Background: IFIs are an important cause of morbidity and mortality in immunocompromised patients. Current therapy, even with voriconazole (VORI), the most recently approved azole antifungal agent, provides insufficient therapeutic benefit; thus, many patients require salvage therapy. We discuss the efficacy of POS, an extended-spectrum azole antifungal, for the treatment of IFIs not responsive to VORI. Methods: A large open-label multicenter clinical trial of oral POS 800 mg/day in divided doses was conducted in patients intolerant of, or with disease refractory to, other antifungal therapy. In all, 8/330 patients had IFIs that did not respond to previous therapy, which included VORI. All 8 had refractory IFIs-7 proven and 1 probable. Complete or partial response was considered success; stable or persistent disease was non-success. Results: POS therapy was successful in 50% (4/8) of patients. Successful outcomes were seen in 50% (3/6) of patients with aspergillosis and included infections in lung (1), sinus (1), and disseminated disease (4) in immunocompromised patients. The other 2 patients had invasive candidiasis (non-success) and invasive histoplasmosis (success). Cumulative duration of previous VORI therapy ranged from 19 to 249 days. POS treatment duration ranged from 2 days to >1 year and was well tolerated. Conclusions: In this salvage therapy study, POS resulted in successful outcomes in 4/8 patients with IFIs not responsive to VORI. These cases support in vitro data indicating that some fungi resistant to VORI remain susceptible to POS. Thus, POS may provide a therapeutic option for IFIs refractory to VORI.
Full conference title:
44th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 44th