임상검체에서 분리된 아스페르길루스 균주의 Echinocandin에 대한 생체 외 감수성

이진솔,신종희,정숙인,박경화,최현우,조덕,기승정,김수현,신명근,서순팔,양동욱 대한감염학회 2007 감염과 화학요법 Vol.39 No.3

목적 : 최근 소개된 echinocandin계 항진균제는 생체내 및 생체 외에서 아스페르길루스 균종에 대해 강한 항균력을 보인다고 알려져 있다. 이에 저자들은 국내 환자의 임상 검체에서 분리된 아스페르길루스 균주를 대상으로 caspofungin과 micafungin에 대한 생체 외 감수성 검사를 실시하여 보았다. 재료 및 방법 : 임상 검체에서 분리된 아스페르길루스100주(A. fumigatus 32주, A. flavus 26주, A. niger 22주 및 A terreus 20주)를 대상으로 하였다. Caspofungin과 micafungin에 대한 생체 외 감수성 검사는 CLSI broth microdilution법에 준하여 실시하였으며, 동일균주에 대해 amphotericin B 및 itraconazole 감수성 검사를 실시하여 비교하였다. Caspofungin과 micafungin에 대한 감수성 결과는 minimum inhibitory concentrations (MICs)와 minimum effective concentrations (MECs, 현미경 상으로 짧고 변형된 가지를 보이는 약물의 최소 농도)의 두 가지로 판독하여 비교하여 보았다. 결과 : Caspofungin MEC는 0.06-0.5 ㎍/mL사이의 범위이었고 micafungin MEC는 모두 0.03 ㎍/mL 이하로서 두 약제는 아스페르길루스 균종에 관계없이 우수한 생체외 활성을 보였다. Caspofungin과 micafungin MIC값은 대부분의 균주에서 MEC값과 유사하였으나, 각각 5% (5주) 및 4% (4주) 균주에서 16 ㎍/mL로 증가하여 MIC와 MEC의 연관성을 관찰할 수 없었다. 전체 아스페르길루스 균주에 대한 caspofungin과 micafungin MEC_(50)은 각각 0.25 및 ≤0.03 ㎍/mL이었고, 동일 대상 균주의 amphotericin B와 itraconazole의 MIC_(50)은 각각 0.5 및 0.25 ㎍/mL이었다. 아스페르길루스 균주에 대한 caspofungin과micafungin의 MEC는 아스페르길루스 균종에 따라 차이를 보이지 않았다. 결론 : 임상검체에서 분리된 아스페르길루스 균주를 대상으로 caspofungin과 micafungin에 대한 생체 외 항진균제 감수성 시험을 실시한 결과, echinocandin계 항진균제의 항균력이 매우 우수함을 알 수 있었다. Background : Echinocandins are a new class of antifungal agents with potent in vitro and in vivo activities against Aspergillus species. We investigated the in vitro activity of caspofungin and micafungin against Korean clinical Aspergillus isolates. Materials and Methods : A total of 100 clinical isolates of Aspergillus species (32 A. fumigatus, 26 A. flavus, 22 A. niger and 20 A. terreus) were tested. The susceptibilities of caspofungin, micafungin, amphotericin B and itraconazole were established by means of the Clinical and Laboratory Standards Institute (CLSI) M38-A microdilution methods. The results for caspofungin and micafungin were evaluated by using the end points of minimum inhibitory concentrations (MIC) and minimum effective concentration (MEC, the lowest concentration that produces short and aberrant hyphal branchings microsopically). Results : The MEC ranges of caspofungin and micafungin against 100 isolates of Aspergillus species were 0.06 to 0.5 ㎍/mL and ≤0.03 ㎍/mL, respectively. For both echinocandins, MIC values showed similar ranges to MEC in most isolates of Aspergillus spp., but caspofungin and micafungin MIC increased to >16 ㎍/mL unexpectedly, in 5% (5/100) and 4% (4/100) of isolates, respectively, which resulted in the loss of a consistent correlation between the two endpoint readings. The MECC_(50) of all Aspergillus isolates for caspofungin and micafungin were 0.25 and ≤0.03 ㎍/mL, respectively, and the MIC_(50) for amphotericin B and itraconazole were 0.5 and 0.25 ?g/mL, respectively. There were no species-related differences in caspofungin and micafungin MECs for Aspergillus species. Conclusion : This data demonstrates excellent in vitro activity of echinocandins against clinical strains of Aspergillus species.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성

