Mycology I Flashcards
Most important opportunistic fungi
Cryptococcus Candida Aspergillus Mucorales Pneumocystis jirovecii Black moulds (Pheohyphomyces)
Cryptococcosis Epidemiology
Etiology: C. neoformans, C. gattii
Ecology
-Neoformans: worldwide, birds, soil; human infection NOT assd with bird/koala contact
-Gattii- less widely distributed/arboreal; –eucalyptus trees in Australia, tropical/subtropical Africa, Asia, Hawaii
Cryptococcosis Mycology/virulence
Yeast
- grows on conventional media: creamy, undistinctive colony
- Micro: round-oval thin-walled yeast usually with polysaccharide capsule that can be larger than parent cell. Buds attached by NARROW-based
VIRULENCE
1) polysaccharide Capsule- inhibit phag (evade macs for pulmonary dz and monocyte/PMNs for disseminated)
2) Produces melanin via phenol oxidase to protect from oxidative stress – need for dz. may explain why they like brain (high levels of daopamine = melanin precursor)
HOST factors
- neoformans: opportunistic but occasionally normal host get pulm dz: AIDS, prolonged glucocorticoids, solid-organ transplant, malignancy (esp lymphomas), sarcoid (NB: Conditions with impaired CELLULAR IMMUNITY
- C. gatii: equal dz in immune comp and nl hosts
- rare in kids
Cryptococcus dz
- Enter via inhalation
- MENINGITIS = KEY SYNDROME: hemotogenous spread (typically from inapparent lung focus); HIV; major mortality esp in Sub-Saharan Africa; NONINFLAMMATORY–many orgs but few phagocytic cells. 100% mortality without treatment, 15% if treated in resource-rich country
- isolated pulmonary cryptococcosis: usu. asymp. form granuloma–growth can be seen as nodular infiltrate in CXR
- skin/soft tissue (disseminated cryptococcosis)
- -much less common; other sites: kidney, bone joint,
- can be asymptomatic or cause cryptogenic fevers in IC hosts
DIAGNOSE:
- CRAG= cryptococcal antigen test detecting capsule = TEST OF CHOICE (very sensitive/specific/cheap/fast)
- 3 types of tests: immunocromographic lateral flow assay (LFA), Enzyme immunoassay (EIA), older latex slide agglutination (LA) (LFA easier/more sensitive but more expensive)
- INDIA INK highlights capsule but now replaced by CRAG
MICRO:
- Gram stain highlights org/capsule
- routine agar growth in 24 hrs (blood/csf/tissue biopsy)
- confirmatory tests: Rapid urea production, reduction fo nitrate to nitrite, melanin producgion on BIRD SEED AGAR)
- C. Gatii vs neoformans: Gatii turns blue on CGB agar
- Mucicarmine stains capsule pink since yeast not visible on H&E
Cryptococcos neoformans KEY FA FACTS
- meningitis, cryptococcosis
- heavily encapsulated YEAST –NOT dimorphic
- soil/pigeon dropings
- inhalation w/heme spread to meninges
- Sabouraud agar/ India ink stain or mucicarmine
- “latex agglutination test to detect capsule
- “SOAP BUBBLE LESIONS” with thick capsule
- Treat: Amphotericin + flucytosine followed by fluconazole for maintenence
Treat Cryptococcosis
Meningitis/disseminated:
- Induction (lipid based) amphotericin B + 5 flycytosine then maintenance with fluconazole
- Isolated pulm dz: fluconazole
Invasive candidiasis
- many species but mainly C. albians, C parapsilosis, C, glabrata
- ubiquitous; nl comensal/ colonization of ucosal surfaces at birth. Invasive dz primarily from MEDICAL PROGRESS
- small, ovoid yeast w/ frequent budding; growth on routine media for bacteria and fungal media. Creamy undistinctive colony
- Albicans = GERM TUBE POSITIVE (at 27 deg C) vs pseudohyphae & budding yeast at 22 deg.
