Opportunistic Mycoses

Question 1

Candidiasis

Answer 1

Most commonly encountered
Involve any anatomical structure (ability to gain access to circulation and deep tissues iatrogenic mechanism)
Increase risk: critically ill, medical and surgical ICUs

Question 2

Candidiasis morphological features

Answer 2

Budding yeast + pseudohyphae + true hyphae + germ tube

Question 3

Candidiasis pathogenicity

Answer 3

Human and animal reservoir
Recovered from environment, especially hospitals
Initial step is colonization of a mucocutaneous surface
- disruption of surface allows access to blood stream
- persorption via GI wall allowing direct passage into bloodstream

Question 4

Candidiasis risk factors

Answer 4

Pregnancy, elderly, infancy
Burn, infection
Cellular immune deficiency, AIDS, chronic granulomatous disease, aplastic anemia, leukemia, lymphoma
DM, hypoparathyroidism, Addison disease
Oral contraceptives, antibiotics, steroid, chemotherapy, catheter

Question 5

Candidiasis morbidity and mortality

Answer 5

Mucocutaneous:
Most candidiasis infections, never fatal in healthy individuals
Severe oropharyngeal and esophageal candidiasis in AIDS pts (poor oral intake, malnutrition, wasting followed by death
Candied Mia and disseminated candidiasis
30-40% mortality
Hospitalized pts
Uncommon in AIDS pts

Question 6

Candidiasis clinical presentation

Answer 6

Cutaneous and subcutaneous: oral, vaginal, onychomycosis, dermatitis, diaper rash, balanitis
Systemic: esophagitis, pulmonary infection, cystitis, pyelonephritis, endocarditis, myocarditis, peritonitis, hepatosplenic, endophthalmitis, arthritis, osteomyelitis, meningitis, skin lesions
Cottage cheese appearance, white or yellow color
Chronic mucocutaneous: skin and mucous membranes, verrucous lesions, impaired cellular immunity, autosomal recessive trait, hypoparathyroidism, iron deficiency

Question 7

Candidiasis diagnosis

Answer 7

Direct microscopic examination: yeast cells, pseudohyphae, true hyphae, germ tube
Culture: differentiation of species on CHROMagar, isolation of organism for subsequent species identification
Serology: Candida mannan assay

Question 8

Candidiasis treatment

Answer 8

Cutaneous/mucocutaneous: topical antifungals Ketoconazole, Miconazole, Nystatin
Systemic: Amphotericin B, Fluconazole, Itraconazole
Chronic mucocutaneous: Amphotericin B, Fluconazole, Itraconazole

Question 9

Cryptococcosis

Answer 9

C. neoformans: US and other temperate climates, found in soil and aged pigeon droppings
C. gattii: tropical and subtropical areas, associated with eucalyptus tree
Crucial factor is immune state, defective CMI
Inhalation, transplantation in organ transplants

Question 10

Cryptococcosis pathogenesis

Answer 10

Transmitted by resp inhalation
Yeast spores deposited into pulmonary alveoli
Phagocytized by alveolar macrophage, capsule has antiphagocytic properties and maybe immunosuppressive

Question 11

Crypptococcosis clinical presentation

Answer 11

Pulmonary: asymptomatic, flulike illness, or fulminant bilateral PNA
Disseminated: meningitis (severe in immunocompromised individuals, and most common cause of meningitis in immunocompromised), cryptococcoma (most common CNS presentation in immunocompetent), skin lesions

Question 12

Cryptococcosis diagnosis

Answer 12

Direct microscopic examination:
CSF, sputum, aspiration from skin lesion
Detection of encapsulated budding yeast
*India ink stain with CSF*
Culture
Serology:
Detection of capsule Ag in CSF and serum by latex agglutination test

Question 13

Cryptococcosis treatment

Answer 13

Anti-fungal therapy for meningitis and disseminated disease
Follow up critical, examination of CSF
Amphotericin B (+ Flucytosine)
Life-long fluconazole prophylaxis following primary treatment in AIDS pts with CD4 count below 50

Question 14

Aspergillosis

Answer 14

Found in air, soil, decaying matter
Most common is A. fumigatus
Risk factors: almost always in immunosuppressed (underlying lung disease, immunosuppressive drug therapy, immunodeficiency, co-morbidities such as COPD asthma CF)

Question 15

Aspergillosis clinical presentation

Answer 15

Allergic bronchopulmonary aspergillosis (ABPA): hypersensitivity reaction to colonization of tracheobronchial tree, occurs in conjunction with asthma and CF

Chronic necrotizing aspergillus PNA/ pulmonary aspergillosis (CNPA): subacute infection (such as recovery from TB), individual exhibits some degree of immunosuppression (lying disease, alcoholism, or long term corticosteroid therapy), progressive cavity pulmonary infiltrate

