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35 Cards in this Set
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Invasive fungal infection
Filamentous fungi (moulds) Yeast Dimorphic fungi |
Invasive fungal infections (deep fungal infections or deep mycoses)→Infections that involve internal organs (skin +/- involved)
Filamentous fungi (moulds)→Grow as multinucleate, branching hyphae, forming a mycelium; undergo asexual reproduction Yeast→Grow as ovoid or spherical single cells that multiply by budding & division Dimorphic fungi→Form hyphae at environmental temperatures but grow as yeast in the body |
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Invasive fungal infection acquisition
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Many of the fungi that cause human disease are free-living organisms in the environment (e.g. Aspergillus) that may be acquired by inhalation, ingestion, or inoculation thru the skin; certain of these fungi have a very restricted geographic endemicity (e.g. Coccidioides)→Exogenous in origin
Some fungal pathogens are part of the normal human flora (e.g. Candida) & invade when host defenses become impaired→Endogenous in origin Human to human transmission is uncommon |
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Invasive fungal infections incidence
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Population of pts at risk for IFIs has expanded dramatically over past 20+ yrs
-Aggressive chemoRx of malignancies -Increasing #’s of transplants -Expanding usage of immunosuppressive Rxs -HIV epidemic -Increasing encroachment of humans into sylvan habitats As a consequence, incidence of, & mortality due to, IFIs has significantly ↑’ed |
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Invasive fungal infections diagnosis
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Epidemiology
Clinical features Radiographic findings Histopathology -Potassium hydroxide (KOH) -Gomori methenamine silver (GMS) -Periodic acid-Schiff (PAS) Culture -Sabouraud’s or brain heart infusion agar Serology or antigen detection |
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Blastomycosis epidemiology
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Endemic to southeastern/south central US, the Great Lakes region, & near St. Lawrence River
Acquired via inhalation during outdoor activities near decaying vegetation, moist soil, or body of water |
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Blastomycosis clinical features
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Majority of infected pts manifest clinical disease (≥ 90%)
Causes an acute or chronic pneumonia May disseminate to skin, bone, GU tract, or liver Mimics malignancy (esp. lung and skin) |
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Cutaneous blastomycosis
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Beefy red, black spots
Clear borders |
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Blastomycosis diagnosis
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Smears & histopath
-8-15 µm multinucleate broad-based budding yeasts with thick refractile walls (KOH, GMS, PAS) Culture -Sabouraud dextrose agar or brain-heart infusion agar; up to 5 wks to grow (as a mould) Serology -Not reliable; can never be used to “rule in or rule out” disease Antigen detection -Increasingly utilized as diagnostic test; serum & urine |
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Blastomycosis treatment
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Severe disease
-Amphotericin B -≥ 2 wk induction course, then po azole (itraconazole or fluconazole) Mild to moderate disease -Itraconazole (fluconazole) |
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Blastomycosis key teaching points
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Dimorphic fungus
SE & south central US & Great Lakes area <10% asymptomatic : >90% symptomatic Chronic pneumonia; skin Broad-based budding yeast No useful serology (? serum antigen) Amphotericin or itraconazole |
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Histoplasmosis epidemiology
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Endemic to Ohio & Mississippi River valleys, Mexico, & Central America
Acquired via inhalation of conidia during dust storms or building renovation or near large quantities of bird or bat guano in caves |
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Histoplasmosis clinical features
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Majority of infections asymptomatic; 10% of patients have clinical disease
Pneumonia; mucosal ulcers Disseminated infection +/- CNS involvement in the compromised host |
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Histoplasmosis diagnosis
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Smears & histopath→Ovoid 3-5 µm yeasts with narrow-based budding; often within macrophages; seen best with GMS
Culture→Sab; grows in 2-4 wks; blood & BM w/ 75% sensitivity in disseminated dz Serology→CFT; 1:32 diagnostic; false +’s Antigen detection→Mainstay of dx; urine > blood; sensitivity 75+% Skin testing→Useful for epi not clinincal dx |
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Histoplasmosis treatment
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Severe disease
-Amphotericin B -≥ 2 wk induction course, then po azole Mild to moderate disease -Itraconazole or fluconazole |
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Histoplasmosis key teaching points
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Dimorphic fungus
Mississippi & Ohio River valleys 90+% asymptomatic : <10% symptomatic Pneumonia; disseminated infection Small yeast often within macrophages Serum and urine antigen assays Amphotericin or itraconazole |
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Coccidioidomycosis epidemiology
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Endemic to southwestern US (epicenter in south central Arizona), Mexico, & S. America→Travel hx
Inhalation of arthrospores when arid, sandy desert soil is disturbed→Military maneuvers in the desert; archaeological digs; off-road riding, etc |
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Coccidioidomycosis clinical features
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60% of infxns asymptomatic
Acute or chronic pneumonia Disseminated disease→Skin, bones and joints, CNS Erythema nodosum |
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Coccidioidomycosis diagnosis
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Smears & histopath→PAS or GMS stains which demonstrate spherules with endospores
Culture→Grows on routine media as well as Sab; may appear within 1 wk; BC occ’ly + Serology→IDT or CFT are serologic tests of choice; CFT useful in predicting dissemination (1:16) & in following progression of disease/response to Rx Skin testing→Useful as epidemiologic tool |
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Coccidioidomycosis treatment
