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ID Case Conference November 15, 2004


76-year-old white male with AML diagnosed in June 2004 which evolved from a ... (MIC rage 0.25-16) . Despite its limited in vitro activity, posaconazole appears ... – PowerPoint PPT presentation

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Title: ID Case Conference November 15, 2004

ID Case Conference November 15, 2004
  • Elizabeth Palavecino, M.D.
  • Director Clinical Microbiology

Microbiologic Diagnosis Case 1.
  • 76-year-old white male with AML diagnosed in June
    2004 which evolved from a preceding MDS. He was
    admitted for induction chemotherapy, but failed
    to show remission. A second induction was
  • During the patients course, he did experience
    neutropenic fevers and had persistent bleeding
    from his right nasal cavity. Nasal examination
    revealed an area of discoloration (1x1 cm) of the
    right septum.
  • The patient was taken to the OR on July 10 for
    evaluation and the patient was found to have an
    ulcerated granular lesion of the right nasal
    septum. Debridment of nasal mucosa and underlying
    cartilage was performed. Nasal tissue was sent
    for path diagnosis and for culture.

Biopsy nasal septum hematoxilin-eosin (HE)
stain showing septate hyphae
Biopsy of Nasal Septum Gomoris Methenamine
silver (GMS 40x) Report Angioinvasive fungal
infection consistent with Aspergillus or Fusarium
Microbiologic diagnosis Case 2
  • 17-year-old white female diagnosed with B-lineage
    acute lymphoblastic leukemia on Feb 04. Admitted
    for chemotherapy
  • During her hospital course she developed fever
    and acute descompensation. She was treated with
    broad spectrum antibiotics. Four days into the
    antibiotic course, she developed a diffuse skin
    rash. A biopsy was obtained for pathology
    diagnosis and culture.

Skin Biopsy Report Findings consistent with
Aspergillosis. Tissue culture will help with
definitive diagnosis
Microbiologic Diagnosis Case 3
  • 34-year-old male with chronic sinusitis
    refractory to antibiotic therapy. On 2002 he had
    nasal surgery and the biopsy from tissue revealed
    fungal infection consistent with aspergillosis.
    He was treated with nasal Ampho B irrigation, but
    congestion and pain continued. One month after
    surgery, 200 mg Itraconazole BID was added.
  • He continued having exacerbations, he received
    multiple antibiotic and prednisone courses. He
    became progressively worse over the past eight
  • On Sep 04 the patient underwent extensive

Biopsy of nasal septum HE
Biopsy Nasal Septum GMS Report Fungal hyphae
consistent with Aspergillus. Numerous eosinophils
(seen HE)
GMS from the three cases
Question 1 Do you think these infections are
caused by the same organism?
  • a. Yes
  • b. No
  • c. I dont know
  • d. I need more information

Case 1. Culture results. Colony Morphology
(left) Microscopy-lactophenol staining (right)
Case 2 Culture Results. Colony morphology
(left) and microscopy (right)
Case 3. Colony morphology and microscopy
Microbiologic diagnosis
  • Case 1. Alternaria spp
  • Case 2. Fusarium spp.
  • Case 3. Bipolaris spp.

Characteristics of the organisms isolated
  • Fusarium Filamentous fungus widely distributed
    on plants and in the soil. More than 20 species.
    The most common of these is Fusarium solani.
    Fusarium spp. are causative agents of superficial
    and systemic infections in human. Disseminated
    opportunistic infections develop in
    immunosuppressed hosts, particularly neutropenic
    and transplant patients.
  • Alternaria and Bipolaris Both are members of the
    dematiaceous filamentous fungi. They are
    cosmopolitan in nature and they isolated from
    plant debris and soil.
  • Bipolaris spp. cause allergic and chronic
    invasive sinusitis, keratitis, osteomyelitis,
    endocarditis and lung disease. Can infect both
    immunocompetent and immunocompromised host.
  • Alternaria spp. Colonize the paranasal sinuses
    in immunocompetent patients, leading to chronic
    hypertrophic sinusitis. In immunocompromised
    host, colonization may lead to invasive disease.

  • Definition Group of mycotic infections caused by
    dematiaceous fungi.
  • Dematiaceous fungi Fungi that have dark
    pigmented cell wall due to presence of melanin.
    About 60 genera and gt100 species. They cause
    three different pathologic conditions
    phaeohyphomycosis, chromoblastomycosis, and
  • Member of this group include Cladophialophora
    spp, Curvularia spp, Bipolaris spp, Exophiala
    spp, Scedosporium spp, Phialophora spp, Wangiella

Histopathology and Microbiologic Diagnosis
  • Aspergillosis Typically shows septate hyphae
    with dichotomous (45o angle) branching, straight
    walled hyphae.
  • Dematiaceous fungi Usually present irregularly
    swollen or distorted hyphae with yeast-like
    structures also present.
  • Microbiologic diagnosis Septate hyphae from
  • Paranasal sinus could be Alternaria, Curvularia,
    Scedosporium spp, Bipolaris and other dematiceous
    fungi. Also Aspergillus, Fusarium, Acremoniun,
  • From skin Aspergillus, Fusarium,
    Cladophialophora, Exophiala, Wangiella,
    Fonsecaea, Scedosporium spp., Dermatophytes

