TABLE 2

Main characteristics and treatment recommendations for the most frequent non-Aspergillus moulds causing lung infections

Fungal agentMain speciesMicrobiological diagnosis [130]#TreatmentComments
Mucorales [71]Rhizopus spp., Mucor spp., Rhizomucor spp., Cunninghamella spp., Lichtheimia sp., Apophysomyces spp.Thick, ribbonlike, non-septate hyphae; no available biomarkers; molecular diagnosis (pan-fungal or quantitative species-specific PCR)Liposomal amphotericin B 5–10 mg·kg−1 per day (first choice) or isavuconazole (second choice); posaconazole (second line); liposomal amphotericin B combined with echinocandins or posaconazole in severe cases (low evidence)CT scan showing reverse halo sign, multiple nodes (>10) or pleural effusion; perform surgery whenever feasible; AST is recommended; rigorous glycaemic control; strategies to restore immunity; consider deferasirox in diabetic ketoacidosis; consider hyperbaric oxygen
Fusarium spp. [94]F. solani species complex, F. oxysporum species complex, F. verticillioides, F. fujikuroiNarrow, septate hyphae with acute angle branching (like Aspergillus spp.); canoe-shaped macroconidia; conidiophores with single or clustered conidia, with potential reniform adventitious conidia; galactomannan and 1,3-β-d-glucan may be positive; positive blood cultures in ∼50% of cases (adventitious sporulation); molecular diagnosisLiposomal amphotericin B or voriconazole; consider initial combination of both liposomal amphotericin B and voriconazole; adding an echinocandin or terbinafine may be considered in severe cases (very low evidence)Typically disseminated skin lesions; AST is recommended; perform surgery whenever feasible; strategies to restore immunity; importance of neutropenia recovery
Scedosporium spp. [94]S. apiospermum, S. aurantiacum, S. boydii, S. dehoogiiNarrow, septate hyphae with acute angle branching (like Aspergillus spp.); lateral branching off at 60–70° angle may be observed; annellides with a swollen base and elongated neck; oval conidia with truncated base; distinctive coremia or an ascocarp may be seen; molecular diagnosisVoriconazole (first line); echinocandins (second line); voriconazole combined with echinocandins or terbinafine in severe cases (low evidence)Consider performing MRI; resistant to amphotericin B; AST is recommended; perform surgery whenever feasible; strategies to restore immunity
Lomentospora prolificans (formerly known as Scedosporium prolificans) [94]Narrow, septate hyphae with acute angle branching (like Aspergillus spp.); black colour colonies; flask-shaped and annellated conidiogenous cells with a swollen base and elongated neck; smooth olive conidia cluster at the apex; molecular diagnosisVoriconazole (first line); consider voriconazole combined with terbinafine or/and echinocandins (very low evidence); consider the use of olorofim (current lack of evidence and not commercialised)Commonly resistant to all available antifungals; AST is recommended; consider performing cranial MRI; perform surgery whenever feasible; strategies to restore immunity
Other hyaline moulds [94]Paecilomyces spp., Acremonium spp., Rasamsonia spp., Penicillium spp., Trichoderma spp.Narrow, septate hyphae with acute angle branching (like Aspergillus spp.); some differences between species; molecular diagnosisOptimal antifungal therapy not established and depends on the isolated speciesImportance of molecular diagnosis and AST; perform surgery whenever feasible; strategies to restore immunity
Phaeohyphomycetes [94]Alternaria spp., Exophiala spp., Curvularia spp., Cladosporium spp., Ochroconis spp., Bipolaris spp.Septate hyphae with dark-pigmented colonies (melanin production); some differences between species; 1,3-β-d-glucan may be positive; molecular diagnosisOptimal antifungal therapy not established and depends on the isolated speciesAST is recommended; perform surgery whenever feasible; strategies to restore immunity

CT: computed tomography; AST: antifungal susceptibility testing; MRI: magnetic resonance imaging. #: microscopic morphology description is based on direct examination; : due to the very low quality of evidence available, some of these recommendations are based on the personal experience of the authors.