Salvage Treatment for Invasive Aspergillosis and Mucormycosis: Challenges, Recommendations and Future Considerations

Abstract

Invasive mold diseases are devastating systemic infections which demand meticulous care in selection, dosing, and therapy monitoring of antifungal drugs. Various circumstances regarding PK/PD properties of the applied drug, resistance/tolerance of the causative pathogen or host intolerability can lead to failure of the initial antifungal therapy. This necessitates treatment adaption in the sense of switching antifungal drug class or potentially adding another drug for a combination therapy approach. In the current state of drastically limited options of antifungal drug classes adaption of therapy remains challenging. Current guidelines provide restricted recommendations only and emphasize individual approaches. However, novel antifungals, incorporating innovative mechanisms of action, show promising results in late stage clinical development. These will expand options for salvage therapy in the future potentially as monotherapy or in combination with conventional or other novel antifungals. We outline current recommendations for salvage therapy including PK/PD considerations as well as elucidate possible future treatment options for invasive aspergillosis and mucormycosis.

Keywords: aspergillosis; invasive fungal infections; mucormycosis; salvage therapy.

Figure 1

Present salvage therapy recommendations for invasive aspergillosis/ mucormycosis and additional future options. *Voriconazole (4–6mg/kg/d), isavuconazole (3x 200mg d1+2, then 200mg qd), posaconazole (300mg b.i.d. day 1 table/IV then 300mg qd) caspofungin (70mg/d IV day 1 then 50mg/d), micafungin (100mg - 150mg/d), anidulafungin (200mg qd day1 the 100mg qd).