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.

Metagenomic next-generation sequencing could play a pivotal role in validating the diagnosis of invasive mold disease of the central nervous system

“…Aspergillus and Mucormycetes spp remain the primary causes of IMD ( Pana et al., 2017 ; Egger et al., 2023 ). Moulds are ubiquitous organisms that can be found in soil, water, and decaying vegetation ( McCarthy et al., 2014 ).…”

“…Invasive aspergillosis and mucormycosis are the two most common types of IMD, with mortality rates exceeding 30% even with appropriate treatment. The most common site of IMD infection is the lungs, while central nervous system invasive mold disease (CNS IMD) is less common, accounting for only 1% of all cases ( Egger et al., 2023 ). Due to the nonspecific clinical features of CNS IMD and the lack of efficient diagnostic methods, diagnoses are often delayed.…”

Mortality in ICU Patients with COVID-19-Associated Pulmonary Aspergillosis

“…On the other hand, even higher rates of azole resistance have been reported for environmental samples, such as 13.9% in Tanzania and 9.3% in Colombia [ 75 ]. The emergence of azole-resistant environmental isolates is particularly concerning as they can serve as a potential reservoir for resistant strains that can then infect humans or animals, contributing to IPA treatment failure and increasing IPA mortality [ 76 ]. Therapeutic drug monitoring (TDM) is an essential tool that should be considered when using antifungal agents to treat patients with CAPA [ 13 , 69 ].…”

A Systematic Review of the Therapeutic Outcome of Mucormycosis

“…Posaconazole and isavuconazole are the only available oral agents active against Mucorales [ 33 ]. Both these azoles have been used for salvage treatment when the use of amphotericin B is not possible or contraindicated [ 18 , 33 ].…”

“…Posaconazole and isavuconazole are the only available oral agents active against Mucorales [ 33 ]. Both these azoles have been used for salvage treatment when the use of amphotericin B is not possible or contraindicated [ 18 , 33 ]. Posaconazole (n = 250) and isavuconazole (n = 65) were used as monotherapy in some studies, with corresponding mortality rates of 17.2% and 24.6%, respectively.…”