Yeast-Associated Infections

Diagnosis

Indications for Testing

  • At-risk patients with suspected yeast-associated disease

Laboratory Testing

Respiratory – acute primary infection
Respiratory – Acute Primary Infection
Histoplasma
  • Sputum fungal stain
  • Histoplasma EIA serum and/or urine
  • Tissue culture
Cryptococcus
  • Fungal stain
  • Serum Cryptococcus antigen
  • Culture

Candida

  • Tissue biopsy specimen showing invasion
  • Tissue culture

Coccidioides

  • Sputum fungal stain
  • Tissue culture
  • Serum ID
Blastomyces
  • Sputum fungal stain
  • Serum ID, CF, EIA
  • Tissue culture
  • Antigen (serum, urine) as secondary test
Trichosporon or Rhodotorula

N/A

Respiratory – chronic pulmonary disease
Respiratory – Chronic Pulmonary Disease
Histoplasma
  • EIA serum or urine
  • Tissue culture
  • Antibody detection
Cryptococcus

N/A

Candida

N/A

Coccidioides

N/A

Blastomyces
  • Serum CF, ID, EIA
Trichosporon or Rhodotorula

N/A

Central nervous system
Central Nervous System
Histoplasma
  • Cerebral spinal fluid (CSF) stain and culture
  • Serum Histoplasma antigen
Cryptococcus
  • India ink
  • Serum Cryptococcus antigen
  • CSF Cryptococcus antigen
  • Culture

Candida

  • Culture
  • Fungal stain
  • (1-3) beta-D-glucan

Coccidioides

  • CSF stain and culture
  • CF, ID, and ELISA antibodies
Blastomyces
  • CSF stain and culture
  • CF and ID antibodies, EIA
Trichosporon or Rhodotorula

N/A

Ophthalmologic
Ophthalmologic
Histoplasma
  • Culture
  • Serum Histoplasma antigen and antibody
Cryptococcus
  • Culture
  • Serum Cryptococcus antigen

Candida

  • Culture (vitreous fluid)
  • Blood culture
  • (1-3) beta-D-glucan

Coccidioides

N/A

Blastomyces

N/A

Trichosporon or Rhodotorula

N/A

Otorhinolaryngologic
Otorhinolaryngologic
Histoplasma

N/A

Cryptococcus
  • Fungal stain
  • Serum Cryptococcus antigen
  • Culture

Candida

  • Culture
  • Fungal stain

Coccidioides

N/A

Blastomyces

N/A

Trichosporon or Rhodotorula

N/A

Hepatosplenic or gastrointestinal
Hepatosplenic or Gastrointestinal
Histoplasma
  • Serum Histoplasma antigen
Cryptococcus
  • Blood culture
  • Serum Cryptococcus antigen
  • Tissue biopsy

Candida

  • (1-3) beta-D-glucan

Coccidioides

N/A

Blastomyces

N/A

Trichosporon or Rhodotorula

N/A

Dermatologic
Dermatologic
Histoplasma
  • Culture and histology of skin biopsy
  • Serum Histoplasma antigen
Cryptococcus
  • Culture of purulent material/fluid
  • Serum antigen

Candida

  • Fungal stain
  • Culture
  • Vaginal pathogens (DNA probe)

Coccidioides

  • Fungal stain of purulent material
  • CF, ID, and ELISA antibodies
Blastomyces
  • Fungal stain of purulent material
  • CF and ID antibodies, EIA
Trichosporon or Rhodotorula
  • Culture
Bone
Bone
Histoplasma
  • Bone marrow culture
  • Serum Histoplasma antigen
Cryptococcus
  • Bone marrow culture
  • Cryptococcus antigen

Candida

  • Bone marrow culture
  • (1-3) beta-D-glucan

Coccidioides

  • Bone marrow culture
  • CF, ID, and ELISA antibodies
Blastomyces
  • Bone marrow culture
  • CF and ID antibodies, EIA
Trichosporon or Rhodotorula

N/A

Genitourinary
Genitourinary
Histoplasma
  • Urine and serum Histoplasma antigen, and CF and ID antibodies
  • Tissue biopsy (focal lesion)
  • Disseminated disease – order fungal blood culture
Cryptococcus
  • Serum Cryptococcus antigen
  • Tissue biopsy (focal lesion)

Candida

  • Fungal stain
  • Culture
  • (1-3) beta-D-glucan

Coccidioides

N/A

Blastomyces
  • Urine culture after prostatic massage
  • CF and ID antibodies, EIA
  • Tissue biopsy (focal lesion)
Trichosporon or Rhodotorula
  • Urine culture (Trichosporon only)

Clinical Background

Yeasts cause a spectrum of diseases that range from colonization to uniformly fatal invasive disease.

