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Febrile Neutropenia and Fungal Infections

Febrile Neutropenia and Fungal Infections. Lin Chien-ting 林建廷 Dec 4, 2009. 40. 35. 30. 25. 20. 15. 10. 5. 0. Febrile Neutropenia (FN). 39. 60. 53. 50. 37. 40. 19. 發燒 (%). 30. 感染 (%). 22. 11. 20. 10. 11. 10. 3. 0. 0. 2. 0. 1. 3. > 4. <100. 100- 500.

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Febrile Neutropenia and Fungal Infections

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  1. Febrile Neutropenia and Fungal Infections Lin Chien-ting 林建廷 Dec 4, 2009

  2. 40 35 30 25 20 15 10 5 0 Febrile Neutropenia (FN) 39 60 53 50 37 40 19 發燒 (%) 30 感染 (%) 22 11 20 10 11 10 3 0 0 2 0 1 3 >4 <100 100- 500 500- 1000 1000- 1500 >1500 Severe Neutropenia天數 (日) ANC數目(/μL)

  3. 找出感染源--esp. Hx of sinusitis and hemorrhoid 牙齦, 口腔黏膜, 鼻竇—HSV/ Candida/mold CVP, Port-A, PICC: G(+)/ G(-)/ fungus Abd/perianal: enterococci/ G(-)/ anaerobes 肺部: bacteria, PJP, CMV, fungus Diarrhea: C. difficile 即使很完整的評估, 只有大約 50 ~70% 可以確定感染源

  4. Febrile Neutropenia-- EtiologyNTUH, 1996-2001 (%) 57 32 7 3 Chen CY et al. J Formos Med Assoc 2004;103:526-32.

  5. Febrile Neutropenia– Etiology1996-2001, NTUH MRSA, 67% of Stapylococcus C, tropicalis.C. albicans % Chen CY et al. J Formos Med Assoc 2004;103:526-32.

  6. Initial Management of FN IDSA 2002 FN Low risk High risk Vancomycin Not needed Vancomycin needed IV Oral Vancomycin + Ciprofloxacin + Amoxicillin-clavulanate (adults only) Two Drugs Monotherapy Vancomycin+ Cefepime, ceftazidime or Carbapenem  aminoglycoside Aminoglycoside+ Antipseudomonal penicillin, Cef Cefepime, Ceftazidime, or carbapenem Cefepime, Ceftazidime, or Carbapenem Reassess after 3-5 days Hughes WT et al. Clin Infect Dis 2002;34:730-51.

  7. Factors that favor a Low Riskfor severe infections during Neutropenia • ANC > 100 cells/mm3 • AMC >100 cells/mm3 • Normal CXR • Nearly normal RFT and LFT • Duration of neutropenia < 10 days • No CVC infection • Malignancy in remission • BT <39 °C • No neurological or mental status changes • No abd pain • No appearance of illness • No co-morbidity Laboratory Clinical

  8. Resistant Gram (-) Blood Pathogens 1996-2001, NTUH (%) Chen CY et al. J Formos Med Assoc 2004;103:526-32.

  9. Algorithm for Initial Management of FN Taiwan FN Guidelines 2005 FN Low risk High risk Glycopeptided Not needed Glycopeptide needed IV Oral Two Drugs (B) A glycopeptided Monotherapy (A) A fluoroquinolone a + Amoxicillin-clavulanate or Ampicillin-sulbactam (adults) A cephalosporinb  An aminoglycoside An aminoglycosidec+ Ceftazidime, Piperacillin-tazobactam, Cefepime, Cefpirome or A carbapenemc Cefepime, Cefpirome, Piperacillin-tazobactam, A carbapeneme + A or B Reassess after 3-5 days a Includes ciprofloxacin, levofloxacin, or moxifloxacin b Includes a first-, second-, or third-generation cephalosprin c Includes amikacin or isepamicin d Includes vancomycin or teicoplanin e Includes imipenem or meropenem

  10. 抗生素 及 G-CSF 預防性使用對發燒的影響 Levofloxacin Pegfilgrastim P = .001 90 90 Placebo Placebo 80 80 70 70 P <.001 60 60 50 50 發燒(%) 發燒(%) 40 40 30 30 P = .01 20 20 10 10 0 0 Cullen, et al. 2005 Bucaneve, et al. 2005 Vogel, et al. 2005 *Cycle 1. Cullen M, et al. N Engl J Med. 2005;353:988-998; Bucaneve G, et al. N Engl J Med. 2005;353:977-987; Vogel CL, et al. J Clin Oncol. 2005;23:1178-1184.

  11. 何時要用預防性抗生素? 哪一種藥物好? • 何時要用預防性抗生素? • 幹細胞移植時 (Conditioning chemotherapy) • 預備收集幹細胞時 • 哪一種藥物好? • Cover GPC + GNB • Augmentin 1#bid + Ciproxin 2#bid?

  12. G-CSF 的預防性使用 • Granocyte vs Filgrastim • 在化療結束後 1-3 天開始給予 • 5 µg/kg/day 直到 ANC 恢復 (Max: 10 µg/kg/day ) • WBC>4000, 可先減半 • 仍然WBC>4000, 可DC • AML induction?AML consolidation? • MDS?

  13. Underlying Dz in Invasive Aspergillosis ~60% of all Invasive Aspergillosis !! Clinical Infectious Diseases 2006; 43:S3–14

  14. 400 300 200 number of cases 42% 33% 100 61% 53% 50% 29% 0 Candida Fusarium Aspergillus Trichosporon Zygomycetes Cryptococcus cases casualties Lethality of Invasive Fungal Infections Pagano et al. Haematologica 2006; 91:1068-1075

  15. (1)Host factors • 現在: • Neutropenia > 10 days • Fever > 96 hrs refractory to Abx • GVHD, esp >Gr2 aGVHD or extensive cGVHD • 過去: • Prolonged (> 3 weeks) steroids use in previous 60 days • > 38C or < 36C, AND any of: • Prolonged neutropenia (>10 days) in previous 60 days • Significant immunosuppressive agents in previous 30 days • Proven/ probable IFI during previous episode of neutropenia CID 2002 34: 7-14

  16. (2)Clinical criteria/ Image criteria CID 2002 34: 7-14

  17. Neutropenic fever… 11 days later…

  18. (3)Microbiological criteria CID 2002 34: 7-14

  19. Galactomannan Test • Positive: • Aspergillus • Penicillium • Paecilomyces • Cryptococcus neoformans • Penicillin-like Abx • Cut-point: • 0.5 is well accepted wordwide Medical mycology, 2006, 44, S179-S183

  20. Ravuconazole Caspofungin Anidulafungin Sordarins Micafungin Voriconazole Posaconazole Medical Mycology: No of drugs L-AmB ABCD ABLC Terbinafine Amphotericin B (1958) Itraconazole Griseofulvin Fluconazole Ketoconazole Miconazole Nystatin 5-FC

  21. ? Micafungin 50mg qd IAI IC Caspofungin 70/50 Micafungin 100 Ambisome 3-5 Fluconazole 800/400 Voriconazole

  22. FDA Approved Indications, updated 2009

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