Susceptibility patterns
  • Fusarium spp Resistant to most antifungal
    agents. The only antifungal drugs that yield
    relatively low MICs for Fusarium are Amph B (MIC
    50 2ug/ml,MIC 90 8ug/ml) , voriconazole (MIC
    rage 0.25-16) . Despite its limited in vitro
    activity, posaconazole appears effective in
    murine fusariosis.
  • Alternaria spp Limited data, but caspofungin and
    voriconazole have lower MIC than itraconazole for
    Alternaria strains
  • Bipolaris spp Limited data. Itraconazole MICs
    are variable and reported voriconazole MICs are

Disseminated Phaeohyphomycosis Review of an
Emerging Mycosis. Revankar SG., CID 2002
34467-76 (review of 72 cases published in the
  • The most common pathogens were Scedosporium
    prolificans (30), Bipolaris spp (8), Wangiella
    spp (5), Curvularia spp (5), Exophiala spp. (4).
    Note 80 of S prolificans were isolated in Spain
    and Australia.
  • The primary risk factor is decreased host
    immunity, but infections have been reported in
    immunocompetent and immunosuppressed patients.
  • Eosinophilia was seen in 11 of the cases,
    particularly in infections caused by Bipolaris
    spp and Curvularia spp. Phaeohyphomycosis should
    be added to the list of infections associated
    with eosinophilia.
  • Endocarditis is mostly reported on bioprosthetic
    valves, mainly those of porcin origin.
  • More than half of case had positive culture
    (Scedosporium prolificans was responsible for 70
    of the positive blood cultures). S prolificans is
    resistant to most antifungals. S apiospermum is
    susceptible to miconazole, voriconazole and

Mould Infections In Hematopoietic Stem Cell
Transplant Patients. Marr KA, CID 2002 34909.
Data from Fred Hutchinson Cancer Research Center
in Seattle from 1985-1999.
  • Non-Aspergillus moulds isolated
  • Zygomycetes (40)
  • Fusarium (39)
  • Dematiaceous (18) Scedosporium spp (10),
    Alternaria spp (5), Exophiala spp (3)
  • Paecilomyces (14)
  • The results of this study emphasize the
    importance of severe neutropnia in the disease
    caused by Scedosporium species.
  • Infections cused by Zygomycetes (Rhizopus spp,
    Mucor spp, and Absidia spp) have a stroger
    association with GVHD and its therapy
  • Patients who developed infection with Fusarium
    and Scedosporium had frequent dissemination to
    other tissues.
  • In contrast, most Fusarium infections in organ
    transplant recipient are localized.

Primary Central Nervous System Phaeohyphomycosis
A review of 101 Cases. Revankar SG. CID 2004
  • Most frequent pathogens
  • Cladophialophora bantiana
  • Ramichloridium mackenziei. (patients from Middle
  • More than one-half of the cases ocurred in
    patients with no known underlying
    immunodeficiency. C bantiana must be processed
    under Biosafety Level 2 in the laboratory
  • Mortality rates were high regardless of immune
  • Ampho B in combination with flucytocine, and
    itraconazole may improve survival.
  • Voriconazole and the newer azole derivatives
    posaconazole and ravuconazole have activity
    against dematiaceous fungi.

Positive Cultures for Saprophytic Moulds in
Cancer Patients. Lionakis MS. Clin Microbiol
Infect 2004 10 922. Anderson Cancer Center,
Houston, TX. 7-year period.
  • 30 cancer patients with positive cultures for
    saprophytic moulds, representing 1 of all
    positive fungal cultures.
  • Aspergillus spp. are the commonest moulds causing
    invasive mould infections, but they are rarely
    isolated from blood specimens
  • Fusarium spp. can be isolated from 60-70 of
    blood specimens from patients with disseminated
  • Most frequent organisms from clinically
    significant fungemia (patients with Aspergillus
    and Fusarium positive blood cultures were
  • Scedosporium spp S apiospermun (4), S
    prolificans (1).
  • Non- Scedosporium moulds Aureobasidium spp (14),
    Paecilomyces (4), Alternaria (3).
  • True fungemia was seen only in leukemia patients
    and allogeneic bone marrow transplant recipients.
    All mould positive blood culture from patients
    with solid tumor were false positive.

New Treatment Strategies.
  • Davis SR. The in vitro susceptibility of
    Scedosporium prolificans to ajoene, allitridium
    and a raw extract of garlic. J Antimicrob
    Chemother 2003 51593-597.
  • The results demonstrate that both garlic
    derivatives and raw garlic extract appear to have
    in vitro activity against S prolificans.

Immunocompetent patient with brain abscess. Brain
Biopsy (HE) showing septate hyphae The most
probable causative organism is
Culture results
  • Cladophialophora bantiana!

GMS from nasal tissue of a renal transplant
patient. What is your diagnosis?
Culture result
  • Aspergillus terreus!!!