편집순서 1 : 겉표지 학술연구용역사업최종결과보고서 과 국문과제명 제 영문과제명 명 주 의 ( 주의내용기재 ) 2 0 주관연구기관 : ( 글 14 point 고딕체 ) 질병관리본부 질병관리본부 - 1 -
주의내용 주 의 1. 이보고서는질병관리본부에서시행한학술연구용역사업의최종결 과보고서입니다. 2. 이보고서내용을발표할때에는반드시질병관리본부에서시행한 학술연구용역사업의연구결과임을밝혀야합니다. 3. 국가과학기술기밀유지에필요한내용은대외적으로발표또는공개 하여서는아니됩니다. - 2 -
편집순서 2 : 제출문 질병관리본부학술연구용역사업최종결과보고서 과제명 항진균제내성실태및전파기전연구 수행기관 / 연구책임자 전남대학교병원 / 신종희 발주부서 약제내성과 - 3 -
210 mm 297 mm ( 일반용지 60g/ m2 ( 재활용품 )) 편집순서 3 : 목차 목 차 Ⅰ. 연구개발결과요약문 ( 한글 ) -------------------------------------- 1 ( 영문 ) -------------------------------------- 2 Ⅱ. 학술연구용역사업연구결과 제1장최종연구개발목표 -------------------------------------- 3 제2장최종연구개발내용및방법 ------------------------------- 6 제3장최종연구개발결과 -------------------------------------- 11 제4장연구결과고찰및결론 -------------------------------------- 35 제5장연구성과및활용계획 -------------------------------------- 38 제6장기타중요변경사항 -------------------------------------- 40 제7장연구비사용내역 -------------------------------------- 41 제8장참고문헌 -------------------------------------- 44-1 -
편집순서 4 : 요약문 과제명 중심단어 진균, 칸디다, 항진균제, 항진균제감수성검사, 항진균제내성, 전파기전 주관연구기관전남대병원주관연구책임자신종희연구기간 2012. 3. 16-2012. 12. 15-1 -
편집순서 5 : 요약문 ( 영문 ) Title of Project Fungi, Candida, Antifungal Agents, Antifungal Susceptibility Testing, Key Words Antifungal Resistance, Chonnam National University Institute Project Leader Jong Hee Shin Hospital Project Period 2012. 3. 16-2012. 12. 15. - 2 -
편집순서 6 : 총괄연구과제의연구결과 학술연구용역사업연구결과 Ÿ Ÿ Ÿ Ÿ Ÿ Ÿ Ÿ - 3 -
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Species C. albicans C. parapsilosis C. tropicalis Antifungal agent Test method a New CBPs (ug/ml) b ECVs (ug/ml) b S SDD (I) R WT Non-WT Amphotericin 24h-CLSI NA NA NA <2 >2 Amphotericin EUCAST <1 NA >1 NA NA Fluconazole 24h-CLSI <2 4 >8 <0.5 >0.5 Fluconazole EUCAST <2 4 >8 <1 >1 Voriconazole 24h-CLSI <0.125 0.25-0.5 >1 <0.03 >0.03 Voriconazole EUCAST <0.125 NA >0.125 <0.125 >0.125 Caspofungin 24h-CLSI <0.25 0.5 >1 <0.125 >0.125 Caspofungin EUCAST NA NA NA NA NA Micafungin 24h-CLSI <0.25 0.5 >1 <0.03 >0.03 Micafungin EUCAST NA NA NA NA NA Amphotericin 24h-CLSI NA NA NA <2 >2 Amphotericin EUCAST <1 NA >1 NA NA Fluconazole 24h-CLSI <2 4 >8 <2 >2 Fluconazole EUCAST <2 4 >8 <2 >2 Voriconazole 24h-CLSI <0.125 0.25-0.5 >1 <0.125 >0.125 Voriconazole EUCAST <0.125 NA >0.125 <0.125 >0.125 Caspofungin 24h-CLSI <2 4 >8 <1 >1 Caspofungin EUCAST NA NA NA NA NA Micafungin 24h-CLSI <2 4 >8 <4 >4 