P7 Efficacy of antifungal therapy with inhaled azole against murine invasive pulmonary aspergillosis with ITCZ-low susceptible Aspergillus fumigatus

2013 ◽  
Vol 42 ◽  
pp. S43
Author(s):  
K. Hirano ◽  
K. Izumikawa ◽  
Y. Morinaga ◽  
S. Kurihara ◽  
S. Nakamura ◽  
...  
2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S613-S613
Author(s):  
Hayato Mitaka ◽  
David C Perlman ◽  
Waleed Javaid ◽  
Nadim Salomon

Abstract Background Invasive pulmonary aspergillosis (IPA) has been reported in critically ill patients without pre-existing immunocompromising conditions. However, there are scant data on pulmonary aspergillosis in patients with COVID-19. Methods We performed a retrospective review of pharmacy records of antifungal use during 3/21-4/22, 2020, and collect longitudinal clinical data. Cases were then classified by the clinical algorithm for IPA in the ICU (AspICU). Results 7 out of 18 (39%) patients who received antifungal therapy had Aspergillus fumigatus in tracheal aspirate specimens while mechanically ventilated in the ICU. None of the patients had EORTC/MSG host factors. Median time from admission to the date of positive respiratory culture was 9 days (range: 2-15). High-dose glucocorticoids were started a mean of 5.6 days (range 3-8) before the positive respiratory culture in 5 and on the day of the culture in 2. Six received 583-1000 mg equivalent of prednisone. Two received Tocilizumab. By AspICU criteria, 4 had putative IPA. Radiographic abnormalities included cavitary pneumonia, opacities with dense consolidation, worsening infiltrates, and diffuse interstitial and patchy hazy opacities. Compatible signs included worsening respiratory failure in 3 and fever after 3 days of antibacterial agents in 1. Associated findings were leukocytosis in 4, > 1 positive cultures in 3, high procalcitonin in 2, and positive serum galactomannan in 1. The remaining three were classified as colonization as they lacked compatible signs. One had concomitant Klebsiella aerogenes pneumonia with bacteremia, and two later developed Candidemia and Stenotrophomonas maltophilia pneumonia, respectively. All 3 had fever with leukocytosis. One had elevated procalcitonin. Six received antifungal therapy; one did not due to goals of care. All 7 patients expired despite ICU care. Conclusion The critically ill patients with severe COVID-19 in whom respiratory culture grew Aspergillus fumigatus showed very high mortality despite antifungal treatment. By AspICU algorithm, 4 patients had putative IPA. Further data on risk factors and clinical predictors of IPA in COVID-19 are needed. Disclosures All Authors: No reported disclosures


2008 ◽  
Vol 9 (1) ◽  
pp. 99-104 ◽  
Author(s):  
Mehmet Fatih Can ◽  
Gokhan Yagci ◽  
Levent Gorenek ◽  
Ergun Tozkoparan ◽  
Ismail Ozerhan ◽  
...  

2021 ◽  
Vol 14 (7) ◽  
pp. e236887
Author(s):  
Menaka Mahendran ◽  
Daniel Urbine

A 47-year-old Caucasian man on long-standing antifungal therapy for chronic necrotising aspergillosis and a history of recurrent pseudomonas pneumonias presented to the outpatient pulmonary clinic with dyspnoea and chest discomfort for 3 days. A CT angiography of the chest demonstrated angioinvasion from the previously noted left upper lobe cavitary lesion into the left main pulmonary artery, along with new consolidating lesions. Due to the high risk for massive haemoptysis, he was evaluated by thoracic surgery and underwent a successful left pneumonectomy. As invasive pulmonary aspergillosis is associated with high mortality, surgical intervention should always be considered, especially in those who develop extensive disease, despite being on aggressive antifungal therapy. Though minimally described in literature, invasive pulmonary pseudomonas also carries a high mortality risk. In our patient, cultures from the resected lung only demonstrated Pseudomonas aeruginosa.


2012 ◽  
Vol 2012 (dec14 1) ◽  
pp. bcr2012007824-bcr2012007824 ◽  
Author(s):  
S. Abdulaziz ◽  
H. Al Jahdali ◽  
S. Baharoon

2015 ◽  
Vol 47 (1) ◽  
pp. 45-68 ◽  
Author(s):  
David W. Denning ◽  
Jacques Cadranel ◽  
Catherine Beigelman-Aubry ◽  
Florence Ader ◽  
Arunaloke Chakrabarti ◽  
...  

Chronic pulmonary aspergillosis (CPA) is an uncommon and problematic pulmonary disease, complicating many other respiratory disorders, thought to affect ∼240 000 people in Europe. The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), which untreated may progress to chronic fibrosing pulmonary aspergillosis. Less common manifestations include:Aspergillusnodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patients, which should be managed as invasive aspergillosis. Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence ofAspergillusinfection (microscopy or culture from biopsy) or an immunological response toAspergillusspp. and exclusion of alternative diagnoses, all present for at least 3 months.Aspergillusantibody (precipitins) is elevated in over 90% of patients. Surgical excision of simple aspergilloma is recommended, if technically possible, and preferablyviavideo-assisted thoracic surgery technique. Long-term oral antifungal therapy is recommended for CCPA to improve overall health status and respiratory symptoms, arrest haemoptysis and prevent progression. Careful monitoring of azole serum concentrations, drug interactions and possible toxicities is recommended. Haemoptysis may be controlled with tranexamic acid and bronchial artery embolisation, rarely surgical resection, and may be a sign of therapeutic failure and/or antifungal resistance. Patients with singleAspergillusnodules only need antifungal therapy if not fully resected, but if multiple they may benefit from antifungal treatment, and require careful follow-up.


Medicine ◽  
2017 ◽  
Vol 96 (51) ◽  
pp. e9436 ◽  
Author(s):  
Yake Yao ◽  
Hua Zhou ◽  
Yihong Shen ◽  
Qing Yang ◽  
Jian Ye ◽  
...  

Author(s):  
Elena Campione ◽  
Roberta Gaziano ◽  
Elena Doldo ◽  
Daniele Marino ◽  
Mattia Falconi ◽  
...  

AIM: Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. Fungistatic activity of all-trans retinoic acid (ATRA) has been recently described in vitro. We evaluated the efficacy of ATRA in vivo and its potential synergistic interaction with other antifungal drugs. MATERIALS AND METHODS: A rat model of IPA and in vitro experiments were performed to assess the efficacy of ATRA against Aspergillus in association with classical antifungal drugs and in silico studies used to clarify its mechanism of action. RESULTS: ATRA (0.5 and 1 mM) displayed a strong fungistatic activity in Aspergillus cultures, while at lower concentrations, synergistically potentiated fungistatic efficacy of sub-inhibitory concentration of Amphotericin B (AmB) and Posaconazole (POS). ATRA also enhanced macrophagic phagocytosis of conidia. In a rat model of IPA, ATRA reduced mortality similarly to Posaconazole. CONCLUSION: Fungistatic efficacy of ATRA alone and synergistically with other antifungal drugs was documented in vitro, likely by inhibiting fungal Hsp90 expression and Hsp90-related genes. ATRA reduced mortality in a model of IPA in vivo. Those findings suggest ATRA as suitable fungistatic agent, also to reduce dosage and adverse reaction of classical antifungal drugs, and new therapeutic strategies against IPA and systemic fungal infections.


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