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MD Anderson case Citiwide Oct 7/2009

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

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  1. MD Anderson caseCitiwide Oct 7/2009 Nabil Khoury MD UT ID fellow Parasites Fungi Bacterias Viruses

  2. 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

  3. 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

  4. Chemotherapy • Daunorubicin • Vincristine • PEG-L-asparaginase • Prednisone 110 mg/day • Intrathecal MTX

  5. 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

  6. Discharged on: • Levaquin 500 mg po qd • Continue: • Bactrim • Valtrex • Itraconazole

  7. Admit on 12/11/2008 • Fever 39 C • Chills • Fatigue • Sore throat • Anorexia, nausea and vomiting • No cough, no dyspnea

  8. 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

  9. 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

  10. Neutropenia Graph

  11. Chest X-ray on 12/11/2008 • 12/11/2008

  12. 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

  13. 12/13/2008

  14. 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.

  15. ID consult 12/14 • ID note: Fever, dry cough, no dyspnea • Exposure to tick bites • Temp max 39C

  16. Differential Diagnosis and Work-up?

  17. 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

  18. 12/15/09

  19. 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!

  20. 12/19/2009 on SundayAnother ID attending re-evaluating • Decision was made to add: • Ambisome and Bactrim • d/c doxycycline

  21. 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

  22. 1/21 • 1/21/2009

  23. Not being compliant with Posaconazole • 2/18/2009: Admit for severe hemoptysis • Required urgent embolization • 2/23: Wedge resection of left upper lobe

  24. Pathology • Lung parenchyma with fungal organism, morphologically consistent with: Zygomyces And associated extensive granulomatous inflammation and necrosis.

  25. 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.

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

  27. Pathogenesis

  28. 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?

  29. 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..

  30. 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%

  31. Diagnosis • Final diagnosis: Biopsy or Autopsy • No blood markers available such GM, Histo or Crypto antigen

  32. Classic radiological signs for ‘fungal’ Dense well circumscribed lesion with or without halo sign Air-crescent sign Cavity

  33. 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

  34. Reverse halo sign

  35. 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

  36. 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

  37. CID Jun 16, 2008

  38. 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.

  39. Adjunctive therapy Iron chelation: deferasirox po x 2-4 wks Hyperbaric oxygen Granulocyte transfusions Cytokine therapy: INF-gamma, G-CSF or GM-CSF

  40. 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

  41. 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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