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年年年來 amphotericin B(ampho-B) flucytosine 來療切療不 1998 年不識 1 99% 療 88% ampho-b Fluconazole 2,3 說類 I. Amphotericin B Ampho-B polyene antibiotics ergosterol (sterol) 裂療念 (candidiasis) (Aspergillosis) (Blastomycosis) (Cryptoccosis) (Histoplasmosis) (Mucormycosis) (Sporotrichosis) 療不度來療數念都 ampho-b 來療不來 C krusei C glabrata ampho-b ampho-b 量數料 Ward ampho-b 度度 Ampho-B 度律不不良 ampho-b 量 Faix 0.5 1mg/kg 量 ampho-b 量 0.1mg/kg 1mg/kg 量 (0.1mg/kg) 不立不療度 Baley 量 0.5~1mg/kg/day 5 療量 0.5 1.5mg/kg 6-8 不來說念 1mg/kg 量量療不度 14

Donowitz 30 ampho-b 療療 7 14 (0.5mg/kg 量 ) 療量 (Minimal Inhibitory Concentrations MIC) 量 MIC 量列 Amphotericin B 度量 FUNGUS MIC (ug/ml) TOTAL DOSE (mg/kg) Candida species 0.09-3.12 25-30 Cryptococcus 0.2-1.0 15-30 neoformans Coccidiodes immitis 0.78 70 Aspergillus species 1.9-4.0 15-45 Phycomycetes 3.0-6.0 Unknown 類 ampho-b : amphotericin B lipid complex (ABLC or Abelcet) amphotericin B colloidial dispersion (ABCD) liposomal amphotericin B (AmBisome) 9 療 AmBisome 療 ( ) 10, 11 量 1mg/kg/day 5mg/kg/dayg 臨不率 72.7% 92 粒 ampho-b (Liposomal amphotericin B) ampho-b 1 5mg/kg 量療都不 12 5-Fluorocytosine (5-FC) (fluoropyrimidine) 5-fluorouracil 療念 ( 尿 ) ( ) 量 50 150mg/kg 六 ampho-b ampho-b 療 5-FC 來療念療 Imidazole Miconazol imidazole 來 ergosterol 療念 (Coccidioides) 量例來療療 Clotrimazole imidazole 療 Ketoconazole imidazole 念念 (dermatophyte) ketoconazole 療 15

II. Nystatin Nystatin 漏療念療念 III. Griseofulvin 了率狀裂裂來力 Griseofulvin 力量 10mg/kg 療例療料 Ross (10mg/kg/day) 不良見 Azoles 類 Fluconazole azole 類 14- -sterol demethylase( cytochrome P-450 sterol 力療念 Wiest ampho-b 5-fluorocytosine 療 Gurses Kalayci 療年 fluconazole 療不率 68-73% 2, 13 Kaufman 度 (ELBW) fluconazole 度 (colonization) 3 Itraconazole, azole 類不零例不不 Voriconazole fluconazole fluconazole 更 ampho-b 兩 cyclodextrin 不良不糖 (lactose) 糖糖 (galactose) 不不零 voriconazole 14 療療 azole 類 fluconazole 臨 fluconazol ampho-b C krusei C glabrata fluconazole Echinocandins 類 Capsofungin 理 echinocandin 類 echinocandin 類 -1-3 D gluca 行率量 15 Capsofungin 16

Bliss 論量參 ( 見 ) 16 療 17 療更量 16 量 Amphotericin B 0.5-1 mg/kg/day Q 24 hr IV Creatinine ABLC 5 mg/kg/day Q 24 hr IV Creatinine Liposomal Amphotericin 3-5 mg/kg/day Q 24 hr IV Creatinine B Fluconazole 6-12 mg/kg/day Week 1: Q 72 hr Week 2: Q 48 hr Week 3+: Q 24 hr IV, PO Creatinine Voriconazole Capsofungin 6 mg/kg IV load 4 mg/kg IV 50 mg/m2 Q 12 hr Q 24 hr IV, PO IV Calcium Creatinine 1. Rowen JL, Tate JM, for the neonatal candidiasis study group. Management of neonatal candidiasis. Pediatr Infect Dis J 1998;17:1007-1111 2. Huang YC, Lin TY, Lien RI, Chou YH, Kuo CY, Yang PH, Hsieh WS. Fluconazole therapy in neonatal candidemia. Am J of Perinatol 2000;17(8):411-5 3. Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Donowitz LG. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med 2001;345:1660-6 4. Miller MJ. Infectious diseases of the fetus and newborn infant, 5 th ed. Philadelphia: W.B.Saunders;2001:835-9 17

5. Bayley JE, Meyers C, Kleigman RM, et al. Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-flurocytosine in neonates. J Pediatr 1990; 116:791-7 6. Hall JE, Cox F, Karlson K, et al: Amphotericin B dosage for disseminated candidiasis in premature infants. J Perinatol 1987; 7:194-8 7. Serra G, Mezzano P, Bonacci W: Therapeutic treatment of systemic candidiasis in newborns. J Chemother 1991;3:240-4 8. Kamitsuka MD, Nugent NA, Conrad PD, et al: Candida albicans brain abscesses in a premature infant treated with amphotericin B, flucytosine and fluconazole. Pediatr Infect Dis J 1995;14:329-31 9. Dupont B: Overview of the lipid formulations of amphotericin B. J Antimicrob Chemother 49suppl 2002;1:31-6 10. Scarcella A, Pasquariello MB, Giugliano B, et al: Liposomal amphotericin B treatment for neonata fungal infections. Pediatr Infect Dis J 1998;17:146-8 11. Juster-Reicher A, Leibovitz E, Linder N, et al: Liposomal amphotericin B (Ambisome) in the treatment of neonatal candidiasis in very low birth weight infants. Infection 2000;28:223-6 12. Weitkamp JH, Poets CF, Sievers R, et al. Candida infection in very low birth-weight infants: outcome and nephrotoxicity of treatment with liposomal amphotericin B (AmBisome). Infection 1998;26:11-5 13. Wainer S, Coopet PA, Gouws H, et a. A prospective study of fluconazole therapy in systemic neonatal fungal infection. Pediatr Infect Dis J 1997;16:763-7 14. Walsh TJ, Arguedas A, Driscoll T, et al: Pharmacokinetics of intravenous voriconazole in children after single and multiple dose administration, 41 st Interscience Conference on Antimicrobial Agents and Chemotherapy, 2001 (abstr) 15. Walsh TJ, Adamson PC, Seibel NL, et al: Pharmacokinetics of capsofungin in pediatric patients, 42 nd Interscience Conference on Antimicrobial Agents and Chemotherapy, 2002 (abstr) 16. Bliss JM, Wellington M, Gigliotti F. Antifungal pharmacotherapy for neonatal candidiasis. Seminar Perinatol 2003;27:365-74 17. Eppes SC, Troutman JL, Gutman LT. Outcome of treatment of candidemia in children whose central catheters were removed or retained. Pediatr Infect Dis J 1989; 8:99-104 18