Posaconazole concentrations in the central nervous system

Rüping, Maria J. G. T.; Albermann, Nadine; Ebinger, Friedrich; Burckhardt, Irene; Beisel, Claudia; Müller, Carsten; Vehreschild, Jörg J.; Kochanek, Matthias; Fätkenheuer, Gerd; Bangard, Christopher; Ullmann, Andrew J.; Herr, Wolfgang; Kolbe, Karin; Hallek, Michael; Cornely, Oliver A.

doi:10.1093/jac/dkn409

Cited by 69 publications

(58 citation statements)

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“…Paecilomyces variotii (ATCC 22319), Candida parapsilosis (ATCC 22019), and Candida krusei (ATCC 6258) were used as quality control organisms. Values for MIC 50 and MIC 90 were obtained by ordering the MIC data for each antifungal in ascending arrays and selecting the median and 90th quartile of the MIC distribution, respectively. Geometric mean MICs were computed using the Microsoft Office Excel 2003 SP3 program, for which purpose values less than x were set equal to 0.5x.…”

Section: Fungal Strainsmentioning

confidence: 99%

Use of Amplified Fragment Length Polymorphism To Identify 42 Cladophialophora Strains Related to Cerebral Phaeohyphomycosis with In Vitro Antifungal Susceptibility

et al. 2010

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The amplified fragment length polymorphism technique has been applied to identify neurotropic chaetothyrialean black yeasts and relatives from clinical sources. Cladophialophora bantiana, C. emmonsii, C. arxii, C. devriesii, and C. modesta, previously identified on the basis of sequencing and phenotypic and physiological criteria, were confirmed by cluster analysis, demonstrating the clear separation of C. bantiana as a rather homogeneous group from the other species. C. bantiana is a neurotropic fungus causing cerebral abscesses with a mortality of up to 70%. Successful therapy consists of neurosurgical intervention and optimal antifungal therapy. Since the latter is not clearly defined in a large series, we tested the in vitro activities of eight antifungal drugs against clinical isolates of C. bantiana (n ‫؍‬ 37), C. modesta (n ‫؍‬ 2), C. arxii (n ‫؍‬ 1), C. emmonsii (n ‫؍‬ 1), and C. devriesii (n ‫؍‬ 1), all of which had caused invasive infections. The resulting MIC 90 s for all neurotropic C. bantiana strains were as follows, in increasing order: posaconazole, 0.125 g/ml; itraconazole, 0.125 g/ml; isavuconazole, 0.5 g/ml; amphotericin B, 1 g/ml; voriconazole, 2 g/ml; anidulafungin, 2 g/ml; caspofungin, 4 g/ml; and fluconazole, 64 g/ml. On the basis of these in vitro results and the findings of previous clinical and animal studies, posaconazole seems to be a good alternative to the standard treatment, amphotericin B, for C. bantiana cerebral infections. The new agent isavuconazole, which is also available as an intravenous preparation, has adequate activity against C. bantiana.

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Section: Fungal Strainsmentioning

confidence: 99%

Use of Amplified Fragment Length Polymorphism To Identify 42 Cladophialophora Strains Related to Cerebral Phaeohyphomycosis with In Vitro Antifungal Susceptibility

et al. 2010

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“…In contrast, substantial higher posaconazole CSF concentrations (153-221 ng/ml) with CSF/plasma ratios ranging from 0.4 to 2.3 were recently reported in two patients. 8 Both these patients had CNS infections (one bacterial meningitis with Aspergillus abscess/ventriculitis, one bacterial brain abscess) suggesting that inflammatory disruption of the blood-brain barrier could promote CNS penetration of posaconazole. It is noted that posaconazole CSF concentrations were undetectable (o10 ng/ml) in another patient from this report and this patient had fungal sinusitis without evidence of a CNS infection.…”

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confidence: 96%

“…7 In a recent report, posaconazole CSF concentrations ranged from 153 to 221 ng/ml in two patients and were undetectable in another patient. 8 In October 2007, a 23-year-old male patient with meningeal and systemic relapse of acute myeloid leukemia underwent a second alloHSCT from an unrelated, matched donor using a reduced-intensity conditioning regimen (fludarabine 150 mg/m 2 , melphalan 140 mg/m 2 ). The post transplant period was complicated by an invasive, pulmonary aspergillosis, which was initially treated with caspofungin (70 mg loading dose, followed by 50 mg daily) and subsequently with a combination of caspofungin and voriconazole (day 1: 400 mg b.i.…”