VIRULENCE:
- nl in GI; when bacterial flora/host defenses diminished, can invade mucosal surface to get to blood
- can be polymicrobial infection – intraabdominal (cholecystitis, pancreatitis, UTI, etc)
- adhere to indwelling devices
HOST FACTORS
- Invasive care (TPN, IV catheters)
- Immune compromised, premature babies, neutropenia, chemo, SOT, SCT
DZ:
- Fever + Leukocytosis. skin papules/nodules clue to disseminated infection
- 3 main INVASIVE dz syndromes
1) CANDIDEMIA: indwelling catheters
2) CANDIDEMIA + Visceral dz (EYE, kidney, brain, lung, skin
3) Isolated visceral (w/o detection in blood) - Endoohthalmitis
- Endocarditis (IVDU, indwelling catheters)
- TUI ( distinguish from bladder colonization; from ascending infection or heme spread)
Candida diagnosis/Treat
- Direct microscopy– see yeast on gram stain, KOH prep, calcofluour white, and others. Some form pseudohyphae and/or true hyphae
- Culture- 1-5 days from blood, 1-2 for other specimens
- Histo: Yeast cells, some hyphae and/or pseudohyphae. If not neutropenic than microabscesses seen. Granulomatous reaction NOT typical
- BETA-D-glucan antigen test: present in most fungal cell walls. Sensitive but not specific to candida so best when applied to select high-risk pts
Treat:
- Echinocandins = first line (2016) **check susceptibility to guide treatment
- Fluconazole/other azonles often good for eyes
- Amphotericin B+/- 5-flucytosine may be used for severe dz
Candida FA facts
Infections
- Oral/esophageal thrush– white stuff can be scraped off
- vulvovaginitis (diabetics, antibiotics)
- diaper rash
- endocarditis (IVDU)
- Disseminated (to any organ)
- Chronic mucocutaneous candidiasis
Treat:
Vaginal: topical azole
Oral/esophageal: nystatin (swish in mouth), fluconazole, caspofungin
Systemic: Fluconazole, caspofungin or amphotericin B
-Catalase +, so think about in chronic granulomatous dz!!
Aspergillus
Most by 4 species (fumigatus, flavus, terreus, niger)
- majority = A. fumigatus
- ubiquitous/worldwide in air/soil. decaying vegetables; typically likes moist environments
- septae hyphae; rapid growth with fuzzy velvety texture
- hyphae - clear and must sporulate for identification; spore + conida (shape helps with species ID)
Pathogenisis
- Inhale and adheres to mucosa or lodges in areas of resp tract w/o nl ciliary clearance
- *OLD TB CAVITIES or abnl lungs
- IC hosts: hyphae invades nl tissue, esp angioinvasive. Causes ischemic NECROSIS, clot formation, INFARCTION. PMNS key to host defense but sudden cell increase can lead to sudden and fatal bleeding
HOST factors
- Neutropenia (heme malignancies), p rolonged glucocorticoids, SOT, SCT, advanced HIV, CGD
- chronic local dz in nl hosts with abnormal lung (COPD, old cavitary dz)
Aspergillus Dz
2 main pulmonary forms
(NOTE: allergic bronchopulmonary aspergillosis (ABPA) NOT infection but allergic rxn to aspergillus in airway or environment.)