  • Invasive fungal disease occurs in at-risk patient populations
    • Immunocompromised patients
    • Patients on immunomodulatory therapy
    • Patients with indwelling devices
    • Critically ill patients
  • Species most likely to cause disease include the following
    • Yeasts – Cryptococcus neoformans, Candida spp
      • Emerging infectious yeast agents such as Rhodotorula spp and Trichosporon spp
    • Dimorphic fungi – Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides immitis
    • See CDC for information on fungal diseases
  • Manifestations of infection may occur in one or more body sites
    • Often presents with symptoms related to site of involvement

Yeast-Associated Signs and Symptoms – Pulmonary

  • Risk factors for severe pneumonia and disseminated disease
    Risk Factors for Severe Pneumonia and Disseminated Disease
    Histoplasma
    • Young children
    • HIV
    Cryptococcus
    Candida
    • Renal failure
    • Presence of CVC/other vascular-access device
    • TPN administration
    Coccidioides
    • Pregnancy
    • HIV
    • Ethnicity
      • Filipino
      • Native American
      • African American
    Blastomyces
    • Pregnancy
    • Organ transplantation
    • HIV
    Trichosporon or Rhodotorula
    • Severely ill patients (eg, leukemia)
    Acute primary pulmonary infection
    Acute Primary Pulmonary Infection
    Histoplasma
    • Clinical picture similar to tuberculosis with fever, weight loss, and lymphadenopathy
    Cryptococcus
    • Fever
    • Chest pain
    • Cough
    • Sputum
    • Weight loss
    Candida
    • Fever
    • Sputum
    • Pneumonia (rare)
    Coccidioides
    • Clinical picture similar to tuberculosis with fever, weight loss, and lymphadenopathy
    Blastomyces
    Trichosporon or Rhodotorula

    N/A

    Chronic pulmonary disease
    Chronic Pulmonary Disease
    Histoplasma
    • Calcified nodes
    • Chronic cavitary disease
    • Mediastinal granuloma
    • Fibrosis
    Cryptococcus

    N/A

    CandidaN/A
    Coccidioides
    • Coin lesions (coccidiomas)
    • Cavitary disease (thin walled)
    • Granulomas
    Blastomyces
    Trichosporon or Rhodotorula

    N/A

Yeast-Associated Signs and Symptoms – Sites Other than Pulmonary

  • Ophthalmologic
    Ophthalmologic
    Histoplasma
    • Uveitis and panophthalmitis
    • Presumed ocular histoplasmosis syndrome 
      • Posterior uveitis with choroidal scars 
      • Neovascularization/loss of central vision
    Cryptococcus
    • Ocular palsies
    • Papilledema
    • Keratitis
    • Endophthalmitis
    Candida
    • Fungal keratitis
    • Endophthalmitis
    Coccidioides

    N/A

    BlastomycesN/A
    Trichosporon or Rhodotorula

    N/A

    Otorhinolaryngologic
    Otorhinolaryngologic
    Histoplasma

    N/A

    Cryptococcus
    • Gingivitis
    • Sinusitis
    • Salivary gland enlargement
    Candida
    • Thrush
    • Nasal ulcers
    • Otitis externa
    Coccidioides

    N/A

    BlastomycesN/A
    Trichosporon or Rhodotorula

    N/A

    Central nervous system
    Central Nervous System
    Histoplasma
    • Chronic meningitis
    • Cerebritis and mass lesion
    Cryptococcus
    Candida
    • Meningitis
    • Diffuse microabscesses in the brain
    Coccidioides
    • Chronic meningitis with indolent course
    Blastomyces
    • Abscesses
    • Meningitis
    Trichosporon or Rhodotorula

    N/A

    Hepatosplenic or gastrointestinal
    Hepatosplenic or Gastrointestinal
    Histoplasma
    • Hepatosplenomegaly
    • Chronic granulomatous hepatitis
    Cryptococcus
    • Disseminated yeast infections
      • Hepatitis 
      • Peritonitis 
      • Nodular/ulcerated lesions of colon
    Candida
    • Disseminated yeast infections
      • Esophagitis
      • Gastrointestinal ulcers
      • Peritonitis
      • Hepatic and splenic abscesses
    Coccidioides

