scholarly journals Efficacy of Ambruticin Analogs in a Murine Model of Invasive Pulmonary Aspergillosis

2006 ◽  
Vol 50 (10) ◽  
pp. 3464-3466 ◽  
Author(s):  
Lisa Y. Chiang ◽  
Daniele E. Ejzykowicz ◽  
Zong-Qiang Tian ◽  
Leonard Katz ◽  
Scott G. Filler
Keyword(s):  
Antifungal Activity ◽  
Mouse Model ◽  
Invasive Aspergillosis ◽  
Murine Model ◽  
Antifungal Agents ◽  
Invasive Pulmonary Aspergillosis ◽  
Vehicle Control ◽  
Pulmonary Aspergillosis

ABSTRACT Ambruticins are a family of polyketides. The antifungal activity of an ambruticin, KOSN-2079, was tested in the mouse model of invasive aspergillosis. KOSN-2079 significantly reduced pulmonary fungal burdens and improved survival over that with the vehicle control. These results support the continued development of ambruticins as antifungal agents.

scholarly journals Novel Inhalational Murine Model of Invasive Pulmonary Aspergillosis

2004 ◽  
Vol 48 (5) ◽  
pp. 1908-1911 ◽  
Author(s):  
Donald C. Sheppard ◽  
Gunter Rieg ◽  
Lisa Y. Chiang ◽  
Scott G. Filler ◽  
John E. Edwards ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Murine Model ◽  
Human Disease ◽  
Invasive Pulmonary Aspergillosis ◽  
Cortisone Acetate ◽  
Pulmonary Aspergillosis ◽  
Aerosol Chamber ◽  
Novel Model

ABSTRACT We developed a novel model of invasive aspergillosis (IA) that recapitulates human disease. Mice were immunosuppressed with cyclophosphamide and cortisone acetate and then infected in an aerosol chamber. This procedure reproducibly delivered 1 × 103 to 3 × 103 conidia to the lungs. Lethal pulmonary IA developed over 2 weeks and was prevented by amphotericin B.

scholarly journals Chitinase Induction Prior to Caspofungin Treatment of Experimental Invasive Aspergillosis in Neutropenic Rats Does Not Enhance Survival

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Jeannine M. Refos ◽  
Alieke G. Vonk ◽  
Marian T. ten Kate ◽  
Henri A. Verbrugh ◽  
Irma A. J. M. Bakker-Woudenberg ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Invasive Aspergillosis ◽  
Invasive Pulmonary Aspergillosis ◽  
Left Lung ◽  
Chitinase Activity ◽  
Pulmonary Aspergillosis ◽  
Content Type ◽  
Acidic Mammalian Chitinase ◽  
Phosphate Buffered Saline

ABSTRACT Host chitinases, chitotriosidase and acidic mammalian chitinase (AMCase), improved the antifungal activity of caspofungin (CAS) against Aspergillus fumigatus in vitro. These chitinases are not constitutively expressed in the lung. Here, we investigated whether chitosan derivatives were able to induce chitinase activity in the lungs of neutropenic rats and, if so, whether these chitinases were able to prolong survival of rats with invasive pulmonary aspergillosis (IPA) or of rats with IPA and treated with CAS. An oligosaccharide-lactate chitosan (OLC) derivative was instilled in the left lung of neutropenic rats to induce chitotriosidase and AMCase activities. Rats instilled with OLC or with phosphate-buffered saline (PBS) were subsequently infected with A. fumigatus and then treated with suboptimal doses of CAS. Survival, histopathology, and galactomannan indexes were determined. Instillation of OLC resulted in chitotriosidase and AMCase activities. However, instillation of OLC did not prolong rat survival when rats were subsequently challenged with A. fumigatus. In 5 of 7 rats instilled with OLC, the fungal foci in the lungs were smaller than those in rats instilled with PBS. Instillation of OLC did not significantly enhance the survival of neutropenic rats challenged with A. fumigatus and treated with a suboptimal dosage of CAS. Chitotriosidase and AMCase activities can be induced with OLC, but the presence of active chitinases in the lung did not prevent the development of IPA or significantly enhance the therapeutic outcome of CAS treatment.

scholarly journals Pretreatment with Empty Liposomes Attenuates the Immunopathology of Invasive Pulmonary Aspergillosis in Corticosteroid-Immunosuppressed Mice

2006 ◽  
Vol 51 (3) ◽  
pp. 1078-1081 ◽  
Author(s):  
Russell E. Lewis ◽  
Georgios Chamilos ◽  
Randall A. Prince ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Body Weight ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis ◽  
Amphotericin B Deoxycholate ◽  
Immunomodulatory Properties ◽  
Immunosuppressed Mice

ABSTRACT In a nonneutropenic murine model of invasive pulmonary aspergillosis, pretreatment with empty liposomes (E-lipo) was nearly as effective as 10 mg/kg of body weight liposomal amphotericin B and superior to 1 mg/kg amphotericin B deoxycholate. The beneficial immunomodulatory properties of E-lipo appear to compensate for their lack of direct antifungal activity.

