임상검체에서 분리된 아스페르길루스 균주의 Echinocandin에 대한 생체 외 감수성
In Vitro Susceptibilities of Clinical Isolates of Aspergillus Species against Echinocandins
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목 적 : 최근 소개된 echinocandin계 항진균제는 생체 내 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 아스페르길루스 100주(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. 결 과 : Caspofungin MEC는 0.06-0.5 g/mL사이의 범위이었고 micafungin MEC는 모두 0.03 g/mL 이하로서 두 약제는 아스페르길루스 균종에 관계없이 우수한 생체 외 활성을 보였다. Caspofungin과 micafungin MIC값은 대부분의 균주에서 MEC값과 유사하였으나, 각각 5% (5주) 및 4% (4주) 균주에서 16 g/mL로 증가하여 MIC와 MEC의 연관성을 관찰할 수 없었다. 전체 아스페르길루스 균주에 대한 caspofungin과 micafungin MEC50은 각각 0.25 및 ≤0.03 g/mL이었고, 동일 대상 균주의 amphotericin B와 itraconazole의 MIC50은 각각 0.5 및 0.25 g/ mL이었다. 아스페르길루스 균주에 대한 caspofungin과 micafungin의 MEC는 아스페르길루스 균종에 따라 차이를 보이지 않았다. 결 론 : 임상검체에서 분리된 아스페르길루스 균주를 대상으로 caspofungin과 micafungin에 대한 생체 외 항진균제 감수성 시험을 실시한 결과, echinocandin계 항진균제의 항균력이 매우 우수함을 알 수 있었다.
Abstract
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 g/mL and ≤0.03 g/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 g/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 MEC50 of all Aspergillus isolates for caspofungin and micafungin were 0.25 and ≤0.03 g/mL, respectively, and the MIC50 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.
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