ID Case Conference November 15, 2004

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ID Case Conference November 15, 2004

• Elizabeth Palavecino, M.D.
• Director Clinical Microbiology

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Microbiologic DiagnosisCase 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
  started.
• 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.

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Biopsy nasal septum hematoxilin-eosin (HE)
stain showing septate hyphae
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Biopsy of Nasal Septum Gomoris Methenamine
silver (GMS 40x)Report Angioinvasive fungal
infection consistent with Aspergillus or Fusarium
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Microbiologic diagnosisCase 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.

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Skin Biopsy Report Findings consistent with
Aspergillosis. Tissue culture will help with
definitive diagnosis
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Microbiologic DiagnosisCase 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
  months
• On Sep 04 the patient underwent extensive
  surgery.

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Biopsy of nasal septum HE
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Biopsy Nasal Septum GMS Report Fungal hyphae
consistent with Aspergillus. Numerous eosinophils
(seen HE)
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GMS from the three cases
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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

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

• Case 1. Alternaria spp
• Case 2. Fusarium spp.
• Case 3. Bipolaris spp.

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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.

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Phaeohyphomycosis

• 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
  mycetoma.
• Member of this group include Cladophialophora
  spp, Curvularia spp, Bipolaris spp, Exophiala
  spp, Scedosporium spp, Phialophora spp, Wangiella
  spp.

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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,
  Paecilomyces.
• From skin Aspergillus, Fusarium,
  Cladophialophora, Exophiala, Wangiella,
  Fonsecaea, Scedosporium spp., Dermatophytes

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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
  low.

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Disseminated Phaeohyphomycosis Review of an
Emerging Mycosis. Revankar SG., CID 2002
34467-76(review of 72 cases published in the
literature)

• 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
  posaconazole.

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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
  (corticosteroids).
• 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.

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Primary Central Nervous System Phaeohyphomycosis
A review of 101 Cases. Revankar SG. CID 2004
38206-16.

• Most frequent pathogens
• Cladophialophora bantiana
• Ramichloridium mackenziei. (patients from Middle
  East)
• 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
  setting.
• Mortality rates were high regardless of immune
  status
• 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.

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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
  fusariosis
• Most frequent organisms from clinically
  significant fungemia (patients with Aspergillus
  and Fusarium positive blood cultures were
  excluded)
• 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.

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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.

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Immunocompetent patient with brain abscess.Brain
Biopsy (HE) showing septate hyphaeThe most
probable causative organism is
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Culture results

• Cladophialophora bantiana!

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

• Aspergillus terreus!!!