scholarly journals Assessment of Serum (1→3)-β-d-Glucan Concentration as a Measure of Disease Burden in a Murine Model of Invasive Pulmonary Aspergillosis

2007 ◽  
Vol 52 (3) ◽  
pp. 1176-1178 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Ana C. Vallor ◽  
William R. Kirkpatrick ◽  
Rosie Bocanegra ◽  
...  
Keyword(s):  
Antifungal Therapy ◽  
Murine Model ◽  
Disease Burden ◽  
Antifungal Agents ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis ◽  
Presence And Absence

ABSTRACT Serum (1→3)-β-d-glucan concentrations were serially measured in the presence and absence of antifungal therapy in a murine model of invasive pulmonary aspergillosis. Serum (1→3)-β-d-glucan was detected early during the course of infection, and reductions in this biomarker were associated with improved survival in animals treated with antifungal agents.

scholarly journals Inhaled Voriconazole for Prevention of Invasive Pulmonary Aspergillosis

2009 ◽  
Vol 53 (6) ◽  
pp. 2613-2615 ◽  
Author(s):  
Justin A. Tolman ◽  
Nathan P. Wiederhold ◽  
Jason T. McConville ◽  
Laura K. Najvar ◽  
Rosie Bocanegra ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Murine Model ◽  
Invasive Pulmonary Aspergillosis ◽  
Invasive Disease ◽  
Pulmonary Aspergillosis ◽  
Drug Concentrations ◽  
Intravenous Formulation

ABSTRACT Targeted airway delivery of antifungals as prophylaxis against invasive aspergillosis may lead to high lung drug concentrations while avoiding toxicities associated with systemically administered agents. We evaluated the effectiveness of aerosolizing the intravenous formulation of voriconazole as prophylaxis against invasive pulmonary aspergillosis caused by Aspergillus fumigatus in an established murine model. Inhaled voriconazole significantly improved survival and limited the extent of invasive disease, as assessed by histopathology, compared to control and amphotericin B treatments.

scholarly journals Posaconazole Prophylaxis in Experimental Azole-Resistant Invasive Pulmonary Aspergillosis

2014 ◽  
Vol 59 (3) ◽  
pp. 1487-1494 ◽  
Author(s):  
Seyedmojtaba Seyedmousavi ◽  
Johan W. Mouton ◽  
Willem J. G. Melchers ◽  
Paul E. Verweij
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Murine Model ◽  
Pulmonary Infection ◽  
Invasive Pulmonary Aspergillosis ◽  
Clinical Isolates ◽  
Wild Type ◽  
Breakthrough Infection ◽  
Pulmonary Aspergillosis ◽  
Content Type

ABSTRACTWe investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistantAspergillus fumigatusisolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazole MICs of 0.063 mg/liter (wild type), 0.5 mg/liter (F219I mutation), and 16 mg/liter. A fourth isolate harboring TR34/L98H (MIC of 0.5 mg/liter) was also tested. Posaconazole prophylaxis was effective inA. fumigatuswith posaconazole MICs of ≤0.5 mg/liter, where 100% survival was reached. However, breakthrough infection was observed in mice infected with the isolate for which the posaconazole MIC was >16 mg/liter.

scholarly journals Invasive aspergillosis with disseminated skin ınvolvement in a patient with acute myeloid leukemia: a rare case

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Duygu Mert ◽  
Gülşen Iskender ◽  
Fazilet Duygu ◽  
Alparslan Merdin ◽  
Mehmet Sinan Dal ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Invasive Aspergillosis ◽  
Myeloid Leukemia ◽  
Rare Case ◽  
Invasive Pulmonary Aspergillosis ◽  
Skin Lesions ◽  
Immunocompromised Patients ◽  
Skin Involvement ◽  
Pulmonary Aspergillosis ◽  
Acute Myeloid

Invasive pulmonary aspergillosis is most commonly seen in immunocompromised patients. Besides, skin lesions may also develop due to invasive aspergillosis in those patients. A 49-year-old male patient was diagnosed with acute myeloid leukemia. The patient developed bullous and zosteriform lesions on the skin after the 21st day of hospitalization. The skin biopsy showed hyphae. Disseminated skin aspergillosis was diagnosed to the patient. Voricanazole treatment was initiated. The patient was discharged once the lesions started to disappear.