    N/A

    Blastomyces

    N/A

    Trichosporon or Rhodotorula

    N/A

    Dermatologic
    Dermatologic
    Histoplasma

    Discrete erythematous skin papules in HIV patients

    Cryptococcus
    • Papules
    • Subcutaneous abscesses
    • Purpura
    • Bullae
    • Ulcers
    • Draining sinuses
    Candida
    • Folliculitis (generalized cutaneous form)
    • Disseminated skin infections
      • Intertrigo
      • Paronychia
      • Onychomycosis
      • Diaper rash
      • Vaginitis
      • Chronic mucocutaneous candidiasis
    Coccidioides
    • Maculopapular to verrucous lesions
    • Subcutaneous abscesses
    • Reactive eruptions (contain no organisms)
      • Erythema nodosum
      • Erythema multiforme
      • Toxic erythema
      • Sweet syndrome
    Blastomyces
    • Verrucous or ulcerative lesions
    • Subcutaneous nodules
    Trichosporon or Rhodotorula
    • Red papular lesions (T)
    • Catheter-related fungemia (R)
    Bone
    Bone
    Histoplasma
    Cryptococcus
    • Osteolytic lesions with soft-tissue abscesses

    Candida

    • Osteomyelitis (most common in spine, wrist, femur, ribs, scapula, and proximal humerus)
    • Arthritis

    Coccidioides

    • Osteomyelitis (most common in knees, hands, vertebrae, and long bones)
    • Symmetric arthritis (referred to as desert rheumatism)
    Blastomyces
    • Osteomyelitis (most common in long bones, vertebrae, and ribs)
    Trichosporon or Rhodotorula

    N/A

    Genitourinary
    Genitourinary
    Histoplasma
    • Epididymitis
    • Testicular and prostatic abscesses (rarely symptomatic)
    Cryptococcus
    • Prostatitis
    • Renal abscesses
    • Genital lesions

    Candida

    • Vulvovaginitis
    • Balanitis
    • Papillary necrosis
    • Fungus ball
    • Perinephric abscess

    Coccidioides

    N/A

    Blastomyces
    • Prostatitis
    • Epididymitis
    Trichosporon or Rhodotorula
    • Hematuria (T)
    • Funguria (T)

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Fungal Culture 0060149
Method: Culture/Identification

Gold standard for diagnosing fungal infection

Notify laboratory if Malassezia furfur is suspected

 
Fungal Stain, KOH with Calcofluor White 2004589
Method: Microscopy

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

Difficult to classify type of fungus from a smear

 
India Ink Stain 2004593
Method: Microscopy

Identify encapsulated yeast (eg, Cryptococcus)

   
Blood Culture, Fungal 0060070
Method: Continuous Monitoring Blood Culture/Identification

Gold standard for diagnosing fungi as agent of infection in blood

Wide range of reported sensitivity for yeast (40-90%)

 
Fungal Culture, Skin, Hair or Nails 0060728
Method: Culture/Identification

Gold standard for diagnosing fungi as agent of infection in skin, hair, or nails

   
Fungal (Mold/Yeast) Identification 0060163
Method: Identification. Methods may include biochemical, mass spectrometry, or sequencing.

Identify fungal agent responsible for infection

   
Histoplasma Antigen by EIA, Serum 0092522
Method: Semi-quantitative Enzyme Immunoassay

Diagnose and monitor response to therapy in Histoplasma-caused disease

Rarely positive in chronic disease

 
Histoplasma Galactomannan Antigen Quantitative by EIA, Urine 2009418
Method: Quantitative Enzyme Immunoassay

Diagnose and monitor response to therapy in Histoplasma-caused disease

   
Histoplasma capsulatum Identification by DNA Probe 0062226
Method: Nucleic Acid Probe

Rapid test for identifying H. capsulatum (yeast or mold form) from pure isolate

Chrysosporium anamorph Nannizziopsis vriesii may cross-react with H. capsulatum AccuProbe

 
Cryptococcus Antigen, Serum 0050196
Method: Semi-quantitative Enzyme Immunoassay

Confirm C. neoformans as infectious agent of invasive cryptococcal disease

   
Cryptococcus Antigen, CSF 0050195
Method: Semi-Quantitative Enzyme Immunoassay

Confirm C. neoformans as infectious agent of meningitis

   
(1,3)-Beta-D-Glucan (Fungitell) 2002434
Method: Semi-Quantitative Colorimetry

Aid in diagnosis of invasive Candida infections

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

Does not detect Zygomycetes (ie, Absidia, Mucor, and Rhizopus)

