Scedosporiosis and Lomentosporiosis
Also known as: Scedosporium Infection, Lomentospora prolificans, Pseudallescheria boydii
Scedosporium species and Lomentosporium prolificans (formerly Scedosporium prolificans) are hyaline moulds. The Scedosporium species are the asexual forms of Pseudallescheria species. They cause localised and invasive disease in the immunocompetent and the immunocompromised, and are intrinsically resistant to most antifungals, so mortality is high.
They live in soil, polluted and stagnant water, sewage, and manure, in temperate and subtropical regions (Europe, Australia, and the United States). They are common colonisers of the lungs in people with cystic fibrosis.
The main groups of disease are:
- Eumycetoma.
- Traumatic infection of skin, bone, and joint.
- Keratitis and endophthalmitis.
- Pulmonary colonisation and allergic disease in cystic fibrosis.
- Central nervous system infection after near drowning.
- Invasive and disseminated disease in immunocompromised hosts.
| Taxon | Notes |
|---|---|
| Scedosporium apiospermum (Pseudallescheria apiosperma) | Commonest in much of the world; pulmonary, mycetoma, central nervous system |
| Scedosporium boydii (Pseudallescheria boydii) | Common in the United States and Europe; eumycetoma and lung infection |
| Scedosporium aurantiacum | Prominent in Australia; cystic fibrosis lung disease and bone infection |
| Scedosporium dehoogii | Cystic fibrosis lung colonisation |
| Scedosporium minutisporum | Rare |
| Lomentosporium prolificans | A genus of its own, with resistance to nearly all drugs; frequent in Spain and Australia; fungaemia in neutropenia |
| Aspect | Details |
|---|---|
| Colony | Scedosporium apiospermum and Scedosporium boydii: fast growing, woolly, white to grey or brown, with a dark reverse, growing at 25 to 37 degrees Celsius and tolerating cycloheximide. Lomentosporium prolificans: very dark, grey to black, glabrous or with a mucoid texture, and a darker reverse |
| Microscopy | Septate hyaline to pale brown hyphae; Scedosporium has single celled conidia on short annellides, and Scedosporium boydii also forms coremia (synnemata) and a Graphium state; Lomentosporium prolificans has flask shaped annellides with an inflated base and a prominent tip, and conidia in clusters; no sexual state in Lomentosporium |
| Tissue | Hyaline septate hyphae with acute angle branching, indistinguishable from Aspergillus; hyphae with swollen forms; grains in mycetoma are white to yellow |
| Selective media | Media with cycloheximide allow Scedosporium to grow, and SceSel plus (with benomyl) is used for sputum in cystic fibrosis because it is rare for Aspergillus to grow on it |
| Blood cultures | Positive in invasive Lomentosporium prolificans in about 40 to 60 percent, and in Scedosporium less often |
| Identification | Sequencing of the beta tubulin gene (the preferred target) and internal transcribed spacer region, and mass spectrometry with an extended database |
| Biomarkers | Galactomannan is negative, and beta D glucan is often positive |
| Susceptibility testing | Reference broth microdilution without clinical breakpoints |
| Setting | Details |
|---|---|
| Near drowning | Aspiration of polluted water, with pneumonia, then brain abscess and meningitis days to weeks later |
| Trauma | Penetrating injury and soil contamination; eumycetoma, osteomyelitis, and septic arthritis |
| Cystic fibrosis | Lung colonisation in about 3 to 10 percent, with later allergic disease and, after lung transplant, invasive disease |
| Haematological malignancy and stem cell transplant | Invasive and disseminated disease, with Lomentosporium prolificans mainly in neutropenia |
| Solid organ and lung transplant | Disseminated disease; high mortality; a contraindication to lung transplant in some centres |
| Corticosteroid treatment and chronic granulomatous disease | Invasive disease |
| Ocular trauma and surgery | Keratitis and endophthalmitis |
| Haemodialysis and intravenous drug use | Catheter and endocarditis |
| Form | Features |
|---|---|
| Eumycetoma | Swelling, sinuses, and discharge of white to yellow grains, usually of the foot or lower leg, after trauma; bone involvement late |
| Cutaneous and subcutaneous | Nodules, abscesses, and ulcers after trauma, in the immunocompetent |
| Bone and joint | Osteomyelitis and septic arthritis after trauma or surgery |
| Keratitis and endophthalmitis | Corneal ulcer after trauma with soil or after surgery; vitreous involvement |
| Pulmonary colonisation and allergic bronchopulmonary disease | Chronic productive cough, wheeze, and bronchiectasis in cystic fibrosis, with fungal bronchitis and allergic disease similar to allergic bronchopulmonary aspergillosis |
| Fungal ball | In pre-existing cavities |
| Invasive pulmonary disease | Fever, cough, and nodules, cavities, or consolidation, similar to aspergillosis |
| Central nervous system | Brain abscess (multiple, often in a ring enhancing pattern) and meningitis, particularly after near drowning, and in the immunocompromised |
