조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성
Efficacy and Safety of Micafungin for Prophylaxis of Invasive Fungal Infection in Hematopoietic Stem Cell Transplantation Recipients
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Background: Micafungin, a potent inhibitor of 1,3-β-D-glucan synthase, is a novel antifungal agent of the echinocandin class. In vitro study showed that micafungin was effective against Aspergillus species as well as Candida species, but clinical data on the prophylactic efficacy against invasive fungal infections (IFIs) other than candidiasis are still lacking. Materials and Methods: We identified 60 consecutive adult hematopoietic stem cell transplantation (HSCT) recipients who received at least 3 doses of micafungin during neutropenic period. Micafungin was started as an alternative in patients who were intolerant or had adverse events (AEs) to primary prophylactic antifungal agents. We retrospectively reviewed the medical records and analyzed the efficacy and safety of micafungin for prophylaxis against IFIs. Results: The patients either had autologous (n=9) or allogeneic (n=51: 1 syngeneic,24 sibling, 26 unrelated donor) HSCT. Itraconazole oral solution (n=58) was the most frequently used first line antifungal agent for prophylaxis and was administered for median 11 days. The most frequent cause of switch to micafungin was vomiting (n=42). The duration of neutropenia and micafungin administration was median 13 and 12days, respectively. A successful outcome was achieved in 45 (75%) patients. Empirical antifungal therapy was initiated in 13 (22%) patients. There were 2 cases (3.3%) of breakthrough fungal infections which comprised a probable invasive pulmonary aspergillosis and a possible invasive fungal sinusitis. There was no case of invasive candidiasis. A total of 53 (88%) patients experienced at least one AE regardless of causality during micafungin administration. The most frequent AEs were hypokalemia, vomiting,diarrhea, and elevated serum aspartate aminotransferase or alanine aminotransferase. Among the aforementioned AEs, only 1 case of diarrhea could be classified as a probable relation with micafungin when causality was assessed. There was no AEs that caused discontinuation of micafungin. Conclusions: Micafungin seems to be a safe and effective agent for prophylaxis of IFIs including aspergillosis as well as candidiasis in HSCT recipients. However, further large,prospective, and randomized comparative studies are warranted for aspergillosis.
Abstract
Background: Micafungin, a potent inhibitor of 1,3-β-D-glucan synthase, is a novel antifungal agent of the echinocandin class. In vitro study showed that micafungin was effective against Aspergillus species as well as Candida species, but clinical data on the prophylactic efficacy against invasive fungal infections (IFIs) other than candidiasis are still lacking. Materials and Methods: We identified 60 consecutive adult hematopoietic stem cell transplantation (HSCT) recipients who received at least 3 doses of micafungin during neutropenic period. Micafungin was started as an alternative in patients who were intolerant or had adverse events (AEs) to primary prophylactic antifungal agents. We retrospectively reviewed the medical records and analyzed the efficacy and safety of micafungin for prophylaxis against IFIs. Results: The patients either had autologous (n=9) or allogeneic (n=51: 1 syngeneic,24 sibling, 26 unrelated donor) HSCT. Itraconazole oral solution (n=58) was the most frequently used first line antifungal agent for prophylaxis and was administered for median 11 days. The most frequent cause of switch to micafungin was vomiting (n=42). The duration of neutropenia and micafungin administration was median 13 and 12days, respectively. A successful outcome was achieved in 45 (75%) patients. Empirical antifungal therapy was initiated in 13 (22%) patients. There were 2 cases (3.3%) of breakthrough fungal infections which comprised a probable invasive pulmonary aspergillosis and a possible invasive fungal sinusitis. There was no case of invasive candidiasis. A total of 53 (88%) patients experienced at least one AE regardless of causality during micafungin administration. The most frequent AEs were hypokalemia, vomiting,diarrhea, and elevated serum aspartate aminotransferase or alanine aminotransferase. Among the aforementioned AEs, only 1 case of diarrhea could be classified as a probable relation with micafungin when causality was assessed. There was no AEs that caused discontinuation of micafungin. Conclusions: Micafungin seems to be a safe and effective agent for prophylaxis of IFIs including aspergillosis as well as candidiasis in HSCT recipients. However, further large,prospective, and randomized comparative studies are warranted for aspergillosis.
참고문헌 (37)
- Mandell GL, "Principles and Practice of Infectious Diseases", pp.3495~ (2005), Elsevier Inc.
