Objective: Histoplasmosis is endemic in the Western Hemisphere. However, current therapy limitations include poor absorption, dose-limiting toxicities and poor long-term tolerability. Posaconazole (POS), a new triazole, has demonstrated activity in an animal model of histoplasmosis. This abstract reports the use of POS in 7 patients as salvage treatment of histoplasmosis after standard antifungal therapies failed. Methods: All patients enrolled in this open-label trial were intolerant of, or had proven or probable histoplasmosis that was refractory to amphotericin B (AMB), fluconazole (FLZ), itraconazole (ITZ), or voriconazole (VORI). POS 800 mg/day was administered orally as either 200 mg QID or 400 mg BID. Maximum duration of dosing in these patients was 34 weeks. Success was defined as complete or partial clinical response with microbiological eradication; stable disease was considered a failure. Results: In 6 of 7 cases (86%), POS therapy resulted in significant clinical improvements (table). In several cases, clinical improvement was seen after 1 month of treatment with POS after these patients were treated with >24 weeks of other antifungal therapy. Case Patient Demographics Site of Infection Outcome Duration of POS Treatment (Patient #) (Underlying Disease) (days) 1 M, 79 Adrenal gland Failure 168 2 M, 81, (aplastic anemia) Disseminated Success 41 3 M, 35, (HIV) Disseminated Success 161 4 M, 57 CNS Success 241 5 F, 29, (HIV) Abscess/skin Success 234 6 M, 35, (HIV) Sinus Success 169 7 M, 32 Pulmonary Success 182 Conclusions: The successful outcomes of these 6 cases highlight a potential role of POS for salvage treatment of histoplasmosis, including cases failing standard therapy with other azoles, and suggests that POS could have promise as primary therapy. Further clinical studies are warranted.
Full conference title:
43rd Interscience Conference on Antimicrobial Agents
- ICAAC 43rd