Micafungin EUCAST NA NA NA NA NA Amphotericin 24h-CLSI NA NA NA <2 >2 Amphotericin EUCAST <1 NA >1 NA NA Fluconazole 24h-CLSI <2 4 >8 <2 >2 Fluconazole EUCAST <2 4 >8 <2 >2 Voriconazole 24h-CLSI <0.125 0.25-0.5 >1 <0.06 >0.06 Voriconazole EUCAST <0.125 NA >0.125 <0.125 >0.125 Caspofungin 24h-CLSI <0.25 0.5 >1 <0.125 >0.125 Caspofungin EUCAST NA NA NA NA NA Micafungin 24h-CLSI <0.25 0.5 >1 <0.125 >0.125-9 -
C. glabrata Micafungin EUCAST NA NA NA NA NA Amphotericin 24h-CLSI NA NA NA <2 >2 Amphotericin EUCAST <1 NA >1 NA NA Fluconazole 24h-CLSI NA <32 >64 <32 >32 Fluconazole EUCAST NA NA NA <32 >32 Voriconazole 24h-CLSI NA NA NA <0.5 >0.5 Voriconazole EUCAST NA NA NA 1 >1 Caspofungin 24h-CLSI <0.125 0.25 >0.5 <0.125 >0.125 Caspofungin EUCAST NA NA NA NA NA Micafungin 24h-CLSI <0.06 0.125 >0.25 <0.03 >0.03 Micafungin EUCAST NA NA NA NA NA C. guilliermondii C. krusei Amphotericin 24h-CLSI NA NA NA <2 >2 Amphotericin EUCAST NA NA NA NA NA Fluconazole 24h-CLSI NA NA NA <8 >8 Fluconazole EUCAST NA NA NA NA NA Voriconazole 24h-CLSI NA NA NA <0.25 >0.25 Voriconazole EUCAST NA NA NA NA NA Caspofungin 24h-CLSI <2 4 >8 <2 >2 Caspofungin EUCAST NA NA NA NA NA Micafungin 24h-CLSI <2 4 >8 <2 >2 Micafungin EUCAST NA NA NA NA NA Amphotericin 24h-CLSI NA NA NA <2 >2 Amphotericin EUCAST <1 NA >1 NA NA Fluconazole 24h-CLSI NA NA NA 5 0 Fluconazole EUCAST NA NA NA <128 >128 Voriconazole 24h-CLSI <0.5 0.5 >1 5 0 Voriconazole EUCAST NA NA NA <1 >1 Caspofungin 24h-CLSI <0.25 1 >2 <0.25 >0.25 Caspofungin EUCAST NA NA NA NA NA Micafungin 24h-CLSI <0.25 0.5 >1 <0.125 >0.125 Micafungin EUCAST NA NA NA NA NA b Adapted from references (4, 6, 7, and 12) Abbreviations: NA, not available. - 10 -
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Species Blood CSF Peritoneal fluid % of isolates of yeast species Pleural Other total fluid fluids C. albicans 1,354 (36.3) 16 (22.9) 255 (51.7) 87 (62.6) 478 (58.5) 2,190 (41.7) C. parapsilosis 844 (22.6) 8 (11.4) 46 (9.3) 7 (5) 28 (3.4) 933 (17.8) C. glabrata 589 (15.8) 1 (1.4) 99 (20.1) 14 (10.1) 51 (6.2) 754 (14.4) C. tropicalis 557 (14.9) 1 (1.4) 45 (9.1) 9 (6.5) 52 (6.4) 664 (12.7) Cryp. neoformans 23 (0.6) 34 (48.6) 1 (0.2) 0 (0) 0 (0) 58 (1.1) C. guilliermondii 48 (1.3) 0 (0) 0 (0) 1 (0.7) 2 (0.2) 51 (1) C. lusitaniae 26 (0.7) 0 (0) 8 (1.6) 1 (0.7) 6 (0.7) 41 (0.8) Trichosporon spp 26 (0.7) 0 (0) 6 (1.2) 