scholarly journals Tissue Distribution and Penetration of Isavuconazole at the Site of Infection in Experimental Invasive Aspergillosis in Mice with Underlying Chronic Granulomatous Disease

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Annie Lee ◽  
Brendan Prideaux ◽  
Min Hee Lee ◽  
Matthew Zimmerman ◽  
Enriko Dolgov ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Invasive Aspergillosis ◽  
Chronic Granulomatous Disease ◽  
Lung Tissue ◽  
Fungal Pathogens ◽  
High Efficiency ◽  
Wide Spectrum ◽  
Histopathological Analysis ◽  
Ionization Mass ◽  
Granulomatous Disease

ABSTRACTIsavuconazole, the active moiety of the prodrug isavuconazonium sulfate, has potent activity against a wide spectrum of fungal pathogens and is approved for the treatment of invasive aspergillosis, yet little is known about the tissue penetration of isavuconazole at the target sites of infection. Here, we explored the spatial and quantitative distribution of isavuconazole in tissue lesions in experimental pulmonary aspergillosis established in mice with chronic granulomatous disease (CGD) (gp91phox−). Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and laser capture microdissection (LCM)-directed high-pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) were used to analyze infected lungs and brain tissues collected 1, 3, 6, and 24 h after a single oral administration of the prodrug at a dose of 256 mg/kg of body weight (corresponding to 122.9 mg/kg of isavuconazole). Drug enrichment within granulomatous lesions was observed in lung tissue at 1 h postdose, although drug levels quickly equilibrated afterwards between lesion and nonlesion areas. A prominent antifungal effect in the infected lung tissue was revealed by histopathological analysis. Isavuconazole also penetrated into the brain with high efficiency. These data further support the value of isavuconazole to treat patients with invasive aspergillosis.

scholarly journals Back Pain in a 23-Year-Old Male With X-Linked Chronic Granulomatous Disease

2019 ◽  
Vol 6 (11) ◽  
Author(s):  
Michelle C Sabo ◽  
Michela Blain ◽  
Denise McCulloch ◽  
Heather L Glasgow ◽  
Dhruba J Sengupta ◽  
...  
Keyword(s):  
Back Pain ◽  
Invasive Aspergillosis ◽  
Chronic Granulomatous Disease ◽  
Vertebral Osteomyelitis ◽  
Aspergillus Species ◽  
Granulomatous Disease ◽  
First Case ◽  
Increased Risk

Abstract Patients with chronic granulomatous disease are at increased risk for invasive aspergillosis. Cryptic Aspergillus species are being increasingly recognized as distinct causes of infection in this population. In this study, we describe the first case of Aspergillus udagawae vertebral osteomyelitis in a patient with X-linked chronic granulomatous disease.

Low Interleukin-17A Production in Response to Fungal Pathogens in Patients with Chronic Granulomatous Disease

2012 ◽  
Vol 32 (4) ◽  
pp. 159-168 ◽  
Author(s):  
Sanne P. Smeekens ◽  
Stefanie S.V. Henriet ◽  
Mark. S. Gresnigt ◽  
Leo A.B. Joosten ◽  
Peter W.M. Hermans ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Fungal Pathogens ◽  
Granulomatous Disease ◽  
Interleukin 17A

Remote ablation chamber for high efficiency particle transfer in laser ablation electrospray ionization mass spectrometry

The Analyst ◽  
2020 ◽  
Vol 145 (17) ◽  
pp. 5861-5869
Author(s):  
Marjan Dolatmoradi ◽  
Jarod A. Fincher ◽  
Andrew R. Korte ◽  
Nicholas J. Morris ◽  
Akos Vertes
Keyword(s):  
Mass Spectrometry ◽  
Laser Ablation ◽  
Electrospray Ionization ◽  
Electrospray Ionization Mass Spectrometry ◽  
High Efficiency ◽  
Ionization Mass Spectrometry ◽  
Ionization Mass ◽  
Particle Transfer ◽  
Laser Ablation Electrospray Ionization

Improved remote ablation chamber for particle transfer in LAESI mass spectrometry.