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confidence: 99%

“…It is noted that posaconazole CSF concentrations were undetectable (o10 ng/ml) in another patient from this report and this patient had fungal sinusitis without evidence of a CNS infection. 8 In general, substances may penetrate more easily into the CSF compared with brain tissue, as the blood-CSF barrier mainly consists of a fenestrated epithelium, whereas the epithelium at the blood-brain barrier is connected with tight junctions. 9 Interestingly, reported concentrations of voriconazole in brain tissue exceed those in CSF, indicating brain tissue accumulation.…”

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confidence: 99%

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Limited penetration of posaconazole into cerebrospinal fluid in an allogeneic stem cell recipient with invasive pulmonary aspergillosis

Reinwald

Uharek

Lampe³

et al. 2009

Bone Marrow Transplant

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“…He did not undergo surgical resection of his multiple brain and lung lesions. His brain disease subsequently progressed possibly due to low posaconazole levels which can be associated with poor oral intake due to mucositis (7), reduced central nervous system penetration of posaconazole as suggested in prior reported cases with very low to undetectable posaconazole levels in cerebrospinal fluid (8,9), or antifungal resistance. Ervens and colleagues also found very low levels of posaconazole in plasma and in sampled soft tissue of their patient after 24 days of posaconazole treatment (6).…”

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Isavuconazole Treatment of a Patient with Disseminated Mucormycosis

et al. 2014

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cWe report a patient with relapsed acute myelogenous leukemia after allogeneic stem cell transplantation who developed disseminated mucormycosis due to Rhizomucor pusillus/R. miehei involving lung, brain, and skin. After failing posaconazole and being intolerant to amphotericin, he was treated effectively with isavuconazole for over 6 months despite ongoing treatment for relapsed leukemia. CASE REPORTA 59-year-old male construction worker, with a history of coronary artery disease, was diagnosed with myelodysplastic syndrome (MDS) and underwent reduced-intensity HLAmatched related allogeneic hematopoietic stem cell transplantation (HSCT) in October 2008. In July 2009 (9 months later), a bone marrow biopsy specimen demonstrated MDS relapse and progression to acute myelogenous leukemia (AML), which persisted despite tapering of immunosuppression and donor-lymphocyte infusion.In August 2009, he presented to the emergency room with left upper quadrant and shoulder pain, diaphoresis, and fevers. A chest X-ray demonstrated a left lower lobe infiltrate. He was admitted to the hospital and started on ceftazidime for suspected bacterial pneumonia. His leukocyte count was 36,000/l with 14% blasts and an absolute neutrophil count of 11,500/l. The patient underwent bronchoalveolar lavage, but no bacteria or fungi grew in culture. Serum galactomannan and (1¡3)-␤-D-glucan results were also negative. He was started on hydroxyurea and reinduction chemotherapy with cytarabine and daunorubicin after bone marrow biopsy confirmed progressive AML.His hospital course was complicated by neutropenia, mucositis, persistent fevers, and pain and redness at his central venous catheter site. The catheter was removed and empirical treatment with vancomycin and micafungin was initiated a week after admission.Ten days after admission, a chest computed tomography (CT) scan revealed a left-sided pleural effusion, scattered areas of nodular consolidation with adjacent ground glass in the right lower lobe, and bilateral ground-glass abnormalities. The patient developed altered mental status and facial droop 18 days after admission. A head CT was normal. A subsequent brain magnetic resonance imaging (MRI) procedure demonstrated multiple foci of restricted diffusion compatible with acute ischemia or embolic events.The patient developed violaceus nodular plaques on his face, scalp, posterior neck, and middle and upper back 2 weeks after admission. A skin biopsy was performed and revealed hyphal forms suggestive of mucormycosis within and outside dermal vessels on hematoxylin-eosin stain. Skin biopsy cultures were negative. Three weeks after admission, treatment with liposomal amphotericin (LAmB) (5 mg/kg of body weight) once daily was started. Improvement was noted, with a decrease in the size of the skin lesions and partial improvement in mental status.The patient received treatment with LAmB for 4 weeks. The infecting species was identified as Rhizomucor pusillus/R. miehei by DNA sequencing performed on formalin-fixed, paraffin-embedded skin biopsy...

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Posaconazole concentrations in the central nervous system

Cited by 69 publications

References 4 publications

Use of Amplified Fragment Length Polymorphism To Identify 42 Cladophialophora Strains Related to Cerebral Phaeohyphomycosis with In Vitro Antifungal Susceptibility

Use of Amplified Fragment Length Polymorphism To Identify 42 Cladophialophora Strains Related to Cerebral Phaeohyphomycosis with In Vitro Antifungal Susceptibility

Limited penetration of posaconazole into cerebrospinal fluid in an allogeneic stem cell recipient with invasive pulmonary aspergillosis

Isavuconazole Treatment of a Patient with Disseminated Mucormycosis

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