scholarly journals Emergence of Azole-Resistant Aspergillus fumigatus from Immunocompromised Hosts in India

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Yubhisha Dabas ◽  
Immaculata Xess ◽  
Sameer Bakshi ◽  
Manoranjan Mahapatra ◽  
Rachna Seth
Keyword(s):  
Prospective Study ◽  
Aspergillus Fumigatus ◽  
Hot Spots ◽  
Patient Population ◽  
Indian Patient ◽  
First Line ◽  
Content Type ◽  
Continued Use ◽  
Immunocompromised Hosts ◽  
Low Rate

ABSTRACT This prospective study shows that the rate of azole-resistant Aspergillus fumigatus (ARAF) in an immunocompromised Indian patient population with invasive aspergillosis (IA) is low, 6/706 (0.8%). This low rate supports the continued use of voriconazole as the first line of treatment. However, the ARAF isolates from India in this study exhibited three kinds of unreported cyp51A mutations, of which two were at hot spots, G54R and P216L, while one was at codon Y431C.

scholarly journals In VitroSusceptibility of Aspergillus fumigatus to Isavuconazole: Correlation with Itraconazole, Voriconazole, and Posaconazole

2013 ◽  
Vol 57 (11) ◽  
pp. 5778-5780 ◽  
Author(s):  
Lea Gregson ◽  
Joanne Goodwin ◽  
Adam Johnson ◽  
Laura McEntee ◽  
Caroline B. Moore ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Azole Resistance ◽  
First Line ◽  
Content Type

ABSTRACTTriazoles are first-line agents for treating aspergillosis. The prevalence of azole resistance inAspergillus fumigatusis increasing, and cross-resistance is a growing concern. In this study, the susceptibilities of 40A. fumigatusclinical isolates were tested by using the CLSI method with amphotericin B, itraconazole, voriconazole, posaconazole, and the new triazole isavuconazole. Isavuconazole MICs were higher in strains with reduced susceptibilities to other triazoles, mirroring changes in voriconazole susceptibility. Isavuconazole MICs differed depending on the Cyp51A substitution.

scholarly journals Dynamics of Aspergillus fumigatus in Azole Fungicide-Containing Plant Waste in the Netherlands (2016–2017)

2020 ◽  
Vol 87 (2) ◽  
Author(s):  
Jianhua Zhang ◽  
Lidia Lopez Jimenez ◽  
Eveline Snelders ◽  
Alfons J. M. Debets ◽  
Anton G. Rietveld ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Hot Spots ◽  
Crop Protection ◽  
Sampling Period ◽  
Resistance Mechanisms ◽  
Content Type ◽  
Long Term Storage ◽  
Fungicide Residues ◽  
Plant Waste

ABSTRACT The treatment of patients suffering from Aspergillus diseases is hampered due to infections with Aspergillus fumigatus that are already resistant to medical azoles. Previous work has suggested that A. fumigatus likely gains resistance through environmental azole exposure in so-called hot spots. Here, we investigated A. fumigatus resistance dynamics over time at three sites at which farmers used azole fungicides for crop protection. Over 16 months, 114 samples were taken from stockpiles of decaying plant waste. A. fumigatus and azole fungicide residues were ubiquitously present in the plant waste. On average, 105 A. fumigatus CFU/g was recovered, of which roughly half were itraconazole and tebuconazole resistant. Similar tandem repeat-mediated resistance mechanisms were found in colonies cultured from plant waste as reported in clinical azole-resistant isolates. Our results show a consistent high burden of azole-resistant A. fumigatus in azole-containing plant waste and underscores the need to further investigate resistance-reducing interventions and transmission routes. IMPORTANCE Aspergillus fumigatus is consistently present independently on season at a high abundance in plant waste material throughout the sampling period. Our study confirmed that long-term storage sites of azole-containing decaying plant material can indeed be considered hot spots, which can sustain resistance development and maintenance in A. fumigatus. Roughly half of individual isolates were azole resistant and carried genetic mutations that are highly similar to those found in patients with azole-resistant invasive aspergillosis. Our work suggests that environmental sources of azole resistance in A. fumigatus may be important, underscoring the need for further studies on environment-to-patient transmission routes.

scholarly journals Signaling Pathways Governing the Caspofungin Paradoxical Effect in Aspergillus fumigatus

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Nicolas Papon ◽  
Florent Morio ◽  
Dominique Sanglard
Keyword(s):  
Aspergillus Fumigatus ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Paradoxical Effect ◽  
Regulatory Pathway ◽  
First Line ◽  
Content Type ◽  
Wide Range ◽  
First Line Treatment

