Mold-Associated Infections

Mold infections range in spectrum from colonization to hypersensitivity reactions. In addition, opportunistic molds have become increasingly recognized as a cause of life-threatening invasive infection in severely ill or immunocompromised patients.

Diagnosis

Diagnosis of Mold-Associated Syndromes

Pneumonia
Organism Recommended Testing
Hyaline molds

BAL with fungal stain and culture (A, F, S)

PCR for respiratory specimens and tissue (A)

Biopsy with fungal culture of tissue

Galactomannan (A) on BAL and serum

(1,3)-β-D-glucan (A, F, possibly S)

Zygomycetes

Biopsy tissue culture

Dematiaceous fungi

BAL

Biopsy tissue culture

A, Aspergillus fumigatus; BAL, bronchoalveolar lavage; F, Fusarium spp; PCR, polymerase chain reaction​; S, Scedosporium spp

Hypersensitivity
Organism Recommended Testing
Hyaline molds

Aspergillus fumigatus scratch test (A)

Serum IgE (A)

Aspergillus antibodies CF, ID (A)

Chest x-ray/CT scan (A)

Fungal balls – sputum culture + Aspergillus antibodies CF, ID (A)

Zygomycetes

n/a

Dematiaceous fungi

n/a

A, Aspergillus fumigatus; CF, complement fixation; CT, computed tomography; ID, immunodiffusion; n/a, not available
Ophthalmic
Organism Recommended Testing
Hyaline molds

Culture (A, F, S)

Zygomycetes

Culture

Dematiaceous fungi

Culture

A, Aspergillus fumigatus; F, Fusarium spp; S, Scedosporium spp
Otorhinolaryngologic
Organism Recommended Testing
Hyaline molds

Ball of hyphae with obstruction

  • CT scan/MRI and culture (A, F, S)

Acute invasive rhinosinusitis – associated with invasive disease

  • CT scan/MRI and fungal culture of tissue (A, F, S)

PCR for respiratory specimens and tissue (A)

Zygomycetes

Fungal culture of tissue

Dematiaceous fungi

Allergic – CT scan/MRI with lack of invasion

Acute invasion – CT scan/MRI and fungal culture of tissue

A, Aspergillus fumigatus; CT, computed tomography; F, Fusarium spp; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; S, Scedosporium spp
Central Nervous System
Organism Recommended Testing
Hyaline molds

CSF – stain and culture (A, F, S)

Zygomycetes

Fungal culture of tissue

Dematiaceous fungi

Fungal culture

A, Aspergillus fumigatus; CSF, cerebrospinal fluid; F, Fusarium spp; S, Scedosporium spp
Cardiac/Mediastinum
Organism Recommended Testing
Hyaline molds

Blood culture (A, F, S)

Galactomannan antigen (A)

(1,3)-β-D-glucan (A, F, possibly S)

Zygomycetes

Blood culture (rarely positive A or S)

Dematiaceous fungi

n/a

A, Aspergillus fumigatus; F, Fusarium spp; n/a, not available; S, Scedosporium spp
Hepatosplenic or Gastrointestinal (GI) System
Organism Recommended Testing
Hyaline molds

n/a

Zygomycetes

Fungal culture of tissue

Dematiaceous fungi

n/a

Dermatologic
Organism Recommended Testing
Hyaline molds

Fungal stain and culture of pus (A, F, S)

PCR for respiratory specimens and tissue (A)

Zygomycetes

Fungal stain and culture

Dematiaceous fungi

Fungal stain and culture

A, Aspergillus fumigatus; F, Fusarium spp; PCR, polymerase chain reaction; S, Scedosporium spp
Bone
Organism Recommended Testing
Hyaline molds

Bone marrow culture (A, F, S)

Zygomycetes

Bone marrow culture

Dematiaceous fungi

Mycetoma – stain of pus

A, Aspergillus fumigatus; F, Fusarium spp; S, Scedosporium spp
Disseminated/Invasive
Organism Recommended Testing
Hyaline molds

Blood culture (A, F, S)

Galactomannan antigen (A)