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“Uncomplicated” pneumonia
-“Watchful waiting” (predictors of progression) or itraconazole Progressive pneumonia or disseminated infection -Amphotericin B or itraconazole CNS infection -Fluconazole |
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Coccidioidomycosis key teaching points
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Dimorphic fungus
Southwestern US 60% asymptomatic : 40% symptomatic Pneumonia; CNS infection Spherules with endospores Complement fixation serology Amphotericin or itraconazole (fluconazole) |
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Candidiasis overview
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Spectrum of infections that encompasses cutaneous, mucosal, and deeply invasive disease→Endogenous in origin
Deeply invasive infections may manifest as fungemia, disseminated disease with multiorgan involvement, or single organ disease Candida species are most frequent cause of IFI in neutropenic hosts & surgical ICU pts Candida species are the 4th most common cause of BSIs in US (7.6%) with an associated crude mortality rate of 40% 25-50% of Candida infections occur in pts in ICUs C. albicans is the most common species causing infection but the non-albicans species are increasing in frequency -? Greater risk for invasion→dissemination -Higher incidence of antifungal drug resistance --C. glabrata→30% resistant to fluconazole --C. krusei→91% resistant to fluconazole |
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Candidiasis diagnosis
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Identification of “typical” clinical features
Biopsies of involved tissues that reveal yeast and/or pseudohyphae Cultures of blood or involved tissues NO useful serologies or antigen detection techniques |
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Candidiasis treatment
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Amphotericin B (or lipid formulations), azoles (fluconazole, itraconazole, voriconazole), or echinocandins (caspofungin, micafungin, anidulafungin)
Choice of agent and duration of Rx dependent upon type disease, severity, & causative species Removal of foreign bodies (ie, IV catheters) and drainage of abscesses may be impt management adjuncts |
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Candidiasis key treatment points
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Yeast
Normal human flora (GI, skin) Colonizer or pathogen Associated with ↓PMNs, ↓CMI, or ICU stay Mucosal disease; fungemia; visceral abscesses Yeast &/or pseudohyphae No useful serologies; culture of blood or tissue Amphotericin, azoles, echinocandins |
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Cryptococcosis epidemiology
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Immunocompromised pts with defects in T cell function (ie, HIV pts, pts receiving high dose steroids, transplant recipients); sporadic disease in normal hosts
Inhalation of spores from soil or bird droppings or around eucalyptus or fir trees (ie, exogenous in origin) |
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Cryptococcosis clinical features
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1˚ manifestation of dz is meningitis; 10% of pts will have cryptococcomas
~10% of pts will have overt pulmonary dz Cutaneous manifestations are varied but may occur in 10-20% of pts |
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Cryptococcosis diagnosis
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Smears & histopath→Organisms may be demonstrable in clinical specimens with KOH, India ink, GMS, & PAS [Mucicarmine]
Culture→Organism grows within 3-5d on both routine & fungal media; extraneural cxs often + with disseminated infxn (Blood, urine) Serology→Not clinically useful Antigen detection→One of mainstays of dx; + in ~50% of pts with pulmonary dz & 90-100% of pts with CNS infxn |
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Cryptococcosis treatment
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Amphotericin B +/- 5 flucytosine x 6 wks
Ampho B +/- 5FC as induction Rx x 2 wks, followed by po fluconazole x 8-10 wks Fluconazole alone |
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Cryptococcosis key teaching points
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Yeast
Ubiquitous in soil (bird droppings) Opportunistic pathogen→↓CMI Meningitis>>pneumonia Narrow-based budding yeast with capsule Serum and CSF antigen assays Amphotericin +/- 5FC or fluconazole |
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Aspergillosis overview
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Aspergillosis is the most common form of invasive filamentous fungal disease (IFFD) in humans, with A. fumigatus the most common causative agent (Property of angioinvasion)
Inhalation of airborne spores is the usual route of infection (exogenous in origin)→Pneumonia is most common type of IA (>50% of pts) Almost all pts with IA have an underlying immunocompromising condition (98%); < 5% of disease occurs in “normal hosts” |
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Invasive pulmonary aspergillosis
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Rapidly progressive disease, often disseminated, occurring in markedly immunocompromised pts, esp those with prolonged & severe neutropenia
Classic radiographic findings include a pleural based infiltrate, the “halo” sign (90%), or the “air-crescent” sign (~60%) Organisms may or may not be demonstrable in sputum or bronchoalveolar lavage fluid specimens |
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Invasive aspergillosis other forms
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Sinonasal disease
CNS disease Cutaneous infection |
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Invasive aspergillosis diagnosis
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Clinical features and radiographs may suggest diagnosis but are not definitive
Whenever possible, dx should be based on compatible tissue histo + positive cx Remember that tissue histology alone is not specific for Aspergillus Serum antigen detection (galactomannan) is an evolving diagnostic test |
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Invasive aspergillosis treatment
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Primary Rx of proven or probable dz
-Voriconazole Salvage Rx for non-responders Lipid formulation of -Amphotericin B -Caspofungin (Micafungin) -Itraconazole -Combination therapies Role of surgery w/pulmonary & sinus dz |
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Aspergillosis key teaching points
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Mould
Ubiquitous in the environment→Spore Opportunistic pathogen→↓PMNs>↓CMI Pneumonia>sinusitis>other Septated hyphae w/ acute angle branching Galactomannan antigen assay Rx: Voriconazole>Ampho>Caspo or Itra |
