ひとくちメモ/山口英世先生

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1 Epidemiology of antifungal resistance : current status and future perspective Hideyo YAMAGUCHI MCZ MCFG 7 4 MRSA Candida spp. MCZ a B b MCFG P45 4αCYP5 c DNA d CYP5 CYP5,3-D-,3-D-,3-D- a b c P45 P454DM datp-binding casette ABC CDR CDR CDR Teikyo University Institute of Medical Mycology (TIMM) (359 Otsuka, Hachioji, Tokyo)

2 5 6 drug resistance MIC antifungal resistance antibacterial resistance Aspergillus spp. MCFG Cryptococcus neoformans Candida albicans C. albicans 2 Aspergillus fumigatus 3 Candida spp. Aspergillus spp. 9, 4 Candida spp. C. glabrata, C. krusei, C. albicans 6 Candida spp. C. lusitaniae C. guilliermondii 8

3 C. krusei C. glabrata non-albicans Candida 5 MCFG Trichosporon spp. 6, 7 clinical resistance 6 MIC MIC 2 CLSI Clinical Laboratory Standards Institute 99 2 M27-A M27-A3 8 M38-A M38-A2 9 M44- A M44-A2 2 2 In vitro MIC in vivo MIC PK PD Candida spp.,, MCFG 22, 23 in vitro in vivo MIC MIC MIC Cr. neoformans

4 Candida spp. MIC CLSI M27 CLSI M27-S3 22 a MCFG S MIC µg ml S-DD I 8 6 a posaconazole caspofungin anidulafungin b S NSR R b NS 2 24, 25 Candida spp. MIC, µg ml 8 CLSI M38- A2 9 Aspergillus spp. 2µg ml,, 4µg ml A. fumigatus MIC 8µg ml 3, 26 in vitro in vivo 27, 28 CLSI Antifungal Susceptibility Testing Subcommittee of EUCAST ; EUCAST-AFST 29 MIC 3-2 8S 6S 4S 7S 5S 3S RNA 6, 3, 32 P45 4 α - 3 -D- DNA - RNA

5 7S 7 5-7,, 33-6, 3, 34, 35 MRSA - ESBL 35 DNA 36 C. albicans 2 2 C. albicans CDR 37 Candida spp. 99 AIDS C. albicans 38 3 SENTRY Antimicrobial Resistance Surveillance Program SENTRY Program objective A objective B, C objective Dobjective E

6 Candida spp caspofungin ; CAS SENTRY Program ARTEMIS Global Antifungal Susceptibility Program ARTEMIS Program Candida spp ARTEMIS Program SENTRY Program Candida ,75 3 2, , ,448 CAS C. a C. gl a C. p C. t Pfaller et al Pfaller et al 2 39 b Pfaller et al 2 4 C. a. C. albicans ; C.gl. C. glabrata ; C. p. C. parapsilosis ; C.t. C. tropicalis ; C.k. C. krusei ; C.l. C. lusitaniae aclsi M27-A b c d, MIC e MIC µg ml C. k C. l. 7. b c Pfaller et al 22 4 d Messer et al e Messer et al 29 43

7 7 C. albicans, C. parapsilosis C. tropicalis C. glabrata C. krusei 7.2 C. krusei C. glabrata C. krusei C. glabrata CDR 5 C. glabrata 9 C. krusei, 5 53 C. albicans 5 C. glabrata C. krusei C. albicans, C. parapsilosis C. tropicalis C. glabrata ARTEMIS Program SENTRY Program Candida 2, , , ,959 8,97 2,656 CAS a CAS a MCFG a CAS C. a. b b.5 b.2 b 2 c b C. gl C. a. C. albicans ; C.gl. C. glabrata ; C. p. C. parapsilosis ; C.t. C. tropicalis ; C.k. C. krusei ; C.gu. C. guilliermondii ; C.l. C. lusitaniae a MIC 2µg ml bclsi M27-A Etest cclsi M27-A C. p C. t C. k C. gu C. l Pfaller et al ARTEMIS Program Pfaller et al ARTEMIS Program Pfaller et al ARTEMIS Program Pfaller et al Pfaller et al Pfaller et al 26 49

8 C. krusei 2 4 C. albicans, C. parapsilosis C. tropicalis C. krusei 7.7 C. glabrata 3 longitudinal study ARTEMIS Program 46 JAS Program Candida spp. ARTEMIS Program JAS Program 2 Candida Candida C. albicans ARTEMIS Program JAS Program C. glabrata ARTEMIS Program JAS Program C. parapsilosis ARTEMIS Program JAS Program C. tropicalis ARTEMIS Program JAS Program C. krusei ARTEMIS Program JAS Program C. guilliermondii ARTEMIS Program JAS Program C. lusitaniae ARTEMIS Program JAS Program 6.7 ARTEMIS Program 25,44 JAS Program,486

