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MD Anderson case Citiwide Oct 7/2009. Nabil Khoury MD UT ID fellow. Parasites. Fungi. Bacterias. Viruses. History First admit to MDA: 10/06/08-10/13/2008.

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md anderson case citiwide oct 7 2009

MD Anderson caseCitiwide Oct 7/2009

Nabil Khoury MD

UT ID fellow

Parasites

Fungi

Bacterias

Viruses

history first admit to mda 10 06 08 10 13 2008
History First admit to MDA: 10/06/08-10/13/2008

A 21 year-old Caucasian male, college student, from Oklahoma without any prior medical history was admitted because of Fever, anemia, thrombocytopenia.

Found to have pre-B ALL.

ANC 800 at that time

Received antibiotics and chemotherapy

Microbiological w/u was negative

antibiotics
Antibiotics
  • During his hospital stay:
    • Cefepime and Linezolid
    • Oral valtrex and Itraconazole as prophylaxis
  • On discharge:
    • Cefepime 2 g IV q 8 x 5 days, then cefpodoxime 200 mg po bid
    • Bactrim DS one tab bid 3 times/week
    • Valtrex 500 mg po qd
    • Itraconazole 20 cc bid
chemotherapy
Chemotherapy
  • Daunorubicin
  • Vincristine
  • PEG-L-asparaginase
  • Prednisone 110 mg/day
  • Intrathecal MTX
second admit to mda 11 21 11 24 08
Second admit to MDA: 11/21-11/24/08
  • Admit for Fever, diarrhea
  • His ANC 200 at that time
  • He was given Cefepime and Vancomycin
  • He became afebrile
  • Work-up: C difficile, Blood and urine C: neg
slide6
Discharged on:
    • Levaquin 500 mg po qd
    • Continue:
      • Bactrim
      • Valtrex
      • Itraconazole
admit on 12 11 2008
Admit on 12/11/2008
  • Fever 39 C
  • Chills
  • Fatigue
  • Sore throat
  • Anorexia, nausea and vomiting
  • No cough, no dyspnea
slide8
Physical Exam:
    • Temp 39 C, BP 107/59, HR 120
    • Cachectic looking
    • Eyes: pale, anicteric sclerae
    • ENMT: no exudate, no ulceration
    • Neck: no goiter, no adenopathies
    • C-V: S1S2 regular, tachy
    • Lungs: decrease breath sound bilaterally, no wheezing or rhonchi
    • Abdomen: Soft, non tender
    • Skin: pale, warm and dry, petechiae appreciated, mac les!!
    • Neuro: AOx3, no evident deficits
    • Picc line RUE: no erythema, no tenderness
work up
Work-up
  • WBC 0.2 – Neutropenic since 11/25
  • Hb 7.5
  • Plt 16,000
  • Alb 2.8
  • Glucose 125
  • Uric acid 1.9
  • Bil 1.4
  • AP 228
  • LDH 302
admit on 12 11 20081
Admit on 12/11/2008
  • He was admitted and started on:
    • Meropenem
    • Vancomycin
    • Micafungin
    • Voriconazole
  • 12/13/2008: Not doing well, febrile.
  • Blood cultures: no growth.
  • GM: negative
  • CMV: negative
  • CT Scan Chest was ordered
ct scan report
CT Scan report
  • Mixed interstitial alveolar infiltrate in the upper lobe of the left lung with some minimal superimposed consolidative changes
  • Minimal adjacent infiltrate in the left lower lobe superiorly.
  • Small left pleural effusion
  • Findings are compatible with a pneumonic process and can be clinically correlated.
id consult 12 14
ID consult 12/14
  • ID note: Fever, dry cough, no dyspnea
  • Exposure to tick bites
  • Temp max 39C
id recommendations
ID recommendations
  • ID recommended to add doxycycline and Amikacin
  • Work-up with Rickettsia, Ehlrichia, anaplasmosis, Crypto and histo atigen
  • Nasal wash for viral cultures
  • Bronchoscopy and BAL to send for:
    • Cultures
    • PCP
    • AFB
  • Skin biopsy for some macular skin lesion
slide21
Meanwhile all the prior work-up including:
    • BAL: negative for AFB, fungi, bacteria, PCP
    • Crypto, Histo negative
    • GM: still negative
  • On sunday 12/19: Still not doing well,

febrile on a daily basis!