0 (0) 0 (0) 32 (0.6) C. krusei 20 (0.5) 0 (0) 5 (1) 1 (0.7) 1 (0.1) 27 (0.5) C. utilis 26 (0.7) 0 (0) 0 (0) 1 (0.7) 0 (0) 27 (0.5) C. haemulonii 17 (0.5) 0 (0) 3 (0.6) 0 (0) 4 (0.5) 24 (0.5) S. cerevisiae 22 (0.6) 0 (0) 0 (0) 0 (0) 2 (0.2) 24 (0.5) C. pelliculosa 14 (0.4) 1 (1.4) 0 (0) 2 (1.4) 3 (0.4) 20 (0.4) Cryptococcus spp 12 (0.3) 4 (5.7) 0 (0) 0 (0) 2 (0.2) 18 (0.3) C. intermedia 15 (0.4) 0 (0) 0 (0) 0 (0) 0 (0) 15 (0.3) C. lipolytica 9 (0.2) 2 (2.9) 1 (0.2) 0 (0) 0 (0) 12 (0.2) C. famata 7 (0.2) 0 (0) 3 (0.6) 0 (0) 1 (0.1) 11 (0.2) Rhodotorula spp 5 (0.1) 0 (0) 2 (0.4) 0 (0) 1 (0.1) 8 (0.2) Kodamea spp 6 (0.2) 0 (0) 0 (0) 0 (0) 0 (0) 6 (0.1) R. mucilaginosa 4 (0.1) 0 (0) 0 (0) 0 (0) 0 (0) 4 (0.1) C. sphaerica 2 (0.1) 0 (0) 0 (0) 1 (0.7) 0 (0) 3 (0.1) Pichia ohmeri 2 (0.1) 0 (0) 0 (0) 0 (0) 0 (0) 2 (0) C. kefyr 2 (0.1) 0 (0) 0 (0) 0 (0) 0 (0) 2 (0) C. pulcherrima 1 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (0) Malassezia spp. 1 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (0) Non-albicans 0 (0) 0 (0) 0 (0) 0 (0) 110 (13.5) 110 (2.1) Candida spp. 33 (0.9) 0 (0) 8 (1.6) 2 (1.4) 27 (3.3) 70 (1.3) Other yeasts 64 (1.7) 3 (4.3) 11 (2.2) 13 (9.4) 49 (6) 140 (2.7) Total 3,729 70 493 139 817 5,248-14 -
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Species No. of patients with candidemia in each hospital A B C D E F F H I J K L Total no. (%) C. albicans 28 19 32 82 26 34 14 12 31 22 14 51 365 41.2 C. tropicalis 13 8 11 32 4 15 9 14 15 6 5 25 157 17.7 C. glabrata 16 16 27 11 5 7 6 5 7 5 36 141 15.9 C. parapsilosis 13 18 22 12 30 2 10 17 7 7 22 160 18.1 C. krusei 2 1 1 3 7 0.8 C. famata 1 1 0.1 C. guilliermondii. 3 2 1 5 2 1 14 1.6 C. haemulonii 1 1 2 0.2 C. lusitaniae 3 2 1 1 1 1 9 1.0 C. lipolytica 1 1 2 0.2 C. intermedia 2 1 3 0.3 C. pelliculosa 1 2 2 1 6 0.7 C. pulcherrima 1 1 0.1-18 -
C. sphaerica 1 1 0.1 C. utilis 1 2 1 0 4 0.5 Other species 3 3 2 2 2 12 1.4 Total 41 62 86 171 61 91 33 44 76 45 34 141 885 100 0.19 0.15 0.24 0.25 0.28 0.28 0.12 0.11 0.21 0.13 0.12 0.16 0.19 1.86 1.50 2.38 2.50 2.78 2.76 1.24 1.14 2.08 1.30 1.21 1.55 1.86 ( 가 ) 항진균제감수성검사대상균주 Table 8은항진균제감수성검사가실시된총 1,582주의균종과검체를나타낸것이다. 2011년국내 10개병원의혈액배양에서분리된 526주와. includes C. intermedia (2 isolates), C. llipolytica (1 isolate), C. melibiosica (1 isolate), C. kefyr (1 isolate), and C. orthopsilosis (1 isolate) isolates. - 19 -
