Table 1. Hyalohyphomycosis*: Spectrum of Infection of Most Common Pathogens
|
Pathogen |
Normal host |
Immunosuppressed host |
Fusarium spp. |
Keratitis Endophthalmitis Bone/joint infection Skin infection Onychomycosis Mycetoma Peritonitis (CAPD) |
Disseminated Sinusitis Pneumonia Cellulitis Endophthalmitis |
|
Scedosporium spp. |
Sinusitis Keratitis Endophthalmitis Skin and soft tissue infection Osteomyelitis Brain abscess and meningitis |
Disseminated infection Sinusitis Pneumonia Brain abscess and meningitis |
|
Scopulariopsis spp. |
Onychomycosis Keratitis Otomycosis Prosthetic valve endocarditis |
Disseminated infection Sinusitis Pneumonia Cellulitis |
|
Paecilomyces spp. |
Sinusitis Keratitis Onychomycosis Endocarditis Otitis Cellulitis Peritonitis (CAPD) |
Disseminated infection Pneumonia Pyelonephritis Cellulitis Osteomyelitis |
|
Acremonium spp. |
Keratitis Onychomycosis Osteomyelitis/septic arthritis Meningitis Endophthalmitis |
Disseminated infection Peritonitis Cerebritis Pneumonia Dialysis-access fistula infection |
CAPD: Continuous abdominal peritoneal dialysis
* Penicillium marneffii is discussed in a separate chapter.
Table 2. In Vitro Antifungal Susceptibility of Common Agents of Hyalohyphomycosis and Drug of Choice
|
Pathogen |
Amphotericin B |
Caspofungin |
Fluconazole |
Voriconazole |
Itraconazole |
Natamycin |
|
Fusarium spp |
Variable * |
Resistant |
Resistant |
Variable* |
Variable† |
Susceptible, topical alone† |
|
S. apiospermium ¨ |
Susceptible |
Intermediate-Susceptible |
Susceptible |
Susceptible† |
NT |
|
|
S. inflatum ¨ |
Resistant |
NT |
Resistant |
Resistant |
Resistant |
NT |
|
P. lilacinus ª |
Intermediate |
NT |
NT |
Susceptible |
Susceptible† |
NT |
¨Scedosporium ªPaecilomyces
NT: not tested. * Variable: May be species or strain specific. †denotes drug of choice
Topical natamycin application for fusarial keratitis; Natamycin not available as a systemic agent.
Miconazole has activity against S. apiospermum and P. lilacinus, but is associated with significant toxicity. Ketoconazole is moderately active against S. apiospermum and P. lilacinus but has erratic bioavailability. Other triazoles such as Itraconazole and voriconazole are more potent, safer, have oral and intravenous formulations and thus are more appropriate therapeutic agents.
Flucytosine has no activity against Fusarium spp, S. apiospermium and S. inflatum.
Table 3. Dosing Schedule of
Antifungal Agents with Activity Against Hyalohyphomycosis
Agent
Standard daily dose
Maximal daily dose
Polyenes
Amphotericin B
1 mg/kg
1.5 mg/kgÅ
Liposomal Amphotericin B (Ambisome)
3-5 mg/kg
15 mg/Kg
Amphotericin Lipid Complex
3-5 mg/kg
Amphotericin Colloidal Dispersion
3-5 mg/kg
Triazoles
Fluconazole
400 mg
1600 mg
Itraconazle*
400 mg in 2 doses after loading§
800 mg
Voriconazole*
6 mg/kg in 2 doses after loading§
Echinocandins
Caspofungin
70 mg loading then 50 mg
* Use IV formulation in critically ill patients.
§ Loading dose: Itraconazole: 400 mg BID for three days; Voriconazole: 6 mk/kg for two doses.
Å rarely tolerated at this dose
Table 4. Management of Specific Hyalohyphomycosis
|
Pathogen |
Normal host |
Immunosuppressed host |
|
Fusarium spp. |
Keratitis: topical natamycin 5.0% suspension. Endophthalmitis: vitrectomy, intravitreal Amphotericin B, and systemic itraconazole or voriconazole. Enucleation in severe cases. Skin and soft tissue: surgical drainage. Onychomycosis: avulsion of nail, topical natamycin on open lesions? Osteomyelitis: surgical debridement, systemic antifungal agents (Amphotericin B or its lipid formulations, itraconazole, voriconazole) |
Systemic antifungal agents: IV Amphotericin B, or its lipid formulations; newer triazoles (itraconazole, voriconazole). Reversal of immunosuppression. Surgery if localized infection. Venous catheter removal in the rare case of catheter related fungemia. |
|
Scedosporium apiospermium |
Localized lesion: surgery. Itraconazole, voriconazole. Endophthalmitis: vitrectomy, intravitreal Amphotericin B, and systemic itraconazole or voriconazole. Enucleation in extreme cases. Arthritis: intraarticular injection of Amphotericin B. |
Reversal of immunosuppression. Localized infection: surgery. Itraconazole, or voriconazole.
|
|
Scedosporium inflatum |
Localized infection: surgery.
|
Reversal of immunosuppression. Localized infection: surgery. |
|
Paecilomyces lilacinus |
Skin and soft tissue infection: surgical debridement and drainage. Endophthalmitis: vitrectomy, intravitreal Amphotericin B, and systemic itraconazole or voriconazole. Enucleation in severe cases. |
Reversal of immunosuppression. Localized infection: surgery. Itraconazole or voriconazole. |
|
· Hemoptysis from a single cavitary lung lesion (always perform a computerized chest scan to search for other lesions). · Progressive cavitary lung lesion (always perform a computerized chest scan to search for other lesions). · Infiltration into the pericardium, great vessels, bone or thoracic soft tissue. · Progressive sinusitis. · Osteomyelitis, septic arthritis. · Endophthalmitis. · Resection of infected / colonized tissue prior to commencing immunosuppressive agents to prevent dissemination after cytotoxic therapy. |
Table 6. Reversal of Immunosuppression: Potentially Useful Strategies in Patients with Invasive Hyalohyphomycosis
|
· Discontinuation / dose reduction of immunosuppressive agents (corticosteroids, other cytotoxic agents) · Recombinant cytokines: -granulocyte-colony stimulating factors (G-CSF) -granulocyte monocyte-colony stimulating factors -gamma interferon. · Stem cell reconstitution with infusion of autologous bone marrow/peripheral stem cells product in the event of progressive infection in patients with severe, uncontrollable, graft versus host disease. · Granulocyte transfusions (stimulated with G-CSF and dexamethasone). |