Risks Of Ventilator-Associated Pneumonia And Invasive Pulmonary Aspergillosis In Patients With Viral Acute Respiratory Distress Syndrome Related or Not To Coronavirus 19 Disease

2020 ◽  
Author(s):  
Keyvan Razazi ◽  
Romain ARRESTIER ◽  
Anne-Fleur Haudebourg ◽  
Brice Benelli ◽  
Guillaume Carteaux ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Invasive Aspergillosis ◽  
Distress Syndrome ◽  
Invasive Pulmonary Aspergillosis ◽  
Resistant Bacteria ◽  
Ventilator Associated Pneumonia ◽  
Retrospective Case ◽  
Pulmonary Aspergillosis

Abstract Background The goal of this study was to assess risk factors of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with SARS-CoV-2 infection.Methods. We conducted a monocenter retrospective study comparing the prevalence of VAP and invasive aspergillosis between patients with COVID-19 related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS).Results. We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 hours. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p<0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS : 58 (64%) vs. 36 (44%), p=0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14-2.52), p<0.01].The prevalence of multi-drug resistant bacteria (MDR) related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p=0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p<0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p=0.003], but there was no difference in Aspergillus colonization.Conclusions. In this retrospective case-control study, we evidenced a higher prevalence of VAP and MDR-VAP in C-ARDS than in NC-ARDS, and a lower risk for invasive aspergillosis in the former group.

scholarly journals 1346. The Tetrazole VT-1598 Is Efficacious in a Murine Model of Invasive Aspergillosis with a PK/PD Expected of a Mold-Active CYP51 Inhibitor

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S411-S412
Author(s):  
Edward P Garvey ◽  
Andrew Sharp ◽  
Peter Warn ◽  
Christopher M Yates ◽  
Robert J Schotzinger
Keyword(s):  
Antifungal Activity ◽  
Invasive Aspergillosis ◽  
Murine Model ◽  
Pathogenic Fungi ◽  
Rational Drug Design ◽  
Fungal Burden ◽  
Delayed Treatment ◽  
Rational Drug

Abstract Background VT-1598 is a novel fungal CYP51 inhibitor with potent in vitro activity against yeast, mold, and endemic pathogenic fungi (Wiederhold, JAC, 2017). Its tetrazole-based rational drug design imparts much greater selectivity vs. human CYPs (Yates, BMCL, 2017), which could reduce human CYP-related side effects and DDIs. We report here VT-1598’s in vivo activity in an invasive aspergillosis (IA) model. Methods MIC was determined as outlined in CLSI M38-A2. Plasma PK was measured after 4 days of oral doses in neutropenic ICR mice without fungal inoculation. In vivo antifungal activity was determined in a tail-vein IA model in neutropenic mice inoculated with A. fumigatus (AF) ATCC 204305 (N = 10 per dose). Two separate studies were conducted, with oral VT-1598 treatment starting either 48 hours prior (prophylaxis) or 5 hours postinoculation (delayed), with 4 days of postinoculation dosing, and kidney fungal burden measured 1 day post last dose by both CFU and qPCR. Drug control was 10 mg/kg AmBisome i.v. Results The MIC for VT-1598 against AF 204305 was 0.25 μg/mL. The plasma PK of VT-1598 was linearly proportional between the 5 and 40 mg/kg once-daily doses, with AUCs of 155 and 1,033 μg h/mL for the two doses, respectively. VT-1598 was similarly effective in reducing fungal burden when given in delayed treatment compared with prophylaxis, and both studies demonstrated a full dose–response (i.e., no to full reduction of fungal burden). When comparing fungal burdens of each dose group to the fungal burden at the start of treatment, the dose of VT-1598 to achieve fungal stasis ranged from 20.5 to 25.9 mg/kg and to achieve a 1-log10 fungal kill ranged from 30.9 to 50.5 mg/kg. Using the previously measured mouse plasma binding (&gt;99.9%), the free AUC /MIC values for stasis and 1-log10 kill ranged from 2.1–2.7 and 3.2–5.2, respectively. These values are within the range of 1–11 that have been reported for posaconazole and isavuconazole (Lepak, AAC, 2013). Conclusion VT-1598 had potent antifungal activity in a murine model of IA. The PK/PD relationship was the same as clinically used mold-active CYP51 agents, suggesting that it could have similar clinical efficacy. If correct, the tetrazole-based greater selectivity may significantly differentiate VT-1598 from current IA therapies. Disclosures E. P. Garvey, Viamet Pharmaceuticals, Inc.: Employee, Salary. A. Sharp, Evotec (UK) Ltd.: Employee, Salary. P. Warn, Evotec (UK) Ltd.: Employee, Salary. C. M. Yates, Viamet Pharmaceuticals, Inc.: Employee, Salary. R. J. Schotzinger, Viamet Pharmaceuticals, Inc.: Board Member and Employee, Salary.

scholarly journals Efficacy of Nebulized Liposomal Amphotericin B in Treatment of Experimental Pulmonary Aspergillosis

2005 ◽  
Vol 49 (7) ◽  
pp. 3028-3030 ◽  
Author(s):  
Joan Gavaldà ◽  
María-Teresa Martín ◽  
Pedro López ◽  
Xavier Gomis ◽  
José-Luís Ramírez ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Liposomal Amphotericin B ◽  
Pulmonary Aspergillosis ◽  
Lower Lung

ABSTRACT The efficacy of therapeutic aerosolized amphotericin B (AMB) was studied in a steroid-immunosuppressed murine model of invasive pulmonary aspergillosis. Nebulized liposomal AMB can be a valid approach to the treatment of this infection, with subjects showing significantly improved survival relative to that of subjects given intravenous deoxycholate AMB, as well as lower lung weights and pulmonary glucosamine levels.

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