Successful Treatment of Invasive Aspergillosis in Chronic Granulomatous Disease by Bone Marrow Transplantation, Granulocyte Colony-Stimulating Factor–Mobilized Granulocytes, and Liposomal Amphotericin-B

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2719-2724 ◽  
Author(s):  
Hülya Ozsahin ◽  
Maya von Planta ◽  
Irene Müller ◽  
Hans C. Steinert ◽  
David Nadal ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Invasive Aspergillosis ◽  
Chronic Granulomatous Disease ◽  
Marrow Transplantation ◽  
Granulomatous Disease ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Aspergillus Infection ◽  
Stimulating Factor

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency with complete absence or malfunction of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the phagocytic cells. Life-threatening infections especially with aspergillus are common despite optimal antimicrobial therapy. Bone marrow transplantation (BMT) is contraindicated during invasive aspergillosis in any disease setting. We report an 8-year-old patient with CGD who underwent HLA-genoidentical BMT during invasive multifocal aspergillus nidulans infection, nonresponsive to treatment with amphotericin-B and γ-interferon. During the first 10 days post-BMT, the patient received granulocyte colony-stimulating factor (G-CSF)–mobilized, 25 Gy irradiated granulocytes from healthy volunteers plus G-CSF beginning on day 3 to prolong the viability of the transfused granulocytes. This was confirmed in vitro by apoptosis assays and in vivo by finding nitroblue tetrazolium (NBT)-positive granulocytes in peripheral blood 12 and 36 hours after the transfusions. Clinical and biological signs of infection began to disappear on day 7 post-BMT. Positron emission tomography with F18-fluorodeoxyglucose (FDG-PET) and computed tomography (CT) scans at 3 months post-BMT showed complete disappearance of infectious foci. At 2 years post-BMT, the patient is well with full immune reconstitution and no sign of aspergillus infection. Our results show that HLA-identical BMT may be successful during invasive, noncontrollable aspergillus infection, provided that supportive therapy is optimal. © 1998 by The American Society of Hematology.

Resistant Invasive Aspergillosis in an Autosomal Recessive Chronic Granulomatous Disease

2012 ◽  
Vol 32 (4) ◽  
pp. 241-245
Author(s):  
Lamia Sfaihi ◽  
Ines Maaloul ◽  
Hela Fourati ◽  
Marie José Stasia ◽  
Zeineb Mnif ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Chronic Granulomatous Disease ◽  
Autosomal Recessive ◽  
Granulomatous Disease

scholarly journals Flucloxacillin Results in Suboptimal Plasma Voriconazole Concentrations

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Eline W. Muilwijk ◽  
Bart G. J. Dekkers ◽  
Stefanie S. V. Henriet ◽  
Paul E. Verweij ◽  
Bregje Witjes ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Pulmonary Aspergillosis ◽  
Gram Positive ◽  
Relevant Interaction

ABSTRACT Combining voriconazole and flucloxacillin is indicated in patient cohorts experiencing both invasive aspergillosis and Gram-positive infections (e.g., patients with chronic granulomatous disease or postinfluenza pulmonary aspergillosis). We report a highly relevant interaction between voriconazole and flucloxacillin, resulting in subtherapeutic plasma voriconazole concentrations in more than 50% of patients, that poses a severe threat if not managed properly.

Failure To Detect Circulating Aspergillus Markers in a Patient with Chronic Granulomatous Disease and Invasive Aspergillosis

2000 ◽  
Vol 38 (10) ◽  
pp. 3900-3901 ◽  
Author(s):  
Paul E. Verweij ◽  
Corry M. Weemaes ◽  
Jo H. A. J. Curfs ◽  
Stephane Bretagne ◽  
Jacques F. G. M. Meis
Keyword(s):  
Invasive Aspergillosis ◽  
Chronic Granulomatous Disease ◽  
Invasive Pulmonary Aspergillosis ◽  
Granulomatous Disease ◽  
Subphrenic Abscess ◽  
Pulmonary Aspergillosis ◽  
Circulating Antigen

We report a patient with chronic granulomatous disease who developed invasive pulmonary aspergillosis and a subphrenic abscess. During treatment, high levels of Aspergillus antigen were detected in the abscess, but circulating antigen andAspergillus DNA were undetectable in the serum.

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