Purpose: Posaconazole is a triazole antifungal currently in Phase III clinical trials for the treatment and prophylaxis of invasive fungal infections in humans. We describe the use of posaconazole suspension in the treatment of disseminated (meningeal) coccidioidomycosis in a chimpanzee after clinical failure with fluconazole. Clinical Problem: In August 2000, a 4-year-old male chimpanzee with a history of acute lethargy and ascites was diagnosed with systemic coccidioidomycosis. Serum and cerebral spinal fluid (CSF) Coccidioides immitis titers were positive at the time of diagnosis and throughout fluconazole treatment. Despite 6 months of treatment with oral fluconazole, the animal experienced persistent leukocytosis and hypoalbuminemia and his condition worsened. Clinical signs during this time revealed ascites, abdominal masses and peritonitis. In March 2001, the chimpanzee displayed evidence of progressive coccidioidomycosis at which time fluconazole was discontinued. Clinical Approach: Because fluconazole was ineffective and central nervous system involvement was present, oral posaconazole therapy was initiated. Outcome: Within several months of initiation of posaconazole therapy, the chimpanzee demonstrated significant clinical improvement. CSF titers were negative for C. immitis. The animal had gained weight and stature, and had started to regrow hair. Peritoneal masses had significantly diminished, and the ascites and amount of pleural fluid accumulation had also diminished. Over the next several months of posaconazole therapy, steady clinical improvements were observed. Maintenance posaconazole therapy was well tolerated and was not associated with any aberrant side effects such as an abnormal electrocardiogram. The coccidiodomycosis appeared to have been treated effectively based on clinical findings and laboratory tests. The chimpanzee was later euthanized after a severe case of Balantidium coli and further complications associated with immunosuppression. During his episode of diarrhea, he was non-compliant taking the posaconazole and had recurrence of a weak serum Coccidiodes titer within several weeks. Necropsy findings revealed no evidence of C. immitis in tissues. Conclusions: In a chimpanzee with disseminated coccidioidomycosis with meningeal involvement that was refractory to oral fluconazole, oral posaconazole induced negative titers and rapid resolution of symptoms. Recurrence of a serum Coccidiodes titer after discontinuation of posaconazole suggests ongoing treatment may be necessary. Results from clinical trials in humans demonstrate the activity of posaconazole against Coccidioides. Our experience confirms these data and suggests activity of posaconazole in the CNS.
Full conference title:
The 15 th Congress of the International Society for Human and Animal Mycology
- ISHAM 15th (2003)