Date: 26 November 2013
T1 weighted, gadolinium enhanced magnetic resonance brain scan. This 43 year-old alcoholic woman underwent laparoscopic cholecystectomy in January 2001. Ten days after surgery, she became confused, dysphasic and eventually had tonic-clonic seizures. A CT scan showed non-communicating hydrocephalus with ventriculitis. She underwent many complicated neurosurgical interventions, and received long term broad-spectrum antimicrobials and dexamethasone. One month later, she had generalized seizures, and a large abscess was observed on scan (see images). A heavy growth of A. fumigatus was retrieved from the abscess, and amphotericin B and 5-flucytosine were started. Antifungal therapy was changed voriconazole due to intolerance to amphotericin B and worsening disorientation. Voriconazole dosing (which varied from 300mg to 100mg twice daily) was guided by plasma concentrations as enzyme induction with rifampicin and carbamazepine, and reduction in clearance with alcoholic liver disease complicated her voriconazole dosing. Steroids were gradually reduced. She had a good recovery and completed 9 months of voriconazole.
Despite air filtration in the operating rooms, she apparently acquired an intra-operative infection, probably accelerated in presentation by concurrent dexamethasone. Rapid diagnosis and optimization of voriconazole dosing lead to a good outcome.
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Patient with chronic productive cough, chest pain and ABPA, unable to take itraconazole or nebulised amphotericin B. Smokes at least 40 roll up cigarettes a day.
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Laryngeal aspergillosis, probably related to inhaled corticosteroids.
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VL-2397 (formerly known as ASP2397) is a novel antifungal drug initially developed by our partner, Astellas Pharma. This drug was isolated from a leaf litter fungus Acremonium species collected in a Malaysian national park. Astellas presented two posters at the 2014 ICAAC meeting which described the in vitro and the in vivo antifungal activities of this drug. The differentiating attributes from the preclinical data of VL-2397 include:
- A novel mechanism of action, with a potential to be complementary or synergistic with the existing classes of antifungals.
- Rapid fungal cell kill activity demonstrated in preclinical models, which was faster than marketed antifungals.
- Activity against azole-resistant fungal species.
- Low propensity for P450 drug-drug interactions.
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SCY-078, new orally available beta-1,3-d-glucan synthase inhibitor, Formely MK-3118.
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Pt DSM Community acquired primary Aspergillus pneumonia. Two x-rays taken on 02/02/2010 then 05/03/2010
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