Aspergilloma: development of fungus ball (mycetoma) in preexisiting cavity in lung parenchyma, cavitary disease commonly result of TB sarcoidosis CF and emphysematous bullae, does not invade cavity wall, can cause hemoptysis

Invasive aspergillosis: rapidly progressive, often fatal infection in pts who are severely immunosuppressed or have had prolonged neutropenia, fever cough dyspnea pleurtic chest pain and sometimes hemoptysis, dissemination to other organs including CNS

Question 16

Aspergillosis diagnosis

Answer 16

Direct microscopic examination:
Sputum, bronchoaveolar lavage, tissue
Septae hyphae and conidia in sputum, intravascular hyphae in tissue
Histopathology:
Septate hyphae that branches at ACUTE ANGLES
Culture:
Grow in absence of cycloheximide
Observation of spherical conidia, vesicles and phialides
Serology:
Rapid diagnosis of invasive aspergillosis
Enzyme immunoassay for aspergillus galactomannan Ag in serum

Question 17

Aspergillosis treatment

Answer 17

ABPA: oral steroids
Aspergilloma: surgical resection, intraccavity treatment with Amphotericin B
CNPA: anti-fungal treatment until radiographic resolution, surgical resection if anti-fungal fail
Invasive aspergillosis (high mortality rate): surgical debridement, anti-fungal therapy (Amphotericin B, Itraconazole), decrease level of immunosuppression, filter air

Question 18

Pneumocystis jiroveci Pneumonia

Answer 18

Most common in HIV pts at CD4 count at 200

Question 19

PJP clinical presentations

Answer 19

Symptoms are nonspecific, flulike symptoms
With HIV more subacute indolent course and tends to present much later after several weeks of symptoms: exertional dyspnea, fever, nonproductive cough, chest discomfort, wt loss, chills, hemoptysis (rare)
Additional findings in children with severe disease include cyanosis, nasal flaring, and intercostal retractions (resembles RSV)

Question 20

PJP pathophysiology

Answer 20

Pneumocystis attaches to and kills Type I pneumocystis and type II becomes overly abundant and damages alveolar epithelium
Serum leaks into alveoli, producing exudate with foamy/honeycomb appearance on H&E stain
Silver stain reveals holes in the exudate actually the cysts and trophozoites, which do not stain with H&E
X-ray: patchy infiltrate (ground glass appearance), the lower lobe periphery

Question 21

PJP diagnosis

Answer 21

Silver staining cysts in bronchial alveolar lavage fluids or biopsy
A lactic dehydrogenase study is performed as part of initial workup, usually elevated in PJP

Question 22

PJP treatment

Answer 22

DOES NOT respond to antifungal treatment

TMP-SMX
Second line: pentaminidine or dapsone + pyrimethamine

Capsofungin? Activity against beta-D glucan

Question 23

Mucormycosis

Answer 23

Aka: Zygomycosis
Rhizopus most common
Highly ubiquitous, high levels of exposure, low virulence
Natural reservoir: air water soil
Most infections fatal
Risk factors: diabetic ketoacidosis, neutropenia and immunosuppression

Question 24

Mucormycosis pathogenesis

Answer 24

Primary route is inhalation of sporangiospores: ingestion and traumatic inoculation, infections that start in nose and mouth

Mucoraceae are molds in environment and take on hyphal form in tissue

As spores grow, hyphae invade blood vessels -> production of infarction, necrosis, and thrombosis -> apt to spread to brain quickly

Question 25

Mucormycosis clinical presentation

Answer 25

Rhinocerebral: progressive orbital swelling and facial cellulitis, discharge of black pus
Proptosis, ptosis, chemosis, and opthalmoplegias: involvement of cranial nerves V and VII, power entail loss of vision
Reduced conscious state: indicative of brain involvement
Differential: anthrax
Cutaneous: progressive black necrotic lesion, result of vessel invasion (characteristic of all forms of disease)
Pulmonary: nonspecific fever dyspnea and cough, individuals with malignancies and history of neutropenia
GI: nonspecific abdominal pain distension n/v, affect severely malnourished
CNS: ha, decreasing consciousness, and focal neurological symptoms (CN deficits), history of open head trauma drug use or malginancy

Question 26

Mucormycosis diagnosis

Answer 26

Dependent of histologic findings of a biopsy of necrotic tissue
- broad based, ribbon like, nonseptate hyphae with RIGHT ANGLE BRANCHING

Culture:
Cotton candy appearance, characteristic feature of Rhizopus species (sporangium, rhizoids)

Question 27

Mucormycosis Treatment

Answer 27

Antifungal: Amphotericin B
Surgical debridement
Immune reconstitution

High mortality rate

Question 28

Fungemia

Answer 28

Malassezia furfur
Nosocomial infections directly related to administration of IV lipid supplements through central venous catheter
Infection subsides once lipid infusion stopped and line removed

Trichosporon species
Catheter associated in neutropenia pts (individuals with malignancies)
Antifungal therapy usually inefficient (80% mortality)