Japan Antifungal Surveillance Program (3): 2005

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1 Japan Antifungal Surveillance Program (3): ) 1) 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13) 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13) Japan Antifungal Surveillance Program , Candida 541 Candida 15 Aspergillus 18 Candida Candida fluconazole (FLCZ), itraconazole (ITCZ), voriconazole (VRCZ) flucytosine (5-FC) MIC Aspergillus ITCZ VRCZ MIC CLSI M27-A2 Candida C. albicans C. glabrata C. tropicalis C. parapsilosis C. krusei FLCZ, ITCZ, VRCZ C. albicans C. parapsilosis C. tropicalis 5 C. glabrata 7.5, 9.3, 1.9 C. krusei 93, 14, 14 C. krusei FLCZ MIC 5-FC C. tropicalis Candida Trichosporon asahii 8 ( ) 359 TEL: FAX: ynishiya@main.teikyo-u.ac.jp 6 Vol. 19 No

2 (3) 129 A. fumigatus 17 1 ITCZ (MIC, 8 mg/ml) VRCZ (MIC, 0.5 mg/ml) 2 Key words: Candida 1 4) Candida Candida Aspergillus Candida Candida Cryptococcus neoformans Trichosporon asahii 5, 6) Aspergillus fumigatus Aspergillus 7) Japan Antifungal Surveillance Program (JASP) 2001 (i) (ii) BALF (iii) Candida Candida Aspergillus (iv) 2001 Candida MIC NCCLS (CLSI) M27-A 8) fluconazole (FLCZ), traconazole (ITCZ) flucytosine (5-FC) 3 voriconazole (VRCZ) , 10) JASP 11 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) Vol. 19 No

3 Candida Cryptococcus 11) JASP 9, 10) 1) FLCZ, ITCZ, VRCZ 5-FC 4 ITCZ VRCZ 2 MIC FLCZ VRCZ ITCZ 5-FC CLSI M27-A2 12) 2) CLSI M27-A, M27-A2 8, 12) M MOPS (morpholinepropane sulfonic acid; Sigma-Aldrich Co.) 10 N NaOH ph 7.0 RPMI1640 (Sigma-Aldrich Co.) Candida Candida 48 Cryptococcus IC 50 (MIC) trailing growth 12) Candida 24 IC 50 MIC Candida FLCZ, ITCZ 5-FC Rex et al. 13) CLSI 8, 12) (S) MIC 8, mg/ml (R) 64, 1 32 mg/ml CLSI M27 8, 12) C. krusei FLCZ VRCZ ) Pfaller et al. 15) MIC 1 2 mg/ml Pfaller et al. 16) CLSI M27-A3 17) 1 4 mg/ml 3) Aspergillus ) NCCLS (CLSI) M38-P 19) 20) RPMI 1640 (ph 7.0) alamar blue (Alamar Bioscience Inc.) IC 80 MIC MIC I. Table Candida (93.9 ) Candida 8 17 (2.6 ) 2 18 (3.1 ) Aspergillus A. fumigatus 17 A. niger 1 II. Candida Table 1 Candida C. albicans 333 (57.8 ), C. glabrata 107 (18.6 ), C. tropicalis 46 (8.0 ), C. parapsilosis 27 (4.7 ), C. krusei 14 (2.4 ) C. guilliermondii 8 (1.4 ), C. lusitaniae 4 (0.7 ), C. dubliniensis 1 Candida 1 Table 1 59 Candida 57 (97 ) Candida C. albicans 31 (53 ), C. parapsilosis 11 (19 ), C. glabrata 8 (14 ), C. guilliermondii 4 (7 ), C. tropicalis 3 (5 ) C. parapsilosis C. guilliermondii 19 vs. 4.7, 7 vs Vol. 19 No

4 (3) 131 Table 1. Species distribution of Candida, non-candida yeast and filamentous fungus isolates Organism Isolates from all types of specimens Isolates from blood and related specimens Number Number Candida spp C. albicans C. glabrata C. tropicalis C. parapsilosis C. krusei C. guilliermondii C. lusitaniae C. dubliniensis Candida sp. a) Non-Candida yeasts Trichosporon asahii T. montevideense T. mucoides Cryptococcus neoformans C. curvatus Rhodotorula mucilaginosa Pichia ohmeri Geotrichum capitatum Filamentous fungi Aspergillus fumigatus A. niger Total a) Presumed to be a novel Candida species Table 2. Specimen-based number of fungal isolates and frequency of C. albicans Type of specimens No. of all fungal isolates ( ) No. of C. albicans isolates ( ) Sputum, nasal cavity, bronchoalveolar lavage fluid, etc. 296 (51.4) 175 (59.1) Urine 96 (16.7) 49 (51.0) Pus, other exsudates, etc. 74 (12.8) 43 (58.1) Blood, vessel catheter 59 (10.2) 31 (52.5) Body fluid (spinal fluid, ascites, etc.) 21 (3.6) 13 (61.9) Oral cavity, tongue, bile, stool, gastric juice 18 (3.1) 11 (61.1) Biopsy, autopsy 12 (2.1) 11 (91.7) Total 576 (100) 333 (57.8) III. C. albicans Table (51.4 ) 96 (16.7 ) 74 (12.8 ) 59 (10.2 ) C. albicans Vol. 19 No