ABSTRACT Aspergillus fumigatus is responsible for a wide range of diseases affecting several million people worldwide. Currently, a few families of antifungals are available to fight aspergillosis, and we are facing a worrisome increase in resistance to azoles, the drugs used for both first-line treatment and prophylaxis of invasive aspergillosis. In this context, some of the latest antifungals, i.e., echinocandins, have gained attention. Even though acquired resistance to echinocandins is yet uncommon in A. fumigatus clinical isolates, some strains exhibit another characteristic that relies on their capacity to grow at suprainhibitory echinocandin concentrations in vitro. This intriguing phenomenon, especially observed with caspofungin and now referred to as the caspofungin paradoxical effect (CPE), relies on molecular mechanisms that were hitherto little understood. Here, we discuss the recent key findings of Valero and colleagues published in mBio (C. Valero, A. C. Colabardini, J. Chiaratto, L. Pardeshi, et al., mBio 11:e00816-20, 2020, https://doi.org/10.1128/mBio.00816-20) that will allow a better understanding of the complex regulatory pathway involved in governing the response of A. fumigatus to caspofungin.

scholarly journals Genomic Diversity of Azole-Resistant Aspergillus fumigatus in the United States

mBio ◽  
2021 ◽  
Author(s):  
Kizee A. Etienne ◽  
Elizabeth L. Berkow ◽  
Lalitha Gade ◽  
Natalie Nunnally ◽  
Shawn R. Lockhart ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
The United States ◽  
Genomic Diversity ◽  
First Line ◽  
Content Type ◽  
Severe Influenza ◽  
Common Causes ◽  
Immune Deficiencies ◽  
Line Of Therapy ◽  
Invasive Mold Infections

Aspergillus fumigatus is one of the most common causes of invasive mold infections in patients with immune deficiencies and has also been reported in patients with severe influenza and severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2). Triazole drugs are the first line of therapy for this infection; however, their efficacy has been compromised by the emergence of azole resistance in A. fumigatus , which was proposed to be selected for by exposure to azole fungicides in the environment [P.

Dynamic Proximal Ulnar Osteotomy for the Treatment of Ununited Anconeal Process in 17 Dogs

1998 ◽  
Vol 11 (02) ◽  
pp. 76-79 ◽  
Author(s):  
B. M. Turner ◽  
R. H. Abercromby ◽  
J. Innes ◽  
W. M. McKee ◽  
M. G. Ness
Keyword(s):  
Clinical Outcome ◽  
Prospective Study ◽  
Patient Population ◽  
Clinical Results ◽  
Radiographic Evaluation ◽  
Proximal Ulna ◽  
Ulnar Osteotomy ◽  
A Prospective Study

SummaryA prospective study was made of 17 dogs with ununited anconeal process treated by osteotomy of the proximal ulna. The effect of the surgery on lameness was evaluated subjectively and the elbows were assessed radiographically for evidence of anconeal fusion and healing of the osteotomy. Whilst clinical outcome was generally good and complications infrequent, relatively few cases achieved anconeal fusion. These results do not compare well with the results of a previous study but this disparity may be due in part to differences in patient population and radiographic evaluation.Further work is required to establish how best to achieve predictable anconeal fusion.Proximal ulnar osteotomy was used to treat 17 dogs with ununited anconeal process. Clinical results were good but anconeal fusion was not achieved consistently. Further work is needed to determine how best to achieve predictable anconeal fusion.

The Effect of Changes in Dialysate Volume on Glucose and Urea Equilibration

1994 ◽  
Vol 14 (3) ◽  
pp. 236-239 ◽  
Author(s):  
Edward C. Kohaut ◽  
F. Bryson Waldo ◽  
Mark R. Benfield
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Prospective Study ◽  
Body Surface ◽  
Patient Population ◽  
Different Ages ◽  
Student’S T ◽  
A Prospective Study ◽  
Dialysate Volume ◽  
Student’S T Test

Objectives To determine the effect of changing dialysate volume on urea and glucoseequilibration curves and to determine, if dialysate volume is prescribed on the basis of body surface area, whether equilibration curves will be consistent in patients of different sizes and ages. Design A prospective study wherein children with acute or chronic renal failure had peritoneal equilibration studies done with dwell volumes of 30 mL/kg, 40 mL/kg, and 1200 mL/m2. Patient Population Twenty-two children: 7 under 3 years of age; 8 between 3 and 10 years of age; 7 older than 10 years of age. Statistics Student's t-test. Results Urea and glucose equilibrated rapidly at dwell volumes of 30 mL/kg, slower at dwell volumes of 40 mL/kg, and slowest at dwell volumes of 1200 mL/m2. Equilibration curves were similar in children of different ages when dialysate volumes of 1200 mL/m2 were infused. Conclusion Dialysate volumes of 1200 mL/m2 should be used when equilibration studies are being done to compare individuals of different ages and sizes.

