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DT Dang, WE Sponsel, J Graybill, H Nevares; Combined Topical and Systemic Posaconazole (SCH-5692) for Treatment of Refractory Fusarium Keratitis and Endophthalmitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):882.
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Purpose: First report of FDA-approved use of topical ocular posaconazole under UTHSCSA IRB P00041 (6/28/98:Modified open-label treatment protocol for the safety and efficacy of SCH 56592 (posaconazole) in the treatment of refractory mycoses). Methods: An emmetropic 42 year-old immunocompetent woman developed a CL-associated deep central corneal ulcer refractory to sustained high-dose antifungal treatment. Cultures yielded Fusarium solani (MIC 24:48 hrs in µg/ml: amphotericin-B 2:2; natamycin 32:32; posaconazole 1:8). A compassionate-use investigative new drug approval for topical ocular application of posaconazole was requested and promptly issued by the FDA, and informed consent was obtained. Posaconazole (SCH-56592), an investigational broad spectrum triazole, provided by Schering Plough Research Corporation, was administered orally 200mg qid, and by topical ocular application 10mg/0.1ml q2hrly. Treatment commenced 5/9/2000. Aqueous tap drawn that day produced resistant Fusarium on subsequent culture. Results: Within the first week of applying bihourly topical posaconazole suspension (100 mg/ml) and 800 mg of the same each day orally, there was significant clearing of the corneal periphery. Keratoplasty was performed on 20/9/2000. Histology revealed innumerable septate branching fungi within the corneal and iris stroma. One week later, the clear anterior chamber revealed a white lens. Diagnostic vitrectomy yielded posaconazole at a concentration of 0.25 µg/ml in the vitreous (and1.2 µg/ml in the plasma) on 26/9/2000 with no growth on culture. Vision improved, with good projection throughout the periphery, and elective phacoemulsification with planned aphakia was performed on 11/1/2001. Branching elements of the Fusarium were histologically confirmed to have penetrated the lens cortex and capsule, but all cultures were negative. Aqueous tap confirmed posaconazole to be present at a level of 0.9 µg/ml, with plasma level of 1.6 µl/ml. At 16 months, on 4/12/01, aphakic correction yielded 20/100 vision, with 360 degree confrontation. Cosmesis and prognosis for eventual lens replacement and visual rehabilitation now appeared very good. Such an outcome is not anticipated with invasive Fusarium endophthalmitis. Conclusion: An eye with amphoteracin- and natamycin-resistant Fusarium solani keratitis, progressing to invasive endophthalmitis, recovered with good ocular function via an apparently rapid response of the Fusarium to systemic and/or topical posaconazole. Ocular penetration of posaconazole was confirmed on separate occasions by aqueous and vitreous assay.
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