Zygomycetes

Blood culture

Dematiaceous fungi

n/a

A, Aspergillus fumigatus; F, Fusarium spp; S, Scedosporium spp

Differential Diagnosis

Monitoring

  • Galactomannan antigen
    • May be used to monitor immunocompromised patients who are experiencing neutropenia
      • Limited sensitivity in nonneutropenic patients
    • Requires a moderate prevalence of invasive aspergillosis in the community; not as useful for monitoring if prevalence is low
  •  (1,3)-β-D-glucan (Fungitell)
    • May be used to monitor immunocompromised patients who are experiencing neutropenia; most experience is with monitoring for invasive aspergillosis and candidiasis
    • Test has high negative predictive value; false negatives uncommon

Background

Epidemiology

Invasive fungal disease occurs most commonly in immunocompromised patients

Etiology

  • Molds most often associated with significant disease include
    • Hyaline molds (three most common)
      • Aspergillus fumigatus (A)
      • Fusarium spp (F)
      • Scedosporium spp (S)
    • Zygomycetes
      • Hallmarks of Zygomycetes infection are vascular invasion and tissue necrosis (presence of black tissue)
    • Dematiaceous fungi
      • Includes a large group of darkly pigmented organisms

Risk Factors

At Risk for Infection
Organism Risk Group
Hyaline molds

All immunocompromised

Special risk

Zygomycetes

All immunocompromised

Special risk

Dematiaceous fungi

All immunocompromised

ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia

Mold-Associated Symptoms – Pulmonary

Pneumonia
Organism Disease/Syndrome
Hyaline molds

Acute respiratory distress syndrome

Chronic inflammatory process in colonized cystic fibrosis patients (A, S)

Necrotizing pneumonias – halo, crescent signs (A)

Pulmonary mycetoma (S)

Rapidly progressive consolidation

Zygomycetes

Infiltrate or cavity on x-ray

Hemoptysis

Necrotizing pneumonias

Mycotic pulmonary aneurysms

Dematiaceous fungi

Rare pulmonary dematiaceous disease

A, Aspergillus fumigatus; ,S, Scedosporium spp
Hypersensitivity
Organism Disease/Syndrome
Hyaline molds

Endobronchial Scedosporium and Aspergillus – fungal balls (A, S)

Allergic bronchopulmonary aspergillosis and Scedosporium pneumonia (A, S)

Asthma (A)

Zygomycetes

n/a

Dematiaceous fungi

n/a

A, Aspergillus fumigatus; S, Scedosporium spp

Mold-Associated Symptoms – Nonpulmonary

Ophthalmic
Organism Disease/Syndrome
Hyaline molds

Endophthalmitis (A, S)

Keratitis (A, F)

Zygomycetes

Orbital invasion from sinus

Dematiaceous fungi

Keratitis

A, Aspergillus fumigatus; F, Fusarium spp; S, Scedosporium spp
Otorhinolaryngologic
Organism Disease/Syndrome
Hyaline molds

Otomycosis – growth on cerumen, detritus in ear canal (A, F, S)

Sinus (A, F, S)

  • Ball of hyphae with obstruction
  • Acute invasive rhinosinusitis
  • Chronic fibrosing granulomatous inflammation with tissue invasion
Zygomycetes

Orbital cellulitis

Cranial nerve palsies

Cavernous sinus and internal artery thromboses

Invasive rhinosinusitis

Dematiaceous fungi

Allergic fungal sinusitis

Acute invasive rhinosinusitis

A, Aspergillus fumigatus; F, Fusarium spp; S, Scedosporium spp
Central Nervous System
Organism Disease/Syndrome
Hyaline molds

Brain abscess (A, F, S)

Meningitis – rare (A, F, S)

Vascular infarcts in brain (A)

Zygomycetes

Brain abscesses – generally invasive from sinuses

Meningitis – rare

Dematiaceous fungi

Rare CNS dissemination, brain abscesses, meningitis

A, Aspergillus fumigatus; CNS, central nervous system; F, Fusarium spp; S, Scedosporium spp
Cardiac/Mediastinum
Organism Disease/Syndrome
Hyaline molds

Endocarditis (A, F, S)

Pericarditis (A, F, S)

Zygomycetes

Endocarditis

Dematiaceous fungi

n/a

A, Aspergillus fumigatus; F, Fusarium spp; S, Scedosporium spp
Hepatosplenic or Gastrointestinal (GI) System
Organism Disease/Syndrome
Hyaline molds