9 , 57 C. glabrata in vitro 58 6 C. krusei in vitro 57 C. krusei 6 63 C. krusei CYP5 64, 65 C. krusei C. glabrata SENTRY Program 2 C. krusei C. tropicalis C. krusei Candida spp. C. albicans Cr. neoformans 66 C. albicans 5 CLSI Candida spp Cr. neoformans , 7 C. krusei 5 7, 72 Candida spp SENTRY Program 43 C. albicans Candida spp. C. krusei 6.9 Trichosporon spp. C. lusitaniae 73, 75 C. lusitaniae 76 CLSI M27 CLSI M44 Etest 77 C. krusei C. lusitaniae C. glabrata 78 CAS, MCFG anidulafungin 3 3 Candida spp.

10 48, 49, 79, C. albicans, C. glabrata, C. tropicalis, C. krusei, C. lusitaniae C. parapsilosis C. guilliermondii Candida spp. 84, , C. guilliermondii C. parapsilosis Candida spp. C. albicans, C. glabrata, C. krusei 78, 82, 83, in vitro in vivo 9 SENTRY Program 3 38, 4, 42 ARTEMIS Program 48 SENTRY Program ARTEMIS Program 2 4 ARTEMIS Program Taiwan Surveillance of Antimicrobial Resistance of Yeasts TSARY 92, 93 Candida spp , Japan Invasive Mycosis Surveillance JIMS study group Candida spp ,,,,, MCFG

11 Japan Antifungal Surveillance JAS Program ,56 Candida spp.,486 2 JIMS JAS Program C. albicans, C. parapsilosis C. tropicalis.8,.8, 3.2 vs..2, 4.6,.4,.8, 4.8 vs..2,,.5 Candida , ,448 CAS Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis Candida Candida spp Candida spp Pfaller et al ARTEMIS Program Pfaller et al 2 4 ARTEMIS Program Messer et al SENTRY Program Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis ,329 C. albicans C. glabrata C. tropicalis Pfaller et al ARTEMIS Program C. albicans C. glabrata C. tropicalis

12 Candida MCFG MCFG MCFG MCFG MCFG C. a. C. gl. C. p. C. t. C. k. C. gu. C. l MCFG MCFG , a Takakura et al Japan Invasive Mycosis Surveillance JIMS 3 C. a. C. albicans ; C.gl. C. glabrata ; C. p. C. parapsilosis ; C.t. C. tropicalis ; C.k. C. krusei ; C.gu. C. guilliermondii ; C.l. C. lusitaniae a MIC CLSI M27-A MCFG 24 b b) Japan Antifungal Surveillance JAS Program

13 5 C. glabrata 5.2 vs vs. 2. C. krusei 53.8 vs. 59 vs ARTEMIS Program C. glabrata ARTEMIS Program 5 Candida spp. C. krusei 5 C. albicans C. tropicalis 98 JIMS JAS Program 3 C. albicans.4 vs..2, C. parapsilosis.8 vs., C. tropicalis 4.8 vs..5 2 C. glabrata 56.3 vs. 4.3 C. krusei 38.5 vs. 6.9 JIMS JAS Program C. glabrata C. krusei, MCFG 3 3 JIMS 8 C. tropicalis MCFG JAS Program 3,, ARTEMIS Program 2 C. glabrata C. krusei 57 93

14 , Aspergillus spp. Candida spp. Scedosporium apiospermum Aspergillus terreus A. terreus A. fumigatus A. flavus Aspergillus spp. A. fumigatus b 6, 7 A. fumigatus Aspergillus A. lentulus 6 Aspergillus in vitro A. fumigatus 3, 8, , 3 3 A. fumigatus in vitro in vivo 4 posaconazole ravuconazole isavuconazole A. fumigatus 26 Candida spp. Aspergillus spp. A. fumigatus 43, 54 56, Aspergillus spp. 45 non-fumigatus Aspergillus spp. A. niger 24, A. versicolor 4 A. fumigatus 553 SENTRY Program 43 A. fumigatus 49 3 A. fumigatus JAS Program A. fumigatus 26 A. fumigatus A. terreus A. fumigatus Aspergillus spp. Candida spp. A. fumigatus

15 Aspergillus spp. A. fumigatus A. fumigatus A. flavus A. niger A. terreus A. versicolor Aspergillus spp SENTRY Program 49 A. fumigatus A. fumigatus 3 2 A. fumigatus A. fumigatus A. fumigatus Pfaller et al 28 5 A. flavus A. niger 24 A. terreus A. versicolor 4 Aspergillus spp Messer et al Verweij et al 22 6 Dannaoui et al JAS Program Candida spp. Aspergillus spp. 2 3 MIC 4 HAART high active antiretroviral therapy

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