Presents with 2day history of weakness dizziness left calf pain and black tarry stools Denies chest pain cough or shortness of breath Medical history Diabetes leading to renal failure and renal transplant ID: 775063
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Slide1
Invasive Aspergillosis
34-year-old womanPresents with 2-day history of weakness, dizziness, left calf pain, and black tarry stools.Denies chest pain, cough, or shortness of breathMedical history:Diabetes leading to renal failure and renal transplant3 weeks before presentation, acute graft rejection developedBegan an immunosuppressive regimen
Guha
, et al. Infect Med 24 (
Suppl
8): 8-11, 2007
Slide2Invasive Aspergillosis
On admissionTachycardic, hypotensive and febrileInitial chest x-ray was normalLab results:AnemiaWBC = 4800/µl, 80% neutrophilsBlood cultures were positive for E. coliAntibiotic therapy initiated
Guha
, et al. Infect Med 24 (
Suppl
8): 8-11, 2007
Slide3Invasive Aspergillosis
Day 6:Vesicular rash developed on buttocks and left calfCultures positive for HSV, antiviral therapy initiatedDay 8:Renal function continued to declineIntermittent hemodialysis startedDay 12:Decreased responsivenessIntubated for respiratory distress
Guha
, et al. Infect Med 24 (
Suppl
8): 8-11, 2007
Slide4Invasive Aspergillosis
Chest x-ray:Diffuse bilateral lung nodulesCulture of BAL:Positive for Aspergillus spp.Immunesuppression decreasedLiposomal Amphotericin B startedCondition deteriorates:Acute MI, comatoseMulitple acute infarcts in frontal lobe and cerebellum by MRIMultiple skin nodules form on arms and trunk
Guha
, et al. Infect Med 24 (
Suppl
8): 8-11, 2007
Slide5Invasive Aspergillosis
Culture of skin nodule biopsy:Aspergillus spp.
Guha
, et al. Infect Med 24 (
Suppl
8): 8-11, 2007
Slide6Aspergillosis
Epidemiology:
Most common fungus worldwide – Ubiquitous
Hospital acquired infection - Major problem
Virulence factors and pathogenesis:
Thermo-tolerant to 50
C
Elastase
,
phospholipase
, protease and
catalase
Conidia bind to fibrinogen and
laminin
Invasive disease is dependent on impaired
neutrophil
function
Unable to generate the oxidative burst to kill
AT RISK:
Severe
neutropenia
, leukemia and lymphoma.
Slide7Aspergillosis - Clinical Aspects
Clinical Manifestations: Route of infection: InhalationIncubation: days to weeksForms of infections: Allergic aspergillosisCavitary colonization - aspergilloma Primary pulmonary aspergillosisInvasive aspergillosis
Slide8Types of
A
spergilloses
Slide9ABPA – Allergic broncopulmonary aspergillosis (ABPA)
AsthmaPulmonary infiltratesPeripheral eosinopheliaElevated serum IgEHypersensitivity to Aspergillus antigenSkin test
Slide10Aspergilloma
Colonization of paranasal sinuses and the lower airways
Obstructive bronchial aspergillosisOccurs in pre-formed cavitary lesionsCystic fibrosisChonic bronchitisTBNo tissue damage, asymptomatic
Slide11Disseminated invasive aspergillosis
Slide12Laboratory Diagnosis
: Monomorphic true mouldDifficult because of the universality of the fungusREPEAT ISOLATIONS ARE ESSENTIAL FOR DEFINITIVE DXSerum: galactomannan Ag + invasive aspergillosisHistopathology: Septate hyphaedichotomous branching at ACUTE anglesMay see full conidial structures (i.e. fruiting bodies) In culture: A. fumigatus – “rapid grower” Septate, hyaline hyphaeconidiophores with phialidespointing upwards, bearing chains of conidia
Aspergillosis – Laboratory Diagnosis
Slide13Direct prep from tissue specimen
Acute, dichotomous branching
Aspergillosis
Slide14Septate hyphae
Aspergilloma
Conidiophore “fruiting body”
Aspergillosis
Slide15Aspergillosis
Slide16Aspergillosis
A. fumigatus
Slide17Aspergillosis - Treatment
Treatment
:
Invasive disease is difficult to treat
Amphotericin
B,
caspofungin
(
echinocandins
),
voriconazole
Decrease
immunosuppression
or reconstitute immune defenses
Surgical debridement, if possible
Prevention in high-risk patients:
Neutropenic
: Filtered air to minimize exposure!
Slide18Invasive Aspergillosis
Our patient:Expired on hospital day 23At autopsy, A. flavus was detected in multiple organs:Heart, lungs, adrenal galnd, thyroid, kidney, and liverExtreme example of disseminated aspergillosis in an immunocompromised host
Guha
, et al. Infect Med 24 (
Suppl
8): 8-11, 2007
Slide19Opportunistic hyalohyphomycoses
Diverse agents
Many are ubiquitous – inhaled conidia
Many are resistant to antifungal agents
In tissue, they appear indistinguishable from
Aspergillus
!
(i.e. branching,
septate
hyphae)
Repeated isolation from multiple sites/multiple times
is best criteria to determine clinical significance.
BOTTOM LINE
: CULTURE IS CRITICAL FOR DX & TREATMENT
Slide20Disseminated infection is increasing in incidence Some examples:Fusarium (R to ampB), immune reconst. + new triazolesScedosporium (R to ampB) – surgical resectionAcremonium (S unestablished)Paecilomyces – voriconazole…and many, many more.
Fus
Sce
Acr Pae
Opportunistic
hyalohyphomycoses
Slide21Phaeohyphomycoses
Many are neurotropic: present as brain abscesses, sinusitis CNSBOTTOM LINE:Response to therapy is unpredictable between generaCulture is critical for diagnosis and therapy
Slide22In tissue:Pigmented hyphae w/ or w/o yeast are presentDisseminated infection is increasing:Alternaria, Curvularia, Bipolaris, Cladosporium…and others
Alt
Cur
Bip
Cla
Phaeohyphomycoses
Slide23Pneumocystosis
Etiology:
Pneumocystis
jirovecii
Most common opportunistic infection among individuals with AIDS
Incidence has decreased significantly with HAART
Reservoir in nature unknown
Pneumonia is clearly the most common presentation
Interstitial
pneumonitis
, mononuclear infiltrate
Onset insidious
Diagnosis based on microscopic examination of BAL