Peritonitis – rare (S)

Zygomycetes

Ulcers – all portions of GI tract

Stomach most commonly affected

Dematiaceous fungi

n/a

S, Scedosporium spp
Dermatologic
Organism Disease/Syndrome
Hyaline molds

Onychomycosis (A, F, S)

Invasion of catheters (A, F)

Burns (A)

Necrotic skin lesions (S)

Papules, nodules (tender) (F)

Zygomycetes

Ulcers

Necrosis

Dematiaceous fungi

Blastomycosis nodules that become verrucous lesions and plaques

Mycetoma – usually lower extremity; single red nodule

  •  Draining sinus tract, extrusion of granules

Chronic dematiaceous fungi – may lead to squamous cell carcinoma

A, Aspergillus fumigatus; F, Fusarium spp; S, Scedosporium spp
Bone
Organism Disease/Syndrome
Hyaline molds
 

Vertebral (A most common, S)

Long bones and joints (S)

Zygomycetes

Rare bone necrosis

Dematiaceous fungi

n/a

A, Aspergillus fumigatus; S, Scedosporium spp

ARUP Laboratory Tests

Test for Aspergillus as cause of pulmonary disease

A negative test may not rule out clinical allergy or even anaphylaxis

For the direct detection and identification of fungi in tissue

Adjunct test for the diagnosis of invasive mucormycosis caused by the most common Mucorales genera. Does not replace culture and histopathology.

Detect Aspergillus species and differentiate Aspergillus fumigatus

Aid in the diagnosis of invasive/disseminated aspergillosis

Negative results do not rule out invasive aspergillosis

Many agents may cross-react with test (food, antibiotics, etc)

Recommend serial sampling for high-risk patients if suspicion is high

Single positive test result (index ≥0.5) should be confirmed by separate serum specimen

Aid in the diagnosis of pulmonary aspergillosis

Gold standard test to diagnose fungi as agent of infection

Identify fungus using fungal smear (eg, yeast, aseptate hyphae, septate hyphae)

Identify fungi from culture

Testing to differentiate between Candida albicans and C. dubliniensis performed by request only 

Gold standard test to diagnosis fungi as agent of infection in blood

Aid in the diagnosis of invasive/disseminated fungal infections (eg, Pneumocystis jirovecii, Aspergillus, or Candida)

Does not detect fungal species that produce very low levels of (1,3)-β-D-glucan (eg, Cryptococcus)

Does not detect Zygomycetes spp, which are not known to produce (1,3)-β-D-glucan (eg, AbsidiaMucorRhizopus)

In addition, the yeast phase of Blastomyces dermatitidis may not be detected by the assay

Aid in diagnosing allergic bronchopulmonary aspergillosis (ABPA)

Not appropriate for diagnosing invasive aspergillosis

Determine in vitro susceptibility to antifungal agents for fungal organisms

Agents tested include amphotericin B, anidulafungin, caspofungin, fluconazole, 5-fluorocytosine, itraconazole, micafungin, posaconazole, and voriconazole

Selective reporting by organism

Related Tests

Not recommended for the diagnosis of invasive aspergillosis

Consider ordering an aspergillus galactomannan antigen test (serum or bronchoscopy)

Negative fungal serology does not rule out the possibility of current infection

Not recommended for the diagnosis of invasive aspergillosis

Consider ordering an aspergillus galactomannan antigen test (serum or bronchoscopy) 

For suspicion of coccidioidal meningitis, refer to coccidioides antibodies panel for cerebrospinal fluid (CSF)

Not recommended for the diagnosis of fungal infection of the central nervous system

Refer to individual fugal antibody tests, as relevant to patient exposure(s)

Not recommended

Refer to individual fugal antibody tests, as relevant to patient exposure(s)

Limited clinical utility

Best evidence for infection is significant change on 2 appropriately timed specimens where both tests are done in the same laboratory at the same time; however, low levels of IgM may occasionally persist for >12 months

Identify fungi from culture

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories
Contributor

Slev

Patricia R. Slev, PhD
Associate Professor of Clinical Pathology, University of Utah
Section Chief, Immunology; Medical Director, Immunology Core Laboratory, ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®