Epidemiology of antifungal resistance : current status and future perspective Hideyo YAMAGUCHI 2 4 6 4 9 4 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 CDR2 92-395 359 Teikyo University Institute of Medical Mycology (TIMM) (359 Otsuka, Hachioji, Tokyo)
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
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
Candida spp. MIC CLSI M27 CLSI M27-S3 22 a MCFG S 8.25 4 2 MIC µg ml S-DD 6 32.25.5 I 8 6 a posaconazole caspofungin anidulafungin b S NSR R 64 4 32 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
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 997 2 objective A objective B, C objective Dobjective E
997 26 27 Candida spp. 6 38 43 caspofungin ; CAS 997 2 4 4 4 SENTRY Program ARTEMIS Global Antifungal Susceptibility Program ARTEMIS Program Candida spp. 2 39 27 ARTEMIS Program 2 44 2 22 45 997 25 46 3 47 49 997 27 SENTRY Program Candida 997 36 998 328 997 998 999 997 2,75 3 2,47 4 23,397 26 27,448 CAS C. a..6.6. 2.2 2 2 2 3 5 2.4.3.8.3 2. C. gl. 8.7 36.9 5.2 32.8 52 9 37 5 7 4 27 3 92 94 5 2. 73.7.4 69.8 a C. p. 2 36 37.4.7 2..3.4.4 C. t. 4.2 3.6 3 3 3 38.3 3.3 9.2 3.8 4.5.9 Pfaller et al 998 38 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 4 2 5 6 64 65 d, MIC e MIC µg ml C. k. 66.6 8 9 6 74. 59.3 55.6 7.2 2.7 3.4 6.9 3.4 C. l. 7. b c Pfaller et al 22 4 d Messer et al 26 42 e Messer et al 29 43
7 C. albicans, C. parapsilosis C. tropicalis 3 2 3.6 4.4 C. glabrata 5.2 5.8 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.6 2.3.3 4.2 C. glabrata 32.8 69.8 ARTEMIS Program SENTRY Program Candida 2,586 2 22 3,932 997 25 25,329 2 24 24 25 3,959 8,97 2,656 CAS a CAS a MCFG a CAS C. a. b b.5 b.2 b 2 c b C. gl. 7 4 3 5 9 4 5.8. 54 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. 3.6.9 3 C. t. 4.4 5.8 2 4 C. k. 44 63 3 77.8 7.7 43 C. gu..7 5.2 93 52 C. l. 4 4 2 4.7 2. 2 4 7 Pfaller et al 23 44 ARTEMIS Program Pfaller et al 24 45 ARTEMIS Program Pfaller et al 27 46 ARTEMIS Program Pfaller et al 23 47 Pfaller et al 26 48 Pfaller et al 26 49
C. krusei 2 4 C. albicans, C. parapsilosis C. tropicalis.2.9 5.8C. krusei 7.7 C. glabrata 3 longitudinal study ARTEMIS Program 46 JAS Program 54 56 Candida spp. ARTEMIS Program 46 54 56 JAS Program 2 Candida Candida 997 2 2 22 23 24 25 C. albicans ARTEMIS Program.9..8.5..4..6.5.6.5 JAS Program.6.6.6 C. glabrata ARTEMIS Program 9.2 8.3 9.8 4.7 8.5 6.9.5 4.3.4 5.2 9.6 JAS Program 3.8 2.3 3. 2.2.. 7.5 9.3.9 C. parapsilosis ARTEMIS Program 2.5 4.2.9 2.9 2.3 3..5 3.3.9 4.2.9 JAS Program C. tropicalis ARTEMIS Program 3.6 3. 4.7 6.6 8. 5. 6.7 3.5 4.9 3.8 4.5 JAS Program.8 3.5.8 3.5 4.3 2.2 2.2 C. krusei ARTEMIS Program 65.8 7.4 8. 78.9 6. 8.2 8. 78. 8.3 79.2 7.9 JAS Program 57 93 4 4 C. guilliermondii ARTEMIS Program 2.5.7 4.2.5 5.5 8. 4.6. 5. 4.5 6.5 JAS Program C. lusitaniae ARTEMIS Program 2.9 6.6 2.8 4.6.6 2.4.9 4.8.4 6.2 3. JAS Program 6.7 ARTEMIS Program 25,44 JAS Program,486
997 25 8.5, 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 55.6 97 Candida spp. C. albicans Cr. neoformans 66 C. albicans 5 CLSI Candida spp. 2 67 Cr. neoformans 2 68 69, 7 C. krusei 5 7, 72 Candida spp. 26 27 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.
