Opportunistic Mycoses - Microbiology

Snapshot

A 40-year-old woman presents to the emergency room with a week of fever, cough, and hemoptysis. She has a history of HIV and has been noncompliant with her medications and has a history of tuberculosis that was adequately treated. She reports feeling increasing fatigue. A chest CT shows nodules with a halo sign. A bronchoalveolar lavage with biopsy eventually reveals fungus with septate hyphae branching at acute angles invading into lung tissue. (Invasive aspergillosis)

Candida albicans

Classification
- yeast with budding and pseudohyphae
- germ tube formation at 37°C (diagnostic)
- can be part of normal flora
Risk factors
- immunocompromised status
- hospital admission, especially in the ICU
Clinical syndrome
- immunocompetent hosts present with skin and mucous membrane infections
  - oral thrush
    - white plaque on the tongue that can be scraped off
  - candidal intertrigo
    - well-demarcated, erythematous, and itchy plaques in the skin folds
  - vulvovaginitis
    - thick "cottage cheese" white discharge
    - itchiness
- immunocompromised hosts usually present with systemic disease
  - local infection is due to T-cell deficiency while systemic infection is due to neutropenia
  - esophagitis
    - dysphagia and throat pain
    - endoscopy shows white plaques along the esophagus
  - endocarditis
    - associated with IV drug users
    - fevers and a new murmur
  - disseminated/invasive candidiasis
    - fever and septic shock
Studies
- definitive diagnosis requires blood or other tissue culture
- wet mount with potassium hydroxide prep of vaginal fluid shows yeast with pseudohyphae
- germ tube formation at 37°C
Treatment
- nystatin
  - local infections
- azoles
  - local and systemic infections
  - first-line if the fungus is not resistant
- echinocandins
  - systemic infections
  - first-line due to increased resistance to azoles
- amphotericin B
  - systemic infections
  - second-line or for pregnant women

Cryptococcus neoformans

Classification
- urease-positive monomorphic encapsulated yeast with 5-10 μm narrow budding
- transmitted via inhalation and found in soil and pigeon droppings
Risk factors
- immunocompromised status
- HIV/AIDS patients
Clinical syndrome
- cryptococcosis
- cryptococcal meningitis
- cryptococcal encephalitis
- presents with fevers, headaches, and generalized malaise
Studies and imaging
- head imaging with computed tomography (CT) or magnetic resonance imaging (MRI)
  - soap bubble lesions
  - variable enhancing lesions
  - hydrocephalus
- detection of capsular antigen in serum or cerebrospinal fluid (CSF)
  - latex agglutination test
- CSF studies
  - culture on Sabouraud agar
  - India ink stain shows yeast with clear halos
  - mucicarmine shows yeast with red inner capsules
Treatment
- amphotericin B + flucytosine
  - for 10-14 days
- fluconazole
  - after treatment with amphotericin B and flucytosine
  - maintenance and suppressive therapy

Aspergillus spp.

Classification
- most commonly Aspergillus fumigatus
- monomorphic fungus with septate hyphae branching at acute angles (45 degrees)
- found in soil and decomposed material
- transmission via inhalation of spores
Risk factors
- immunocompromised status
- hematologic malignancy
- asthma
- pre-existing lung disease
Clinical syndrome
- invasive aspergillosis
  - invasive infection of the lung
  - causes persistent fever and cough with hemoptysis
- aspergilloma
  - mycetoma ("fungal ball") in pre-existing cavity (i.e., tuberculosis)
  - causes cough with hemoptysis or asymptomatic
- allergic bronchopulmonary aspergillosis (ABPA)
  - hypersensitivity reaction in patients with cystic fibrosis or asthma
  - causes bronchiectasis and eosinophilia
  - causes cough with hemoptysis, brownish black mucus plugs in expectorate, and wheezing
Studies and imaging
- invasive aspergillosis
  - nodules with halo sign and cavitary lesions on computed tomography (CT)
  - pathologic examination showing invasive hyphae into tissue
  - positive cultures or serology
- aspergilloma
  - mobile round or ovoid mass on chest CT
  - positive cultures or serology
- ABPA
  - bronchiectasis on CT
  - elevated eosinophils or IgE in ABPA
Treatment
- invasive aspergilloma
  - voriconazole + amphotericin B
    - first-line
  - caspofungin
    - second-line
- aspergilloma
  - surgical resection
- ABPA
  - steroids
    - first-line

Mucormycosis

Classification
- Mucor and Rhizopus spp.
  - fungi with irregular, broad, and nonseptate hyphae branching at wide or right angles
  - found in soil and decomposed material
  - transmission via inhalation of spores or direct inoculation through trauma
Risk factors
- diabetic ketoacidosis
- immunocompromised status
- trauma or burns
Clinical syndrome
- mucormycosis (rhinocerebral infection)
  - headache
  - congestion
  - sinus pressure and pain
  - black necrotic eschar on face, particular nares or palate
Studies and imaging
- computed tomography (CT) shows air-fluid levels in the sinuses and bony destruction
- biopsy of affected tissue shows nonseptate hyphae with wide-angle branching
Treatment
- amphotericin B
  - first-line
- isavuconazole
  - second-line
- surgical debridement
  - for patients who need it, in addition to antifungals