| Disseminated disease | Fever, fungaemia (mostly in Lomentosporium prolificans), skin lesions, endocarditis, and multiple organ involvement, with mortality of 70 to 90 percent in Lomentosporium prolificans |
| Condition | Points that separate it |
|---|---|
| Invasive aspergillosis | Positive galactomannan, culture, and susceptibility pattern |
| Fusariosis | Culture morphology and skin lesions |
| Mucormycosis | Broad aseptate hyphae |
| Eumycetoma from other agents | Grain colour and culture |
| Nocardiosis and actinomycetoma | Filamentous branching bacteria in grains, and modified acid fast stain |
| Allergic bronchopulmonary aspergillosis | Aspergillus specific tests |
| Tuberculosis and bacterial brain abscess | Culture and imaging |
| Drug | Scedosporium apiospermum complex | Lomentosporium prolificans |
|---|---|---|
| Voriconazole | Active in most (minimal inhibitory concentration 0.25 to 2); the drug of choice | Resistant in most (above 4 micrograms per mL) |
| Posaconazole | Variable | Resistant |
| Itraconazole | Variable | Resistant |
| Isavuconazole | Variable | Resistant |
| Amphotericin B | High minimal inhibitory concentrations and poor activity | Resistant |
| Echinocandins | Modest activity in some species | Resistant (some combination synergy) |
| Terbinafine | Some activity, used in combination | Some activity, used in combination |
| Flucytosine and fluconazole | Inactive | Inactive |
| Olorofim | Active in vitro and in clinical trial use | Active in vitro and in clinical trial use |
| Fosmanogepix | Active in vitro and in clinical trial use | Active in vitro and in clinical trial use |
Principles
Therapy combines antifungal treatment, surgery, and correction of immune defects, with susceptibility testing and species identification at the start. Surgery has a major role, because drugs act poorly alone.
Scedosporiosis
| Element | Details |
|---|---|
| First line | Voriconazole 6 mg per kg intravenously every 12 hours for 2 doses, then 4 mg per kg every 12 hours; oral 200 mg every 12 hours, increased to 300 mg by trough; trough 1 to 5.5 micrograms per mL, and 2 or higher in central nervous system disease |
| Alternatives | Posaconazole (delayed release tablets 300 mg every 12 hours on day 1, then 300 mg daily), and isavuconazonium sulphate (372 mg every 8 hours for 6 doses, then 372 mg daily) with limited data |
| Combination | Voriconazole with terbinafine (250 mg every 12 hours orally) or with an echinocandin (for example micafungin 100 to 150 mg daily) in severe, refractory, or central nervous system disease, with limited evidence |
| Amphotericin B | Not used alone because of poor activity |
| Surgery | Debridement of infected bone, joint, sinus, and soft tissue; drainage or excision of brain abscesses; excision of fungal balls; removal of infected devices; enucleation or vitrectomy in endophthalmitis |
| Reduction of immunosuppression | Needed, with neutrophil support in neutropenia |
| Eumycetoma | Voriconazole for months, and surgery; longer than for other fungal infections |
| Keratitis and endophthalmitis | Topical voriconazole 1 percent, with intravitreal voriconazole 100 micrograms per 0.1 mL, and systemic voriconazole, with surgery |
| Duration | At least 3 to 6 months, or longer for bone, central nervous system disease, and mycetoma, and until immune recovery |
| Cystic fibrosis | Treatment of allergic disease with corticosteroids and itraconazole or voriconazole, and prophylaxis for lung transplantation; the decision to treat colonisation is individual |
| Transplant | Pre-transplant and post-transplant antifungal therapy and secondary prophylaxis with voriconazole |
Lomentosporiosis
| Element | Details |
|---|---|
| Resistance | Nearly pan resistant, and no single agent is reliably effective |
| Recommended | Voriconazole combined with terbinafine (voriconazole at standard doses and terbinafine 250 mg every 12 hours), with or without a third drug (an echinocandin or liposomal amphotericin B); survival remains poor |
| New agents | Olorofim and fosmanogepix are active in vitro and in early clinical use, and access is through trials and compassionate use |
| Surgery | Excision of foci where possible |
| Immune support | Granulocyte colony stimulating factor and reduction of immunosuppression |
| Catheter | Remove central venous catheters |
| Outcome | Mortality is above 80 percent in disseminated disease |
Localised infection in immunocompetent hosts, including eumycetoma and keratitis after early treatment, has a reasonable outcome. Central nervous system infection has mortality of 50 to 70 percent or higher. Disseminated Scedosporium disease has mortality of 60 to 70 percent, and Lomentosporium prolificans has mortality of 80 to 90 percent in persistent immunosuppression.
Wound care after soil contamination and near drowning (with early broad cover in near drowning, including a mould active agent), avoidance of polluted water in immunocompromised patients, screening of sputum in patients with cystic fibrosis before transplant, and mould active prophylaxis with posaconazole or voriconazole in high risk patients, with limited efficacy in Lomentosporium prolificans.