48, 49, 79, 8 9 8 83 C. albicans, C. glabrata, C. tropicalis, C. krusei, C. lusitaniae C. parapsilosis C. guilliermondii Candida spp. 84, 85 2 86 43, 47 49 C. guilliermondii C. parapsilosis Candida spp. C. albicans, C. glabrata, C. krusei 78, 82, 83, 87 9 28 in vitro in vivo 9 SENTRY Program 3 38, 4, 42 ARTEMIS Program 48 SENTRY Program ARTEMIS Program 2 4 ARTEMIS Program 5 2 24 Taiwan Surveillance of Antimicrobial Resistance of Yeasts TSARY 92, 93 Candida spp. 54 56, 94 3 2 Japan Invasive Mycosis Surveillance JIMS study group 99 56 2 22 Candida spp. 535 6,,,,, MCFG
Japan Antifungal Surveillance JAS Program 54 56 2 25 3,56 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 997 36 997 999,75 26 27,448 CAS Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis Candida Candida spp. 2.5.6 2.4.3 3.3 2.4 Candida spp. 4 2.3.8.4 2 Pfaller et al 998 38 ARTEMIS Program Pfaller et al 2 4 ARTEMIS Program Messer et al 29 45 SENTRY Program Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis..8 3.3 4.8.5 Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis 4.3 3.2.8 3.8 2.9.8 3.3 4.8 4.7.2 8.3 Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis 8.7.5 28.6 4. 2.9 8.2 5. 5.6 2. 2.8 Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis 35. 2.7 97.7 56.6 37.7 3.4 2.4 9.9 7. 33.9 27.7.9 94.7 56.6 27.8 Candida spp. C. albicans C. glabrata C. parapsilosis C. tropicalis 2..3.7 9..7.6 7. 997 25 25,329 C. albicans C. glabrata C. tropicalis 2.4 4. 3. 2.4 4. 3..2 6. 2.6.6 9. 2.9.9 3.5 8. Pfaller et al 27 46 ARTEMIS Program C. albicans C. glabrata C. tropicalis.9 9.6 4.4.9 9.6 4.4. 9.9 3.5.3 9. 2.6.9 7.7 4.7
Candida 99 995 2 74 995 996 285 998 97 994 2 MCFG 996 2 38 MCFG 2 22 56 535 MCFG 22 23 92 MCFG 23 24 6 665 MCFG C. a. C. gl. C. p. C. t. C. k. C. gu. C. l. 3..4.3.9.8 3.5 3.5 56 67.9 22 24 2 4 MCFG 999 25 57 MCFG 7 7 7 7 7 7 7 9 9 9 2 25,486.2 4.6 2.3 59.2 4.3 3. 6.9.2 2..5 6.9.6.6 2.3 5 2 4 85 25 75.. 44.8 8.6 94 95 96 98 a Takakura et al 24 99 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 24 48 MIC CLSI M27-A3 24 48 MCFG 24 b 3 54 56 5.3 2.4.5 75 5 3.2 8. 4.8 8. 23 3.8 73 7.7 2 4 7. 97 2 b) 24 54 26 55 26 56 Japan Antifungal Surveillance JAS Program
5 C. glabrata 5.2 vs. 4.6 4.2 vs. 2. C. krusei 53.8 vs. 59 vs. 6.9 2 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 54 56 JAS Program 3,, ARTEMIS Program 2 C. glabrata 3.82 22 2.223 7.525 C. krusei 57 93
, Aspergillus spp. Candida spp. Scedosporium apiospermum Aspergillus terreus 4 996 26 A. terreus 48 3 5 A. fumigatus A. flavus Aspergillus spp. A. fumigatus b 6, 7 A. fumigatus Aspergillus A. lentulus 6 Aspergillus in vitro A. fumigatus 3, 8, 9 2 5 2, 3 3 A. fumigatus in vitro in vivo 4 posaconazole ravuconazole isavuconazole A. fumigatus 26 Candida spp. Aspergillus spp. A. fumigatus 43, 54 56, 5 7 77 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 2 2 7 3 JAS Program 54 56 A. fumigatus 26 A. fumigatus A. terreus A. fumigatus Aspergillus spp. Candida spp. A. fumigatus
Aspergillus spp. A. fumigatus 2 26 77 A. fumigatus A. flavus A. niger A. terreus A. versicolor Aspergillus spp. 26 27 SENTRY Program 49 A. fumigatus 945 998 2 7 A. fumigatus 3 2 A. fumigatus 2 25 26 A. fumigatus A. fumigatus Pfaller et al 28 5 A. flavus A. niger 24 A. terreus A. versicolor 4 Aspergillus spp. 2.8 3 7 4 26 Messer et al 29 43 Verweij et al 22 6 Dannaoui et al 24 7 24 54 26 55 29 56 JAS Program Candida spp. Aspergillus spp. 2 3 MIC 4 HAART high active antiretroviral therapy
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