- Viscoli C, "Candidemia in cancer patients: a prospective multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of cancer (EORTC)", Clin Infect Dis, 28, pp.1071~1079 (1999)
- Lin SJ, "Aspergillosis case-fatality rate: systematic review of the literature", Clin Infect Dis, 32, pp.358~366 (2001)
- von Eiff M, "Pulmonary aspergillosis: early diagnosis improves survival", Respiration, 62, pp.341~347 (1995)
- Hope WW, "Laboratory diagnosis of invasive aspergillosis", Lancet Infect Dis, 5, pp.609~622 (2005)
- Maertens JA, "Primary antifungal prophylaxis in leukaemia patients", Eur J Cancer, (Suppl 5), pp.43~48 (2007)
- Michallet M, "Approaches to the management of invasive fungal infections in hematologic malignancy and hematopoietic cell transplantation", J Clin Oncol, 27, pp.3398~3409 (2009)
- Kuse ER, "Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial", Lancet, 369, pp.1519~1527 (2007)
- Pappas PG, "Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis", Clin Infect Dis, 45, pp.883~893 (2007)
- van Burik JA, "Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation", Clin Infect Dis, 39, pp.1407~1416 (2004)
- De Pauw B, "Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer", Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC, Clin Infect Dis, pp.2008, 43[DOI]
- "Common Terminology Criteria for Adverse Events v3.0 (CTCAE)"[URL]
- Naranjo CA, "A method for estimating the probability of adverse drug reactions", Clin Pharmacol Ther, 30, pp.239~245 (1981)
- Glucksberg H, "Clinical manifestations of graftversus-host disease in human recipients of marrow from HLA-matched sibling donors", Transplantation, 18, pp.295~304 (1974)
- Lass-Florl C, "The changing face of epidemiology of invasive fungal diseases in Europe", Mycoses, 52, pp.197~205 (2009)
- Pfaller MA, "Epidemiology of invasive candidiasis: a persistent public health problem", Clin Microbiol Rev, 20, pp.133~163 (2007)
- Tortorano AM, "Candidaemia in Europe: epidemiology and resistance", Int J Antimicrob Agents, 27, pp.359~366 (2006)
- Sanz MA, "Epidemiology of invasive fungal infections due to Aspergillus spp. and zygomycetes", Clin Microbiol Infect, 12, pp.2~6 (2006)
- Tomblyn M, "Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective", Biol Blood Marrow Transplant, 15, pp.1143~1238 (2009)
- 이진솔, "임상검체에서 분리된 아스페르길루스 균주의 Echinocandin에 대한 생체 외 감수성", Infection and Chemotherapy, 39(3), pp.151~158 (2007), 대한감염학회
- Denning DW, "Echinocandin antifungal drugs", Lancet, 362, pp.1142~1151 (2003)
- Arikan S, "Comparison of two methods and three end points in determination of in vitro activity of micafungin against Aspergillus spp.", Antimicrob Agents Chemother, 47, pp.2640~2643 (2003)
- Chandrasekar PH, "Micafungin: a new echinocandin", Clin Infect Dis, 42, pp.1171~1178 (2006)
- Cross SA, "Micafungin: a review of its use in adults for the treatment of invasive and oesophageal candidiasis, and as prophylaxis against Candida infections", Drugs, 68, pp.2225~2255 (2008)
- Yoon MJ, "The spectrum of infection in patients with acute leukemia", Korean J Infect Dis, 17, pp.45~52 (1985)
- Choi H, "The spectrum of infection in patients with acute leukemia", Korean J Intern Med, 46, pp.496~504 (1994)
- Choi JH, "Infectious features in patients with acute leukemia", Korean J Infect Dis, 31, pp.217~224 (1999)
- 최수미, "급성 백혈병 환자의 감염양상 : 관해 유도 및 재관해유도 화학요환자군의 비교", Infection and Chemotherapy, 35(2), pp.78~85 (2003), 대한감염학회
- 우현영, "Two Cases of Candida inconspicua Infection in Neutropenic Patients with Acute Leukemia", Infection and Chemotherapy, 38(3), pp.164~168 (2006), 대한감염학회
- 유진홍, "혈액질환 환자에서 조혈모세포 이식과화학요법 후의 침습성 진균감염의 분석", Infection and Chemotherapy, 36(1), pp.40~45 (2004), 대한감염학회
- 최수미, "조혈모세포이식 환자에서 침습성 진균 감염에 대한이트라코나졸 액과 플루코나졸 시럽의 예방 효과 :전향적, 무작위, 비교 임상시험", Infection and Chemotherapy, 37(2), pp.71~78 (2005), 대한감염학회
- Hiramatsu Y, "Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation", Int J Hematol, 88, pp.588~595 (2008)
- Ascioglu S, "Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus", Clin Infect Dis, 34, pp.7~14 (2002)
- Glasmacher A, "An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia", J Antimicrob Chemother, 57, pp.317~325 (2006)
- Harousseau JL, "Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B", Antimicrob Agents Chemother, 44, pp.1887~1893 (2000)
- Sohn HS, "Cost-effectiveness analysis of micafungin versus fluconazole for prophylaxis of invasive fungal infections in patients undergoing hematopoietic stem cell transplantation in Korea", Clin Ther, 31, pp.1105~1115 (2009)
- Schonfeld W, "Costeffectiveness analysis of antifungal prophylaxis in patients undergoing hematopoietic stem cell transplantation", Clin Ther, 30, pp.964~973 (2008)