    • What do you want to do now?
    • It is almost X-mas!
12 19 2009 on sunday another id attending re evaluating
12/19/2009 on SundayAnother ID attending re-evaluating
  • Decision was made to add:
    • Ambisome and Bactrim
    • d/c doxycycline
slide23
12/20: Getting better, Fever trending down
  • 12/21: Afebrile
  • 12/22: Add posaconazole

and d/c Vori, Caspofungin

  • 12/23: Discharged home on Ambisome, posaconazole, Bactrim,

Linezolid and Cipro

slide24
1/21
  • 1/21/2009
slide25
Not being compliant with Posaconazole
  • 2/18/2009: Admit for severe hemoptysis
  • Required urgent embolization
  • 2/23: Wedge resection of left upper lobe
pathology
Pathology
  • Lung parenchyma with fungal organism, morphologically consistent with:

Zygomyces

And associated extensive granulomatous inflammation and necrosis.

mucormycosis
Mucormycosis
  • Rare and rapidly progressive opportunistic fungal infection
  • Rhizopus>Rhizomucor>Cunninghamella species
  • Many other species to name
  • Ubiquitous fungi: common inhabitants of decaying matter
  • Characterized by: fast-growing fibrous mycelium and thin-walled aseptate or hyposeptate hyphae. Right angle branching is seen.
pathogenesis
Pathogenesis

Knowing the pathogenesis helps understand risk factors, manifestations and later on therapeutic implications

risk factors
Risk Factors

Prolonged neutropenia

Hyperglycemia and acidosis (DKA)

Steroids

Immunosuppressive therapy

Burns, trauma (skin form)

Excess iron

Deferoxamine (not iron chelators in general)

Voriconazole use?

clinical forms
Clinical forms

Rhino-cerebral or cranio-facial (1/3-1/2 of the cases)

Pulmonary

Cutaneous

Gastro-intestinal: rare

Disseminated>90% mortality

Others: endocarditis, kidneys, etc..

pulmonary form
Pulmonary form

High resolution CT Scan may demonstrate evidence of infection before the Chest X-ray

Sputum culture is unreliable

This Mold is difficult to culture

Hematogenous dissemination frequent but blood cultures are negatives

Death may occur before respiratory failure!

Mortality 50-70%

diagnosis
Diagnosis
  • Final diagnosis: Biopsy or Autopsy
  • No blood markers available such GM, Histo or Crypto antigen
classic radiological signs for fungal
Classic radiological signs for ‘fungal’

Dense well circumscribed lesion with or without halo sign

Air-crescent sign

Cavity

radiological findings that favors mucor v s aspergillosis
Radiological findingsthat favors Mucor v/s Aspergillosis
  • Multiple nodules >=10 (>1 cm each)
  • Sinusitis
  • Pleural effusion
  • Reverse halo sign:
    • Focal area of ground-glass attenuation surrounded by a ring of consolidation
treatment
Treatment

Early therapy is crucial: need for high index of suspicion

Reversal of the underlying predisposing factors if possible

Surgical debridement: urgent basis

Appropriate anti-fungal therapy: before definite diagnosis

Other adjunctive therapy

anti fungal therapy
Anti-fungal therapy
  • Amphotericin B:++
    • Liposomal/lipid form: seems better?
      • More tolerated, high doses, long time
  • Echinocandin: has no efficacy by themselves
  • Combination: Ampho B and echinocandin
    • Current trend in MDA
azoles
Azoles
  • Voriconazole: no activity, Mucorales is a major hole in the spectrum
  • Itraconazole: Absidia species only(4%)
  • Posaconazole: has good activity
    • Second line
    • Only po form available
    • Takes 1 week to get to steady state
    • Success as salvage therapy
    • Combination with polyene: no benefit in animal models.
adjunctive therapy
Adjunctive therapy

Iron chelation: deferasirox po x 2-4 wks

Hyperbaric oxygen

Granulocyte transfusions

Cytokine therapy: INF-gamma, G-CSF or GM-CSF

duration of therapy
Duration of therapy?
  • Long enough!
    • Resolution of clinical signs and symptoms
    • Resolution or stabilization of residual radiographic signs of disease
    • Resolution of underlying immunosuppression
    • Posaconazole may be used as chronic suppressive therapy such in SOT, Chemo
hopefully i did not get you bored
Hopefully I did not get you bored
  • References:
    • Recent Advances in the Management of Mucormycosis. CID 12 May 2009
    • Novel prospectives on Mucormycosis. Clinical microbiology review July 2005
    • Zygomycosis: the re-emerging fungal infection. Eur J Clin Microbiol Infect dis 2006
    • Mucormycosis in hematologic patients hematologica 2004
    • Revised Definition of Invasive Fungal Disease CID 20 Feb 2008
    • Treatment of Zygomycosis: current and new options. Journal of antimicrobial chemo 2008
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