( CLSI M27-A3법에의해 24시간법으로판정한칸디다 1,056주의 amphotericin B, fluconazole, voriconazole, caspofungin 및 micafungin MIC는각각 0.06-1 μg/ml, 0.125-64 μg/ml, 0.03-2 μg/ml, 0.015-0.5 및 0.007-4 μg/ml이었다. EUCAST에의한결과도매 a. 즉, V 다. - 20 -
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( 가 ) CLSI법에의한항진균제감수성검사성적기존의 CLSI CBP 기준에의해칸디다중 fluconazole에내성및약용량의존감수성을보인균주는각각 1.0% (11주) 및 2.4% (25주) 인반면, 개정된 CBP가적용이가능한균종에대해서 fluconazole에내성및약용량의존감수성은각각 1.8% (18주) 및 15.6% (152주) 이었다. 기존의 CLSI 기준에의해칸디다중 voriconazole에내성및약용량의존감수성을보인균주는없는반면, 개정된 CBP에의해서는각각 0.1% (1주) 및 0.4% (3주) 이었다. Echinocandin 항진균제에대해서는기존의 CLSI 기준에의해 micafungin 내성 0.1% (1주) 뿐인반면, 개정된 CBP에의해서는 micafungin 내성 0.1% (1주) 에추가하여중간내성인균주가 caspofungin 1주, micafungin 2주가검출되었다 (Table 11). - 22 -
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a 24h-CLSI, the CLSI broth microdilution method read at 24 h; EUCAST, broth microdilution method. EA, essential agreement (± 2log2 dilutions) between EUCAST and CLSI MICs. C includes C. lusitaniae (3 isolates), C. intermedia (2 isolates), C. llipolytica (1 isolate), C. melibiosica (1 isolate), C. heamulonii (1 isolate) and C. orthopsilosis (1 isolate) isolates. - 30 -
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Fig. 1. Correlation between antifungal use and fluconazole resistance in bloodstream isolates of Candida species. +0.7 +1.0: strong positive correlations. F - 34 -
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5.1 활용성과 과제명 과제책임자 신종희 / 전남대학교병원 / 진단검사의학 번호논문제목저자명저널명집 ( 권 ) 페이지 Impact factor 1 2 국내 / 국외 SCI여부 번호발표제목발표형태발표자학회명연월일발표지 1 2 Changing Distribution of Yeast Species Isolated from Sterile and Nonsterile Sites in Korea 새로운 CLSI 기준에 의한국내혈류감염 칸디다의항진균제 내성현황및항진균제 사용량과의연관성 포스터신종희외 11 명 대한진단검사 학회추계 학술대회 포스터구연신종희외 7 명대한감염학회추계학술대회 2012,10,1 5 2012.11.0 1 Ann Lab Med 2012:32:S8 2. 2012 년 대한감염학 회추계학술 대회초록집 : 107p 국내 / 국제 국내 국내 번호출원 / 등록 1 2 특허명출원 ( 등록 ) 인출원 ( 등록 ) 국출원 ( 등록 ) 번호 IPC 분류 기타관련정책에활용예를구체적으로기술함. - 38 -
타연구및차기연구에활용된예를구체적으로기술함. 언론홍보및대국민교육내용, 일자등을간략히기술함. 임상시험, 관련 DB 구축, 워크샾또는심포지움개최등의경우구체적으로기술함. 5.2 활용계획 - 39 -
12 개병원중 1 개병원에서병원내부사정으로인하여 2011 년도항진균제사용량조사가되지못 하였음 기타특이사항없음 - 40 -
7.1 연구비사용내역 1,471,353 6,267,849 23,938,015-2.1% 9.1% 34.7% - 602,000 0.9% 550,000-32,690,,833 - - - - 366,000 0.9% - 47.4% - - - - 0.5% 3,113,950-4.5% - 69,000,000 100.0% - 41 -
7.2 연구분담표 - 42 -
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