김시현,최수미,권재철,박선희,최정현,유진홍,이성은,조병식,김유진,이석,김희제,민창기,조석구,김동욱,이종욱,민우성,박종원,이동건 대한감염학회 2010 Infection and Chemotherapy Vol.42 No.3

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.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성

김시현,이동건,최수미,권재철,박선희,최정현,유진홍,이성은,조병식,김유진,이석,김희제,민창기,조석구,김동욱,이종욱,민우성,박종원 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

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 12 days, 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.

증례 : 혈액종양 ; Micafungin을 투여받은 백혈병 환자에서 발생한 Trichosporon 감염증

손서영 ( Seo Young Sohn ),노정원 ( Jung Won Noh ),이가연 ( Ga Yeon Lee ),장복순 ( Bok Soon Chang ),김동환 ( Dong Hwan Kim ),장준호 ( Jun Ho Jang ),정철원 ( Chul Won Jung ) 대한내과학회 2009 대한내과학회지 Vol.77 No.5S

T. ashaii 감염증은 주로 혈액 종양 환자에서 항암 치료 후 발생하는 기회감염증으로 치명적인 경과를 취한다. 최근 호 중구 감소성 발열 환자에서 micafungin 사용 후 돌발성 T. ashaii 감염증이 보고된 바 있다. 생체 외 결과에서 T. ashaii는 azole 계통의 새로운 항진균제에 감수성이 있는 것으로 나타났으나 사람에서 발생한 감염증을 효과적으로 치료한 예는 드물다. 본 저자들은 voriconazole을 사용하여 성공적으로 T. ashaii 감염증을 치료한 1예를 경험하여 보고하는 바이다. Micafungin is a recently approved echinocandin with broad spectrum activity against Candida and Aspergillus species. However, this agent has limited activity against a number of fungi, including Trichosporon. We report a case of Trichosporon asahii fungemia in a 65 year old woman with acute myeloid leukemia that developed after 10 days of empirical micafungin therapy. Trichosporonosis was successfully treated with voriconazole and she achieved complete hematologic remission. After consolidation therapy, T. ashaii fungemia redeveloped, despite empirical amphotericin therapy for neutropenic fever. This was also controlled successfully with voriconazole. Because the use of micafungin is expected to increase, due to its effective antifungal activity, the possibility of breakthrough trichosporonosis should be considered in patients receiving micafungin. Voriconazole may be effective in controlling disseminated T. ashaii infection in neutropenic patients. (Korean J Med 77:S1318-S1322, 2009)

Successful Treatment of Catheter Related Blood Stream Infection By Millerozyma farinosa with Micafungin: A Case Report

홍선인,서영선,김현옥,배인규,신종희,조오현 대한감염학회 2018 Infection and Chemotherapy Vol.50 No.4

Millerozyma farinosa (formerly Pichia farinosa) is halotolerant yeast mainly found in food and ubiquitous in the environment. It was a rare yeast pathogen, but it has recently emerged as a cause of fungemia in immunocompromised patients. Optimal therapy for invasive fungal infection by this pathogen remains unclear. We report a case of catheter related blood stream infection caused by M. farinosa in a 71-year-old patient who recovered successfully after removal of the central venous catheter and treatment with micafungin.

칸디다혈증 후 지연 발생한 흉벽 농양 1예

유하나,정창수,정성웅,모인호,송원근,이재갑 대한감염학회 2012 Infection and Chemotherapy Vol.44 No.3

Recently, the incidence of candida infection has increased. Candida species often show hematogenous spread to the kidney, brain, heart, and eyes. And delayed onset of hematogenous spread is relatively rare. A 53-year-old female patient was admitted with left anterior chest pain with swelling and mild fever. She had been treated successfully with fluconazole for candidemia caused by C. albicans eight month ago. On admission chest CT scan revealed multiple subcutaneous abscesses involving the anterior chest. Percutaneous drainage of the abscess was performed. C. albicans was isolated from drained pus. Treatment with fluconazole did not to improve the abscess; therefore, micafungin and voriconazole were administered as a replacement. The patient recovered after 10-week administration.