Transcript Slide 1

MD Anderson case
Citiwide Oct 7/2009
Viruses
Nabil Khoury MD
UT ID fellow
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

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





Daunorubicin
Vincristine
PEG-L-asparaginase
Prednisone 110 mg/day
Intrathecal MTX
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

Discharged on:


Levaquin 500 mg po qd
Continue:



Bactrim
Valtrex
Itraconazole
Admit on 12/11/2008






Fever 39 C
Chills
Fatigue
Sore throat
Anorexia, nausea and vomiting
No cough, no dyspnea

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









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
Neutropenia Graph
Chest X-ray on 12/11/2008

12/11/2008
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

12/13/2008
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 note: Fever, dry cough, no dyspnea
Exposure to tick bites
Temp max 39C
Differential Diagnosis and Work-up?
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

12/15/09

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

Decision was made to add:


Ambisome and Bactrim
d/c doxycycline




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

1/21
1/21/2009




Not being compliant with Posaconazole
2/18/2009: Admit for severe hemoptysis
Required urgent embolization
2/23: Wedge resection of left upper lobe
Pathology

Lung parenchyma with fungal organism,
morphologically consistent with:
Zygomyces
And associated extensive granulomatous
inflammation and necrosis.
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

Knowing the pathogenesis helps understand
risk factors, manifestations and later on
therapeutic implications
Pathogenesis
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






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






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


Final diagnosis: Biopsy or Autopsy
No blood markers available such GM, Histo or
Crypto antigen
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




Multiple nodules >=10 (>1 cm each)
Sinusitis
Pleural effusion
Reverse halo sign:

Focal area of ground-glass attenuation
surrounded by a ring of consolidation
Reverse halo sign
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

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
CID Jun 16, 2008
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




Iron chelation: deferasirox po x 2-4 wks
Hyperbaric oxygen
Granulocyte transfusions
Cytokine therapy: INF-gamma, G-CSF or
GM-CSF
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

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