing and in vitro and in vivo viability assays in comparison to a common reference strain, CEA10. W72310 was resistant to leukocyte-mediated killing and persisted in the mouse lung longer than CEA10, a phenotype that correlated with greater resistance to oxidative stressors, hydrogen peroxide, and menadione, in vitro. In animals both sensitized and challenged with W72310, conidia, but not hyphae, were viable in the lungs for up to 21 days in association with eosinophilic airway inflammation, airway leakage, serum IgE, and mucus production. W72310-sensitized mice that were recall challenged with conidia had increased inflammation, Th1 and Th2 cytokines, and airway leakage compared to controls. Collectively, our studies demonstrate that a unique strain of A. fumigatus resistant to leukocyte killing can persist in the mouse lung in conidial form and elicit features of ABPA-like disease. IMPORTANCE Allergic broncho-pulmonary aspergillosis (ABPA) patients often present with long-term colonization of Aspergillus fumigatus. Current understanding of ABPA pathogenesis has been complicated by a lack of long-term in vivo fungal persistence models. We have identified a clinical isolate of A. fumigatus, W72310, which persists in the murine lung and causes an ABPA-like disease phenotype. Surprisingly, while viable, W72310 showed little to no growth beyond the conidial stage in the lung. This indicates that it is possible that A. fumigatus can cause allergic disease in the lung without any significant hyphal growth. The identification of this strain of A. fumigatus can be used not only to better understand disease pathogenesis of ABPA and potential antifungal treatments but also to identify features of fungal strains that drive long-term fungal persistence in the lung. Consequently, these observations are a step toward helping resolve the long-standing question of when to utilize antifungal therapies in patients with ABPA and fungal allergic-type diseases.


2020 ◽  
Vol 6 (4) ◽  
pp. 249
Author(s):  
Kauser Jabeen ◽  
Joveria Farooqi ◽  
Nousheen Iqbal ◽  
Khalid Wahab ◽  
Muhammad Irfan

Despite a high burden of chronic pulmonary aspergillosis (CPA) in Pakistan, Aspergillus-specific IgG testing is currently not available. Establishing cut-offs for Aspergillus-specific IgG for CPA diagnosis is crucial due to geographical variation. In settings such as Pakistan, where non-Aspergillus fumigatus (mainly A. flavus) Aspergillus species account for the majority of CPA cases, there is a need to explore additional benefit of Aspergillus flavus-specific IgG detection along with A. fumigatus-specific IgG detection. This study was conducted at the Aga Khan University, Karachi, Pakistan after ethical approval. Serum for IgG detection were collected after informed consent from healthy controls (n = 21), diseased controls (patients with lung diseases, n = 18), and CPA patients (n = 21). A. fumigatus and A. flavus IgG were detected using Siemens immulite assay. The sensitivity and specificity of A. fumigatus-specific IgG were 80.95% and 82.05%, respectively at a cut-off of 20 mg/L. The sensitivity and specificity of A. flavus-specific IgG were 80.95% and 79.49% at a cut-off of 30 mg/L. We report, for the first time, performance of A. flavus-specific IgG for CPA diagnosis. Although there was no statistically significant difference between the performance of both antigens, it seems contextually relevant to include A. flavus IgG in the CPA diagnostic algorithm in regions with higher non-A. fumigatus CPA infections.


Author(s):  
Masato Tashiro ◽  
Takahiro Takazono ◽  
Tomomi Saijo ◽  
Kazuko Yamamoto ◽  
Yoshifumi Imamura ◽  
...  

Abstract Background There are limited data for direct comparisons of the efficacy of oral itraconazole (ITCZ) and oral voriconazole (VRCZ) therapy in the treatment of chronic pulmonary aspergillosis (CPA). Methods We conducted a retrospective, follow-up, observational study of CPA patients enrolled in 2 previous multicenter trials. Results Of the 273 CPA patients, 59 and 101 patients started maintenance therapy with oral ITCZ and oral VRCZ, respectively, just after the end of acute intravenous therapy in each trial. At the end of the observation period in this follow-up study (median observation period, 731 days), the percentage of patients who showed improvement was lower in the ITCZ group than in the VRCZ group (18.2% vs 40.0%). However, after including stable patients, the percentages were 50.9% and 52.6%, respectively, in the ITCZ and VRCZ groups, which were not significantly different (P = .652). Multivariable Cox regression analysis showed no significant influence of the choice of initial maintenance treatment (ITCZ or VRCZ) on overall mortality as well as CPA-associated mortality. Multivariable logistic regression showed that oral ITCZ selection for initial maintenance therapy was an independent risk factor for hospital readmission and switching to other antifungal agents (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3–7.5 and OR, 5.7; 95% CI, 2.0–15.7, respectively). Conclusions Oral VRCZ for initial maintenance therapy showed better effectiveness than oral ITCZ for clinical improvement in CPA patients. There was no difference in crude mortality between initial maintenance therapy with VRCZ and ITCZ, especially in elderly CPA patients.


VINE ◽  
2007 ◽  
Vol 37 (2) ◽  
pp. 150-168 ◽  
Author(s):  
Alex Bennet ◽  
David Bennet

PurposeThis article seeks to introduce the concept of spiritual learning by exploring the value of human characteristics spiritual in nature with respect to their relationship to learning.Design/methodology/approachIn developing this theme, the authors engage a systematic approach: defining terms; identifying representative human characteristics that are spiritual in nature; surfacing assumptions; and identifying emerging themes among the representative spiritual characteristics with respect to learning.FindingsThere appears to be a positive correlation between the representative spiritual characteristics and human learning. For better or worse, the material universe and non‐material universe are married in the conscious and unconscious learning of the human mind.Originality/valueThis work provides a new frame of reference for understanding the relationship between spirituality and learning.


2016 ◽  
Vol 54 (6) ◽  
pp. 1496-1499 ◽  
Author(s):  
Satoru Fujiuchi ◽  
Yuka Fujita ◽  
Hokuto Suzuki ◽  
Kazushi Doushita ◽  
Hikaru Kuroda ◽  
...  

The purpose of this study was to evaluate the clinical utility of a quantitativeAspergillusIgG assay for diagnosing chronic pulmonary aspergillosis. We examinedAspergillus-specific IgG levels in patients who met the following criteria: (i) chronic (duration of >3 months) pulmonary or systemic symptoms, (ii) radiological evidence of a progressive (over months or years) pulmonary lesion with surrounding inflammation, and (iii) no major discernible immunocompromising factors. Anti-AspergillusIgG serum levels were retrospectively analyzed according to defined classifications. MeanAspergillusIgG levels were significantly higher in the proven group than those in the possible and control groups (P< 0.01). Receiver operating characteristic curve analysis revealed that theAspergillusIgG cutoff value for diagnosing proven cases was 50 mg of antigen-specific antibodies/liter (area under the curve, 0.94; sensitivity, 0.98; specificity, 0.84). The sensitivity and specificity for diagnosing proven cases using this cutoff were 0.77 and 0.78, respectively. The positive rates ofAspergillusIgG in the proven and possible groups were 97.9% and 39.2%, respectively, whereas that of the control group was 6.6%. The quantitativeAspergillusIgG assay offers reliable sensitivity and specificity for diagnosing chronic pulmonary aspergillosis and may be an alternative to the conventional precipitin test.


Mycoses ◽  
2018 ◽  
Vol 61 (10) ◽  
pp. 770-776 ◽  
Author(s):  
Inderpaul Singh Sehgal ◽  
Hansraj Choudhary ◽  
Sahajal Dhooria ◽  
Ashutosh Nath Aggarwal ◽  
Mandeep Garg ◽  
...  

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