Posaconazole Alone and in Combination with Caspofungin for Treatment of Experimental <i>Exserohilum rostratum</i> Meningoencephalitis: Developing New Strategies for Treatment of Phaeohyphomycosis of the Central Nervous System
Phaeohyphomycosis of the central nervous system (CNS) is a life-threatening infection associated with severe morbidity. New approaches to treatment of CNS phaeohyphomycosis are critically needed. We therefore studied posaconazole with or without caspofungin for treatment of experimental CNS phaeohyp...
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MDPI AG
2020-03-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/6/1/33 |
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| author | Ruta Petraitiene Vidmantas Petraitis BoBo Win Maung Ethan Naing Povilas Kavaliauskas Thomas J. Walsh |
| author_facet | Ruta Petraitiene Vidmantas Petraitis BoBo Win Maung Ethan Naing Povilas Kavaliauskas Thomas J. Walsh |
| author_sort | Ruta Petraitiene |
| collection | DOAJ |
| description | Phaeohyphomycosis of the central nervous system (CNS) is a life-threatening infection associated with severe morbidity. New approaches to treatment of CNS phaeohyphomycosis are critically needed. We therefore studied posaconazole with or without caspofungin for treatment of experimental CNS phaeohyphomycosis caused by <i>Exserohilum rostratum</i>. Each clinical isolate of <i>E. rostratum</i> isolate was inoculated intracisternally with 1.0 × 10<sup>6</sup> microconidia to fully anesthetized New Zealand White rabbits. Profound persistent neutropenia and immunosuppression were established and maintained using cytarabine and methylprednisolone, respectively. Study groups consisted of posaconazole suspension administered as oral formulation at 10 (PSC10) or 20 (PSC20) mg/kg, caspofungin (CFG) at 2 mg/kg intravenously (IV), combinations of PSC10+CFG or PSC20+CFG, and untreated controls (UC). Posaconazole produced a significant reduction of residual fungal burden of <i>E. rostratum</i> in cerebrum, cerebellum, spinal cord, and paravertebral muscle (<i>p</i> < 0.01), in comparison to UC. The combination of PSC10+CFG and PSC20+CFG achieved full clearance of residual fungal burden from cerebrum, while only PSC20+CFG treated rabbits demonstrated clearance from cerebellum, spinal cord, and paravertebral muscle (<i>p</i> < 0.01). These data correlated with the significant reduction of CSF (1→3)-β-<span style="font-variant: small-caps;">d</span>-glucan levels in rabbits treated with PSC20 and PSC20+CFG in comparison to those of UC (<i>p</i> < 0.05). Posaconazole alone or in combination with caspofungin demonstrated significant antifungal efficacy in the treatment of experimental <i>E. rostratum</i> meningoencephalitis and warrants further study for treatment of CNS phaeohyphomycosis. |
| first_indexed | 2024-04-14T00:40:49Z |
| format | Article |
| id | doaj.art-c555836c62704c3e9605a63b773f183b |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-04-14T00:40:49Z |
| publishDate | 2020-03-01 |
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| spelling | doaj.art-c555836c62704c3e9605a63b773f183b2022-12-22T02:22:11ZengMDPI AGJournal of Fungi2309-608X2020-03-01613310.3390/jof6010033jof6010033Posaconazole Alone and in Combination with Caspofungin for Treatment of Experimental <i>Exserohilum rostratum</i> Meningoencephalitis: Developing New Strategies for Treatment of Phaeohyphomycosis of the Central Nervous SystemRuta Petraitiene0Vidmantas Petraitis1BoBo Win Maung2Ethan Naing3Povilas Kavaliauskas4Thomas J. Walsh5Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, NY 10065, USATransplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, NY 10065, USATransplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, NY 10065, USATransplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, NY 10065, USATransplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, NY 10065, USATransplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, NY 10065, USAPhaeohyphomycosis of the central nervous system (CNS) is a life-threatening infection associated with severe morbidity. New approaches to treatment of CNS phaeohyphomycosis are critically needed. We therefore studied posaconazole with or without caspofungin for treatment of experimental CNS phaeohyphomycosis caused by <i>Exserohilum rostratum</i>. Each clinical isolate of <i>E. rostratum</i> isolate was inoculated intracisternally with 1.0 × 10<sup>6</sup> microconidia to fully anesthetized New Zealand White rabbits. Profound persistent neutropenia and immunosuppression were established and maintained using cytarabine and methylprednisolone, respectively. Study groups consisted of posaconazole suspension administered as oral formulation at 10 (PSC10) or 20 (PSC20) mg/kg, caspofungin (CFG) at 2 mg/kg intravenously (IV), combinations of PSC10+CFG or PSC20+CFG, and untreated controls (UC). Posaconazole produced a significant reduction of residual fungal burden of <i>E. rostratum</i> in cerebrum, cerebellum, spinal cord, and paravertebral muscle (<i>p</i> < 0.01), in comparison to UC. The combination of PSC10+CFG and PSC20+CFG achieved full clearance of residual fungal burden from cerebrum, while only PSC20+CFG treated rabbits demonstrated clearance from cerebellum, spinal cord, and paravertebral muscle (<i>p</i> < 0.01). These data correlated with the significant reduction of CSF (1→3)-β-<span style="font-variant: small-caps;">d</span>-glucan levels in rabbits treated with PSC20 and PSC20+CFG in comparison to those of UC (<i>p</i> < 0.05). Posaconazole alone or in combination with caspofungin demonstrated significant antifungal efficacy in the treatment of experimental <i>E. rostratum</i> meningoencephalitis and warrants further study for treatment of CNS phaeohyphomycosis.https://www.mdpi.com/2309-608X/6/1/33experimental <i>exserohilum rostratum</i> meningoencephalitisposaconazole and caspofungin combinationrabbits |
| spellingShingle | Ruta Petraitiene Vidmantas Petraitis BoBo Win Maung Ethan Naing Povilas Kavaliauskas Thomas J. Walsh Posaconazole Alone and in Combination with Caspofungin for Treatment of Experimental <i>Exserohilum rostratum</i> Meningoencephalitis: Developing New Strategies for Treatment of Phaeohyphomycosis of the Central Nervous System Journal of Fungi experimental <i>exserohilum rostratum</i> meningoencephalitis posaconazole and caspofungin combination rabbits |
| title | Posaconazole Alone and in Combination with Caspofungin for Treatment of Experimental <i>Exserohilum rostratum</i> Meningoencephalitis: Developing New Strategies for Treatment of Phaeohyphomycosis of the Central Nervous System |
| title_full | Posaconazole Alone and in Combination with Caspofungin for Treatment of Experimental <i>Exserohilum rostratum</i> Meningoencephalitis: Developing New Strategies for Treatment of Phaeohyphomycosis of the Central Nervous System |
| title_fullStr | Posaconazole Alone and in Combination with Caspofungin for Treatment of Experimental <i>Exserohilum rostratum</i> Meningoencephalitis: Developing New Strategies for Treatment of Phaeohyphomycosis of the Central Nervous System |
| title_full_unstemmed | Posaconazole Alone and in Combination with Caspofungin for Treatment of Experimental <i>Exserohilum rostratum</i> Meningoencephalitis: Developing New Strategies for Treatment of Phaeohyphomycosis of the Central Nervous System |
| title_short | Posaconazole Alone and in Combination with Caspofungin for Treatment of Experimental <i>Exserohilum rostratum</i> Meningoencephalitis: Developing New Strategies for Treatment of Phaeohyphomycosis of the Central Nervous System |
| title_sort | posaconazole alone and in combination with caspofungin for treatment of experimental i exserohilum rostratum i meningoencephalitis developing new strategies for treatment of phaeohyphomycosis of the central nervous system |
| topic | experimental <i>exserohilum rostratum</i> meningoencephalitis posaconazole and caspofungin combination rabbits |
| url | https://www.mdpi.com/2309-608X/6/1/33 |
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