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1 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 mg/kg 6-8 不 來說 念 1mg/kg 量 量 療 不 度 14

2 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 Cryptococcus neoformans Coccidiodes immitis Aspergillus species Phycomycetes 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 mg/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

3 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

4 Bliss 論 量 參 ( 見 ) 16 療 17 療 更 量 16 量 Amphotericin B 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: 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): 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: Miller MJ. Infectious diseases of the fetus and newborn infant, 5 th ed. Philadelphia: W.B.Saunders;2001:

5 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: Hall JE, Cox F, Karlson K, et al: Amphotericin B dosage for disseminated candidiasis in premature infants. J Perinatol 1987; 7: Serra G, Mezzano P, Bonacci W: Therapeutic treatment of systemic candidiasis in newborns. J Chemother 1991;3: 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: Dupont B: Overview of the lipid formulations of amphotericin B. J Antimicrob Chemother 49suppl 2002;1: Scarcella A, Pasquariello MB, Giugliano B, et al: Liposomal amphotericin B treatment for neonata fungal infections. Pediatr Infect Dis J 1998;17: 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: 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: 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: 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: 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: