34-year-old woman Presents with 2-day history of weakness, dizziness, left calf pain, and black...
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Invasive Aspergillosis 34-year-old woman • Presents with 2-day 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 • 3 weeks before presentation, acute graft rejection developed • Began an immunosuppressive regimen Guha, et al. Infect Med 24 (Suppl 8): 8-11, 2007
34-year-old woman Presents with 2-day history of weakness, dizziness, left calf pain, and black tarry stools. Denies chest pain, cough, or shortness
34-year-old woman Presents with 2-day 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 3 weeks before
presentation, acute graft rejection developed Began an
immunosuppressive regimen Guha, et al. Infect Med 24 (Suppl 8):
8-11, 2007
Slide 2
On admission Tachycardic, hypotensive and febrile Initial chest
x-ray was normal Lab results: Anemia WBC = 4800/l, 80% neutrophils
Blood cultures were positive for E. coli Antibiotic therapy
initiated Guha, et al. Infect Med 24 (Suppl 8): 8-11, 2007
Slide 3
Day 6: Vesicular rash developed on buttocks and left calf
Cultures positive for HSV, antiviral therapy initiated Day 8: Renal
function continued to decline Intermittent hemodialysis started Day
12: Decreased responsiveness Intubated for respiratory distress
Guha, et al. Infect Med 24 (Suppl 8): 8-11, 2007
Slide 4
Chest x-ray: Diffuse bilateral lung nodules Culture of BAL:
Positive for Aspergillus spp. Immunesuppression decreased Liposomal
Amphotericin B started Condition deteriorates: Acute MI, comatose
Mulitple acute infarcts in frontal lobe and cerebellum by MRI
Multiple skin nodules form on arms and trunk Guha, et al. Infect
Med 24 (Suppl 8): 8-11, 2007
Slide 5
Culture of skin nodule biopsy: Aspergillus spp. Guha, et al.
Infect Med 24 (Suppl 8): 8-11, 2007
Slide 6
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.
Slide 7
Clinical Manifestations: Route of infection: Inhalation
Incubation: days to weeks Forms of infections: Allergic
aspergillosis Cavitary colonization - aspergilloma Primary
pulmonary aspergillosis Invasive aspergillosis
Slide 8
Types of Aspergilloses
Slide 9
Asthma Pulmonary infiltrates Peripheral eosinophelia Elevated
serum IgE Hypersensitivity to Aspergillus antigen Skin test
Slide 10
-Colonization of paranasal sinuses and the lower airways
-Obstructive bronchial aspergillosis -Occurs in pre-formed cavitary
lesions -Cystic fibrosis -Chonic bronchitis -TB -No tissue damage,
asymptomatic
Slide 11
Slide 12
Laboratory Diagnosis: Monomorphic true mould Difficult because
of the universality of the fungus REPEAT ISOLATIONS ARE ESSENTIAL
FOR DEFINITIVE DX Serum: galactomannan Ag + invasive aspergillosis
Histopathology: Septate hyphae dichotomous branching at ACUTE
angles May see full conidial structures (i.e. fruiting bodies) In
culture: A. fumigatus rapid grower Septate, hyaline hyphae
conidiophores with phialides pointing upwards, bearing chains of
conidia Aspergillosis Laboratory Diagnosis
Slide 13
Direct prep from tissue specimen Acute, dichotomous branching
Aspergillosis
Slide 14
Septate hyphae Aspergilloma Conidiophore fruiting body
Aspergillosis
Slide 15
Aspergillosis
Slide 16
Aspergillosis A. fumigatus
Slide 17
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!
Slide 18
Our patient: Expired on hospital day 23 At autopsy, A. flavus
was detected in multiple organs: Heart, lungs, adrenal galnd,
thyroid, kidney, and liver Extreme example of disseminated
aspergillosis in an immunocompromised host Guha, et al. Infect Med
24 (Suppl 8): 8-11, 2007
Slide 19
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
Slide 20
Disseminated infection is increasing in incidence Some
examples: Fusarium (R to ampB), immune reconst. + new triazoles
Scedosporium (R to ampB) surgical resection Acremonium (S
unestablished) Paecilomyces voriconazole and many, many more. Fus
Sce Acr Pae Opportunistic hyalohyphomycoses
Slide 21
Many are neurotropic: present as brain abscesses, sinusitis CNS
BOTTOM LINE: Response to therapy is unpredictable between genera
Culture is critical for diagnosis and therapy
Slide 22
In tissue: Pigmented hyphae w/ or w/o yeast are present
Disseminated infection is increasing: Alternaria, Curvularia,
Bipolaris, Cladosporiumand others Alt Cur Bip Cla Phaeohyphomycoses
Phaeohyphomycoses
Slide 23
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