MD Anderson caseCitiwide Oct 7/2009

Nabil Khoury MD

UT ID fellow

BacteriasFungi

Viruses

Parasites

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 SundayAnother 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 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

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