Fusariosis

OVERVIEW

• Fusarium infections are serious fungal infections primarily affecting immunocompromised patients.
• They can present as superficial, locally invasive, or disseminated infections.
• Localised disease is typical in immunocompetent, whereas disseminated disease is exclusive to immunosuppressed patients.
• High mortality rates, especially in disseminated disease.

CAUSE

• Caused by Fusarium species (>300 exist), a group of filamentous fungi (aka molds).
• Commonly found in soil, water (including seawater and hospital water systems), and organic matter.
• Fusarium species are recognised as plant pathogens (e.g. cereals) and aquatic animals such as dolphins, seahorses, and turtles.

Risk factors

• Immunocompromised states (e.g., hematologic malignancies, neutropenia, organ transplantation).
• Prolonged use of corticosteroids.
• Broad-spectrum antibiotic use.
• Traumatic inoculation (e.g., burns, surgery).
• If fungal keratitis: trauma, contact lenses

PATHOGENESIS

• Fusarium species enter the body through inhalation, ingestion, or direct inoculation.
• Common superficial infections include onychomycosis and fungal keratitis
• after the inhalation of conidia (spores), hyphae form in the alveoli, resulting in inflammation and bronchial dissemination. Hyphase can invade blood vessels, causing thrombosis and tissue infarction.
• In immunocompromised patients, the fungus can cause fungaemia and disseminate via the bloodstream.
• Complications include:
  • Local invasion (e.g. cellulitis, lymphangitis)
  • Disseminated infection (50-70% mortality)
  • Metastatic skin lesions (60-80% in disseminated cases).
  • Respiratory tract involvement (30-50%), including  sinusitis, pneumonia, allergic sinusitis and allergic bronchopulmonary disease.
  • Mycotoxicosis can occur from ingesting fungal toxins from infected plants (e.g. cereals)

Clinical spectrum of invasive fusariosis (Nucci and Anaissie, 2023):

Immunocompetent patients	Immunocompromised patients
Skin and soft tissue infection	Disseminated disease
Osteomyelitis	Pneumonia
Arthritis	Fungemia
Endophthalmitis	Sinusitis
Peritonitis	Brain abscess
Endocarditis	Endocarditis
Eumycetoma	Osteomyelitis
Sinusitis	Arthritis
Pneumonia	Endophthalmitis
Fungemia
Disseminated disease

CLINICAL ASSESSMENT

HISTORY

• Symptoms may vary according to site infected and immunocompetence, e.g. fever, skin lesions, myalgia, cough, dyspnea, chest pain.
• Key questions: Recent chemotherapy, corticosteroid use, history of neutropenia, recent trauma or surgery.

EXAMINATION

• Signs may vary according to site infected and immunocompetence,
• General: Fever, signs of sepsis.
• Skin: Painful, erythematous nodules or necrotic lesions.
• Respiratory: Signs of pneumonia.

INVESTIGATIONS

BEDSIDE TESTS

• Blood gas
• Blood glucose
• POCUS: e.g. pleural effusions, abscesses.

LABORATORY TESTS

• Blood cultures: positive in disseminated disease (50-70%) (more common than for aspergillosis)
• Fungal cultures: skin swabs, sputum/ BAL samples
• PCR: Detect Fusarium DNA.
• May have positive Aspergillus galactomannan (GMI) test and/or ,3-beta-D-glucan (BDG) test in the seum

IMAGING

• CXR: Pulmonary infiltrates, nodules, effusions
• CT chest: better delineation of pulmonary involvement; pan scan if ddiseminated disease.

OTHER

• Histopathology: Tissue biopsy showing hyphae.

MANAGEMENT

RESUSCITATION

• Coordinated team-based approach to resuscitation in an appropriately equipped setting to address the following life threats:
  • If SpO2 <90%, then administer supplemental oxygen.
  • If hypotension, then administer IV fluids and vasopressors.
  • If sepsis, then initiate broad-spectrum antibiotics and antifungals.

SPECIFIC MANAGEMENT

• Antifungal therapy: Voriconazole 6 mg/kg IV q12h for 1 day, then 4 mg/kg IV q12h.
  • Alternative is lipid formulation of amphotericin B (liposomal amphotericin B—3 mg/kg daily; amphotericin B lipid complex—5 mg/kg daily)
  • Combined therapy is also an option
  • intravitreal antifungals may be required if endophthalmitis
• Surgical debridement: For localized infections.
• Secondary prevention: patients with prior invasive fusariosis who will undergo additional immunosuppressive therapies receive secondary prophylaxis (mold-active azole or a lipid formulation of amphotericin B).

SUPPORTIVE CARE

• FASTHUGSINBED please
• Consider G-SCF (e.g. if neutropenia)

SEEK & TREAT COMPLICATIONS

• Monitor for and treat:
  • Disseminated infection.
  • Respiratory failure.
  • Septic shock.

DISPOSITION

• ICU admission for severe cases.
• Consult infectious disease specialists.
• Consider consultation for underlying conditions (e.g. hematology, oncology, transplant physicians) and source control (e.g. surgeons)

PROGNOSIS

• Negative prognostic factors:
  • Neutropenia duration.
  • Corticosteroid therapy
  • Extent of infection.
  • Poor response to antifungal therapy.
• Mortality: 50-70% in disseminated disease.

CONTROVERSIES

• Optimal antifungal therapy given limited data on efficacy and Fusarium species tend to have high minimum inhibitory concentrations (MICs) to most antifungal agents
• Role of combination antifungal therapy.

PRACTICAL TIPS

• Early recognition and treatment are crucial.
• Regular monitoring for complications.
• Multidisciplinary approach for management.

CONCLUSION

• Fusariosis is potentially life-threatening, especially in immunocompromised patients.
• A high index of suspicion leading to early diagnosis and aggressive antifungal treatment improves outcomes, however, invasive fusariosis largely depends on the recovery of immunosuppression (especially neutrophil recovery if neutropaenic)

REFERENCES

FOAM and web resources

• LITFL CCC
  • Nickson C. Fungi and antifungal agents. LITFL.com, 2021.

Journal articles

• Demonchy J, Biard L, Clere-Jehl R, Wallet F, Mokart D, Moreau AS, Argaud L, Verlhac C, Pène F, Lautrette A, Bige N, de Jong A, Canet E, Quenot JP, Issa N, Zerbib Y, Bouard I, Picard M, Zafrani L. Multicenter Retrospective Study of Invasive Fusariosis in Intensive Care Units, France. Emerg Infect Dis. 2024 Feb;30(2):215–24. doi: 10.3201/eid3002.231221. PMID: 38270146; PMCID: PMC10826781.
• Nucci M, Anaissie E. Invasive fusariosis. Clin Microbiol Rev. 2023 Dec 20;36(4):e0015922. doi: 10.1128/cmr.00159-22. Epub 2023 Nov 8. PMID: 37937988; PMCID: PMC10732078.