scholarly journals Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Effective Dose ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Drugs ◽  
Extracellular Matrices ◽  
Content Type ◽  
Order Of Magnitude ◽  
Life Threatening

ABSTRACT Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus cause life-threatening candidiasis, cryptococcosis, and aspergillosis, resulting in several hundred thousand deaths annually. The patients at the greatest risk of developing these life-threatening invasive fungal infections have weakened immune systems. The vulnerable population is increasing due to rising numbers of immunocompromised individuals as a result of HIV infection or immunosuppressed individuals receiving anticancer therapies and/or stem cell or organ transplants. While patients are treated with antifungals such as amphotericin B, all antifungals have serious limitations due to lack of sufficient fungicidal effect and/or host toxicity. Even with treatment, 1-year survival rates are low. We explored methods of increasing drug effectiveness by designing fungicide-loaded liposomes specifically targeted to fungal cells. Most pathogenic fungi are encased in cell walls and exopolysaccharide matrices rich in mannans. Dectin-2 is a mammalian innate immune membrane receptor that binds as a dimer to mannans and signals fungal infection. We coated amphotericin-loaded liposomes with monomers of Dectin-2’s mannan-binding domain, sDectin-2. sDectin monomers were free to float in the lipid membrane and form dimers that bind mannan substrates. sDectin-2-coated liposomes bound orders of magnitude more efficiently to the extracellular matrices of several developmental stages of C. albicans, C. neoformans, and A. fumigatus than untargeted control liposomes. Dectin-2-coated amphotericin B-loaded liposomes reduced the growth and viability of all three species more than an order of magnitude more efficiently than untargeted control liposomes and dramatically decreased the effective dose. Future efforts focus on examining pan-antifungal targeted liposomal drugs in animal models of fungal diseases. IMPORTANCE Invasive fungal diseases caused by Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus have mortality rates ranging from 10 to 95%. Individual patient costs may exceed $100,000 in the United States. All antifungals in current use have serious limitations due to host toxicity and/or insufficient fungal cell killing that results in recurrent infections. Few new antifungal drugs have been introduced in the last 2 decades. Hence, there is a critical need for improved antifungal therapeutics. By targeting antifungal-loaded liposomes to α-mannans in the extracellular matrices secreted by these fungi, we dramatically reduced the effective dose of drug. Dectin-2-coated liposomes loaded with amphotericin B bound 50- to 150-fold more strongly to C. albicans, C. neoformans, and A. fumigatus than untargeted liposomes and killed these fungi more than an order of magnitude more efficiently. Targeting drug-loaded liposomes specifically to fungal cells has the potential to greatly enhance the efficacy of most antifungal drugs.

scholarly journals Understanding consumer loyalty to technology-based self-services with credence qualities

2015 ◽  
Vol 29 (6/7) ◽  
pp. 522-532 ◽  
Author(s):  
Lisa Schuster ◽  
Judy Proudfoot ◽  
Judy Drennan
Keyword(s):  
Professional Services ◽  
Content Type ◽  
Consumer Responses ◽  
Factors Affecting ◽  
Behavioral Loyalty ◽  
Behavioral Domain ◽  
Continued Use ◽  
Self Service ◽  
The Impact ◽  
Goal Directed Behavior

Purpose – This paper aims to use the Model of Goal-Directed Behavior (MGB) to examine the factors affecting consumers’ continued use of emerging technology-based self-services (TBSSs) with credence qualities. Professional services, which traditionally require specialized knowledge and high levels of interpersonal interaction to produce owing to their credence qualities, are increasingly delivered via self-service technologies. Health services delivered via mobile devices, for example, facilitate self-care without direct involvement from health professionals. Design/methodology/approach – A mental health service delivered via the Internet and mobile phone, myCompass, was selected as the research context. Twenty interviews were conducted with users of myCompass and the data were thematically analyzed. Findings – The findings of the study showcase the unique determinants of consumers’ continued use of TBSSs with credence qualities relative to the more routine services which have been the focus of extant research. The findings further provide support for the utility of the MGB in explaining service continuance, although the importance of distinguishing between extrinsic and intrinsic motivational components of behavioral desire and capturing the impact of social influence beyond subjective norms is also highlighted. Originality/value – This study contributes to recent research examining differences in consumer responses across TBSSs and behavioral loyalty to these services. It also provides empirical evidence for broadening and deepening the MGB within this behavioral domain.

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