Scedosporiosis and lomentosporiosis: modern perspectives on these difficult-to-treat rare mold infections

Abstract

SUMMARYAlthough Scedosporium species and Lomentospora prolificans are uncommon causes of invasive fungal diseases (IFDs), these infections are associated with high mortality and are costly to treat with a limited armamentarium of antifungal drugs. In light of recent advances, including in the area of new antifungals, the present review provides a timely and updated overview of these IFDs, with a focus on the taxonomy, clinical epidemiology, pathogenesis and host immune response, disease manifestations, diagnosis, antifungal susceptibility, and treatment. An expansion of hosts at risk for these difficult-to-treat infections has emerged over the last two decades given the increased use of, and broader population treated with, immunomodulatory and targeted molecular agents as well as wider adoption of antifungal prophylaxis. Clinical presentations differ not only between genera but also across the different Scedosporium species. L. prolificans is intrinsically resistant to most currently available antifungal agents, and the prognosis of immunocompromised patients with lomentosporiosis is poor. Development of, and improved access to, diagnostic modalities for early detection of these rare mold infections is paramount for timely targeted antifungal therapy and surgery if indicated. New antifungal agents (e.g., olorofim, fosmanogepix) with novel mechanisms of action and less cross-resistance to existing classes, availability of formulations for oral administration, and fewer drug-drug interactions are now in late-stage clinical trials, and soon, could extend options to treat scedosporiosis/lomentosporiosis. Much work remains to increase our understanding of these infections, especially in the pediatric setting. Knowledge gaps for future research are highlighted in the review.

Keywords: Lomentospora; Scedosporium; fungi.

Fig 1

Phylogenetic tree of Scedosporium species based on 60 representative strains from which TUB (exon 5 and 6) sequences are available, representing the known genetic variation within the genus, using Maximum Likelihood with the K2 + G model and 500 bootstrap replications. Bootstrap values > 50 are indicated below the tree branches. The tree is rooted with the outgroup species Petriellopsis africana and Lomentospora prolificans. GenBank accession numbers are shown in brackets. Bold font indicates sequences of type or reference strains. The frequency of strains is denoted by symbols: the most common causative strain, occasional occurrence, and rare occurrence.

Fig 2

Worldwide distribution of scedosporiosis (published cases between 2008 and 2023). Map created with MapChart [Creative Commons Attribution-ShareAlike 4.0 International License (CC BY-SA 4.0)].

Fig 3

Worldwide distribution of lomentosporiosis (published cases between 2008 and 2023). Map created with MapChart [Cell-wall-associated factors Creative Commons Attribution-ShareAlike 4.0 International License (CC BY-SA 4.0)].

Fig 4

Host immune response against Scedosporium spp. and Lomentospora prolificans α-glucan = alpha-glucan; CD = cluster of differentiation; CLR = C-type lectin receptors; GlcCer = glucosylceramide; GM-CSF = granulocyte-macrophage colony-stimulating factor; IFN-γ=interferon-gamma; IL-6 = interleukin-6; IL-8 = interleukin-8; IL-15 = interleukin-15; MR = Mannose Receptor; PMN = polymorphonuclear leukocytes; PRM = peptidorhamnomannan; ROS = reactive oxygen species; TLR = toll-like receptor; TNF-α=tumor necrosis factor-alpha; Th = T helper; Tc = T cytotoxic; Treg = regulatory T cells. The image was originally designed with BioRender and enhanced by Patrick Lane (ScEYEnce Studios).

Fig 5

Clinical and radiological presentations. Scedosporium apiospermum (A) cerebral abscess after near drowning, (B) skin, (C) spleen, and (D) lung lesions of a neutropenic patient with disseminated lomentosporiosis. (E) Thoracic computed tomography: right lobar pulmonary artery (thin arrow) and left pulmonary artery (thick arrow) partially thrombosed mycotic aneurysms.

Fig 6

Marcoscopic morphology of Scedosporium spp. and Lomentospora prolificans. Flat spreading olive-gray to black suede-like (A) surface and (B) reverse of Lomentospora prolificans on Sabouraud dextrose agar after 5 days of growth at 30°C. Expanding cottony grayish-white colony with a white, lobate margin, (C) surface and (D) reverse of Scedosporium apiospermum on Sabouraud dextrose agar after 5 days of growth at 30°C. Expanding cottony grayish-white colony with a light-yellow diffusible pigment, (E) surface and (F) reverse of Scedosporium aurantiacum on Sabouraud dextrose agar after 5 days of growth at 30°C.

Fig 7

Mircoscopic morphology of Scedosporium spp. and Lomentospora prolificans. Microscopic morphology of (A) Lomentospora prolificans showing smooth-walled ovoid to pyriform single-celled conidia (3–7 × 2–5 µm) borne in small groups on basally swollen flask-shaped conidiophores (arrow); and (B) Scedosporium apiospermum showing simple long conidiophores (arrow) bearing single-celled, pale brown ovoid-shaped conidia (5–7 × 4–6 µm).

Fig 8

Antifungal treatment pathway for an adult diagnosed with scedosporiosis. *The Australasian guideline recommends against the use of itraconazole and AmB formulations while the ECMM guideline recommends against the use of LAmB (43, 599). Clinicians should always tailor the use of antifungal therapies based on the patient’s clinical status. AmB = amphotericin B; ECMM = European Confederation of Medical Mycology; GM-CSF = granulocyte-macrophage colony-stimulating factor; LAmB = liposomal amphotericin B.

Fig 9

Antifungal treatment pathway for an adult diagnosed with lomentosporiosis. *Both ECMM and Australasian guidelines recommend against the use of LAmB (43, 599). Clinicians should always tailor the use of antifungal therapies based on the patient’s clinical status. ECMM = European Confederation of Medical Mycology; LAmB = liposomal amphotericin B.