Pneumocystis jiroveci

Classification
- a yeast-like fungus
- transmission via airborne
Risk factors
- immunocompromised status (e.g., hyper IgM syndrome)
- HIV
- smoking
Clinical syndrome
- interstitial pneumonia
  - progressive exertional dyspnea
  - chest pain
  - nonproductive cough
  - fever and chills
  - hemoptysis is rare
Imaging
- chest radiograph will show bilateral infiltrates
- computed tomography will show patchy ground-glass opacities sand pneumatoceles
Studies
- histology with methenamine silver, Diff-Quik, or Wright stain of lung tissue
  - disc-shaped yeast
Treatment
- trimethoprim-sulfamethoxazole (TMP-SMX)
  - prophylaxis (CD4+ count < 200 cells/mm³) and first-line therapy
- corticosteroids
  - severe cases
- pentamidine, atovaquone, or dapsone
  - second-line therapy if resistant to TMP-SMX or allergic

Blood, Plasma, Serum	Reference Range
ALT	8-20 U/L
Amylase, serum	25-125 U/L
AST	8-20 U/L
Bilirubin, serum (adult) Total // Direct	0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca²⁺)	8.4-10.2 mg/dL
Cholesterol, serum	Rec: < 200 mg/dL
Cortisol, serum	0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h
Creatine kinase, serum	Male: 25-90 U/L Female: 10-70 U/L
Creatinine, serum	0.6-1.2 mg/dL
Electrolytes, serum
Sodium (Na⁺)	136-145 mEq/L
Chloride (Cl^-)	95-105 mEq/L
Potassium (K⁺)	3.5-5.0 mEq/L
Bicarbonate (HCO₃^-)	22-28 mEq/L
Magnesium (Mg²⁺)	1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)
24-28 wks // 32-36 wks	30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks	40-220 ng/mL // 80-350 ng/mL
Ferritin, serum	Male: 15-200 ng/mL Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma	Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250
pH	7.35-7.45
PCO₂	33-45 mmHg
PO₂	75-105 mmHg
Glucose, serum	Fasting: 70-110 mg/dL 2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation	Fasting: <5 ng/mL Provocative stimuli: > 7ng/mL
Immunoglobulins, serum
IgA	76-390 mg/dL
IgE	0-380 IU/mL
IgG	650-1500 mg/dL
IgM	40-345 mg/dL
Iron	50-170 μg/dL
Lactate dehydrogenase, serum	45-90 U/L
Luteinizing hormone, serum/plasma	Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL
Osmolality, serum	275-295 mOsmol/kd H₂O
Parathyroid hormone, serume, N-terminal	230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C)	20-70 U/L
Phosphorus (inorganic), serum	3.0-4.5 mg/dL
Prolactin, serum (hPRL)	< 20 ng/mL
Proteins, serum

Hematologic	Reference Range
Bleeding time	2-7 minutes
Erythrocyte count	Male: 4.3-5.9 million/mm³ Female: 3.5-5.5 million mm³
Erythrocyte sedimentation rate (Westergren)	Male: 0-15 mm/h Female: 0-20 mm/h
Hematocrit	Male: 41%-53% Female: 36%-46%
Hemoglobin A1c	≤ 6 %
Hemoglobin, blood	Male: 13.5-17.5 g/dL Female: 12.0-16.0 g/dL
Hemoglobin, plasma	1-4 mg/dL
Leukocyte count and differential
Leukocyte count	4,500-11,000/mm³
Segmented neutrophils	54%-62%
Bands	3%-5%
Eosinophils	1%-3%
Basophils	0%-0.75%
Lymphocytes	25%-33%
Monocytes	3%-7%
Mean corpuscular hemoglobin	25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration	31%-36% Hb/cell
Mean corpuscular volume	80-100 μm³
Partial thromboplastin time (activated)	25-40 seconds
Platelet count	150,000-400,000/mm³
Prothrombin time	11-15 seconds
Reticulocyte count	0.5%-1.5% of red cells
Thrombin time	< 2 seconds deviation from control
Volume
Plasma	Male: 25-43 mL/kg Female: 28-45 mL/kg
Red cell	Male: 20-36 mL/kg Female: 19-31 mL/kg

Cerebrospinal Fluid	Reference Range
Cell count	0-5/mm³
Chloride	118-132 mEq/L
Gamma globulin	3%-12% total proteins
Glucose	40-70 mg/dL
Pressure	70-180 mm H₂O
Proteins, total	< 40 mg/dL

Sweat	Reference Range
Chloride	0-35 mmol/L
Urine
Calcium	100-300 mg/24 h
Chloride	Varies with intake
Creatinine clearance	Male: 97-137 mL/min Female: 88-128 mL/min
Estriol, total (in pregnancy)
30 wks	6-18 mg/24 h
35 wks	9-28 mg/24 h
40 wks	13-42 mg/24 h
17-Hydroxycorticosteroids	Male: 3.0-10.0 mg/24 h Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total	Male: 8-20 mg/24 h Female: 6-15 mg/24 h
Osmolality	50-1400 mOsmol/kg H₂O
Oxalate	8-40 μg/mL
Potassium	Varies with diet
Proteins, total	< 150 mg/24 h
Sodium	Varies with diet
Uric acid	Varies with diet
Body Mass Index (BMI)	Adult: 19-25 kg/m²