1) Chronic aspergillosis (aspergilloma, chronic necrotizing pneumonia, cavitary dz, etc) - seen in nl hosts. can be asymp or constitutional sxs, hemoptysis from inflammation. Hard to distinguish from malignancy, TB other invasive fungal dz
2) acute invasive aspergillosis (IC hosts)
- fever, abnl CXR/CT (peripheral wedge-shaped infarction, rapidly expanding nodules, rapid cavitation)
- disseminated results from spread in blood from pulmonary invasive dz. 2nd to candida as fungal cause of death in hematologic malignancies and SCT. Lungs, brain, kidney, skin
3) Cutaneous aspergillosis (Usually IC hosts)
- primary inoculation such as IV site, skin abrasion, under tape/dressing. Skin nodules also seen with disseminated dz)
4) Sino-orbital aspergillosis
- can be identical to mucormycosis but in neutropenic hosts NOT diabetics
Aspergillus: Diagnosis
- Direct microscopy- doesn’t gram stain well; narrow hyphae, septate, 45 deg angle
- angioinvasion/necrosis
Serologic tests:
- Aspergillus galactomannan antigen (polysaccharide in cell wall)– can detect other fungal dz
- beta-D glucan Ag test: same as candida (not specific)
- Aspergillus Ab detection aka “aspergillus precipitans” (not good for invasive dz)
Treat: combined med/surgical superior to medical alone (but surgical not always possible)
- Voriconazole, posaconazole, isavuconazole, amphotericine B, echinocandins all have activity
Mucormycosis
Rhizopus, Mucor, Rhizomucor
- ubiquitous; common bread mold, decaying matter
Rapid growth, wooly, white colony pigmented with age
- Broad ribbon-like hyphae with 90 degree branching. Spores within sporangium with root-like extensions
- Iron enhances growth
- Rhizopus has ketone reductase– growth stimulated in high glucose/acid
Patho:
- spores inhaled/attach to mucosa. rapid growth once in tissue; angioinvasive so see necrosis/infarction
HOST
- Diabetes esp KETOACIDOSIS, treatment with deferoxamine, Fe overload, IVDU, traumatic inoculation/burns, IMPAIRED CELLULAR IMMUNITY (glucocorticoids, heme malignancy, SOT (esp liver transplant), SCT
Mucor clinical features/diagnosis/treat
- PROGRESSES FAST (within hours)
1) Rhinocerebral mucormycosis (necrotic ulcer on palate followed by orbital invasion, extensiont o cavernous sinus/brain)
2) pulmonary mucormycosis: variable presentation based on immune fxn. Can progress slowly in nl host vs fast in IC hosts
3) cutaneous mucormycosis- contaminated wounds, combat, IVDU, burns, under bandages
Diagnose
- clinical presentation
- culture without biopsy not diagnostic since often airborne contaminants
- biopsy: braod hyphae often irregular thickness, usually non-septae, right angle branching w/predilection of blood vessel invasion
Treat:
- Rhinocerebral mucormycosis = MED/SURG EMERGENCY
- Combined Med/Surg»_space; medical
- –invasive dz: need debridement,; delay results in more involvement/inability to obtain surgical control
- Liposomal amphotericin B only fungicidal drug
- Posaconazole and isavuconazole have activity
Pneumocystis Pneumonia (PCP)
- Pneumocystis jirovecii (lacks ergosterol)
- worldwide; most develop Ab during childhood
- 3 stages: trophozoite, pre-cyst, thick walled cyst with up to 8 intracystic bodies
- ALMOST ALWAYS IN PTS w/ DEFECTIVE CELLULAR IMMUNITY (AIDS, SCT, SOT, immune modulators, Prolonged glucocorticoids, ALL, lymphopenia/malnutrition)
- Dyspnea, fever, nonprod. cough, variable tachypnea, tachycardia, cyanosis
- CXR: “DIFFUSE PERIHILAR RETICULONODULAR INFILTRATES”
DIAGNOSIS
- Microscopy: direct fluorescent antibody stains trophs and cysts (PCP DFA)
- NOT recovered in culture
- PCR (so sensitive can pick up transient colonization)
- Histopathology: trphs stain with Pap & Giemsa stain. Cysts stained with GMS.
- *Small, nonbudding yeasts, similar to candida
Treat:
- TPM-SMX inhibits = Treatment of choice
- Alt: Trimethoprim + Dapsone, clindamycin + Primaquine, atovaquone, pentamidine, trimetrexate