 
Vaginal Pathogen Panel by DNA Probe 0065153
Method: Qualitative Nucleic Acid Probe

Use to detect common vaginal pathogens associated with vaginitis/vaginosis

Not recommended as stand-alone test for sexually transmitted infection testing or screening

Includes testing for Candida species, Gardnerella vaginalis, and Trichomonas vaginalis

Sensitivity may vary with quality of specimen collection

For Trichomonas vaginalis, preferred test is one of the nucleic acid amplification tests (NAAT) (ie, Trichomonas vaginalis by Amplified Detection)

Poor clinical specificity; cannot distinguish colonization from active infection

 
Coccidioides Antibodies Panel, CSF by CF, ID, ELISA 0050710
Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Confirm coccidioidal disease as infectious agent in meningitis

   
Coccidioides Antibodies Panel, Serum by CF, ID, ELISA 0050588
Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Confirm coccidioidal disease as infectious agent

Use to monitor response to therapy

Negative fungal serology does not rule out possibility of current infection

 
Coccidioides immitis Identification by DNA Probe 0062225
Method: Nucleic Acid Probe

Rapid test for identifying C. immitis (yeast or mold form)

   
Blastomyces dermatitidis Identification by DNA Probe 0062224
Method: Nucleic Acid Probe

Rapid test for identifying B. dermatitidis (yeast or mold form)

Gymmascella hyalinospora, a member of the Ascomycetes order, may cross-react with B. dermatitidis probes

 
Blastomyces dermatitidis Antigen EIA 2002926
Method: Quantitative Enzyme Immunoassay

Diagnose and monitor B. dermatitidis

   
Blastomyces Antibodies by CF and ID 0050626
Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion

Confirm Blastomyces as infectious agent

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Coccidioides Antibodies, IgG & IgM by ELISA 0050137
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Fungal Antibodies by Immunodiffusion 0050164
Method: Qualitative Immunodiffusion
Fungal Antibodies by CF, Serum 0050605
Method: Semi-Quantitative Complement Fixation
Fungal Identification by ITS rDNA Sequencing 0060756
Method: Sequencing

Identify clinically significant isolates

Antimicrobial Susceptibility - Fungal (Yeasts and Molds) 2009257
Method: Broth Microdilution

Determine minimum inhibitory antifungal agent concentration to treat identified Candida, Cryptococcus, Geotrichum, and Trichosporon species

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

Blastomyces Antibody by CF 0050130
Method: Semi-Quantitative Complement Fixation

Use with paired sera taken 3 weeks apart to detect a rise in titer against a single antigen

Blastomyces dermatitidis Antibodies by Immunodiffusion 0050172
Method: Qualitative Immunodiffusion

Measure IgG antibodies

Candida Antibody by ID 0055565
Method: Qualitative Immunodiffusion
Candida albicans Antibodies IgA, IgG, and IgM by ELISA 0095200
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Measure IgG, IgM and IgA antibodies

Best evidence for infection is significant change on two 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

Coccidioides Antigen by EIA 2011075
Method: Quantitative Enzyme Immunoassay
Coccidioides Antibody by CF 0050170
Method: Semi-Quantitative Complement Fixation

Detect current or past infection

Monitor response to therapy

Least sensitive in pulmonary cavitary disease

Coccidioides immitis Antibodies by Immunodiffusion 0050183
Method: Qualitative Immunodiffusion

Detect current or past infection

Monitor response to therapy

Coccidioides Antibody, IgG by ELISA 0050179
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Detect current or past infection

Negative fungal serology does not rule out possibility of current infection

Coccidioides Antibody, IgM by ELISA 0050178
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Detect current or past infection

Negative fungal serology does not rule out possibility of current infection

For equivocal results, repeat test in 10-14 days 

Histoplasma Antibodies by CF 0050625
Method: Semi-Quantitative Complement Fixation

Detect current or past Histoplasma infection

Histoplasma Antibodies by CF & ID 0050627
Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion

Detect current or past Histoplasma infection

Negative fungal serology does not rule out possibility of current infection

Histoplasma spp. Antibodies by Immunodiffusion 0050174
Method: Qualitative Immunodiffusion

Identify Histoplasma as causative agent in disease

Negative fungal serology does not rule out possibility of current infection

Fungal Antibodies by CF, CSF 0050750
Method: Semi-Quantitative Complement Fixation