5 132 Table 3. In vitro susceptibilities of 541 isolate of Candida spp. against fluconazole (FLCZ), itraconazole (ITCZ), voriconazole (VRCZ) and flucytosine (5-FC) Species (no. of isolates) Antifungal agent MIC (mg/ml) a S b R c Range C. albicans (333) FLCZ ITCZ VRCZ FC C. glabrata (107) FLCZ ITCZ VRCZ FC C. tropicalis (46) FLCZ ITCZ VRCZ FC C. parapsilosis (27) FLCZ ITCZ VRCZ FC C. krusei (14) FLCZ ITCZ VRCZ FC C. guilliermondii (8) FLCZ ITCZ VRCZ FC C. lusitaniae (4) FLCZ ITCZ VRCZ FC C. dubliniensis (1) FLCZ ITCZ VRCZ FC Candida sp. (1) FLCZ ITCZ VRCZ FC a 50 and 90 MIC: MIC at which 50 and 90 of isolates, respectively, are inhibited. b Percent susceptible at a MIC of 8 mg/ml (FLCZ), mg/ml (ITCZ), 1 mg/ml (VRCZ), or 4 mg/ml (5-FC). c Percent resistant at a MIC of 64 mg/ml (FLCZ), 1 mg/ml (ITCZ), 4 mg/ml (VRCZ), or 32 mg/ml (5- FC). 10 Vol. 19 No

6 (3) 133 Table 4. In vitro susceptibilities of 17 isolates of non-candida yeasts against four antifungal agents Species (no. of isolates) Antifungal agent a MIC (mg/ml) Range Trichosporon asahii (8) FLCZ ITCZ VRCZ FC T. montevideense (1) FLCZ 2 ITCZ VRCZ FC 64 T. mucoides (1) FLCZ 8 ITCZ 0.25 VRCZ FC 16 Cryptococcus neoformans (3) FLCZ ITCZ VRCZ FC C. curvatus (1) FLCZ 8 ITCZ 0.25 VRCZ FC 1 Rhodotorula mucilaginosa (1) FLCZ ITCZ VRCZ FC Pichia ohmeri (1) FLCZ 8 ITCZ VRCZ FC Geotrichum capitatum (1) FLCZ 8 ITCZ VRCZ FC a Abbreviations are the same as those for Table 3. IV. Candida Candida 9 4 MIC MIC 50,MIC 90 (S) (R) Table 3 C. albicans 333 FLCZ 50 MIC 90 MIC 0.25, 1 mg/ml (S-DD) (MIC: mg/ml) 8, 12) C. albicans ITCZ VRCZ 50 MIC 90 MIC FLCZ 1/15 1/30 ITCZ (MIC: mg/ml) 5 (1.5 ) ITCZ VRCZ 5- FC 6 (1.8 ) 327 (98.2 ) Vol. 19 No

7 134 Non-albicans Candida 8 C. parapsilosis, C. guilliermondii, C. lusitaniae, C. dubliniensis 3 C. albicans C. glabrata, C. tropicalis C. krusei C. glabrata 107 FLCZ ITCZ 8 (7.5 ) 10 (9.3 ) 5 FLCZ ITCZ 2 FLCZ, ITCZ VRCZ 3 C. krusei 14 FLCZ 13 (93 ) MIC 64 mg/ml 2 ITCZ VRCZ 5-FC C. tropicalis 46 3 (6.5 ) non-albicans Candida V. Candida Candida 17 T. asahii 8 C. neoformans (Table 1) Table 4 C. albicans T. asahii FLCZ, ITCZ VRCZ MIC Rhodotorula mucilaginosa Candida 3 MIC 90 C. albicans FC Trichosporon MIC (2 64 mg/ml) MIC (Table 4) VI. Aspergillus Table 5 Aspergillus 2 18 ITCZ VRCZ ITCZ VRCZ MIC A. fumigatus mg/ml mg/ml A. fumigatus 1 VRCZ MIC 0.5 mg/ml MIC ITCZ MIC 8.0 mg/ml ITCZ VRCZ VII. R. mucilaginosa Candida 5 T. asahii MIC 50, MIC 90 (S ) MIC Table 6 C. glabrata FLCZ (88 vs. 42 ) C. guilliermondii ITCZ (0 vs. 25 ) 2 JASP Table 5. In vitro susceptibilities of 18 isolates of Aspergillus spp. against two antifungal agents Species (no. of isolates) Antifungal agent a MIC (mg/ml) Range Aspergillus fumigatus (17) ITCZ VRCZ A. niger (1) ITCZ 0.5 VRCZ 0.5 a Abbreviations are the same as those for Table Vol. 19 No

8 (3) 135 Table 6. Comparison of in vitro susceptibilities to four antifungal agents between isolates from blood and related specimens and those from all other types of specimens Species (no. of isolates) Antifungal agent a 50 MIC (mg/ml)b 90 S c C. albicans (31 d /302 e ) FLCZ 0.25/0.25 1/1 100/99.3 ITCZ 0.016/ / /98.7 VRCZ / / /100 5-FC 0.125/ / /98.0 C. glabrata (8/99) FLCZ 8/16 16/32 88/42 ITCZ 0.25/ /1 13/11 VRCZ 0.25/ /1 100/95 5-FC 0.063/ / /99 C. tropicalis (3/43) FLCZ 4/4 8/4 100/95 ITCZ 0.063/ / /74 VRCZ 0.063/ / /95 5-FC 0.125/ /2 100/91 C. parapsilosis (11/16) FLCZ 0.5/1 2/2 100/100 ITCZ 0.016/ / /100 VRCZ 0.016/ / /100 5-FC 0.063/ / /100 C. guiliermondii (4/4) FLCZ 4/8 4/16 100/75 ITCZ 0.25/ /0.25 0/25 VRCZ 0.125/ / /100 5-FC 0.063/ / /100 T. asahii (1/7) FLCZ 8/4 8/16 ITCZ 0.125/ /0.5 VRCZ 0.063/ / FC 64/16 64/ 64 a Abbreviations are the same as those for Table 3. b 50 and 90 MIC: MICs at which 50 and 90 of isolates, respectively, are inhibited. c Percent susceptible at a MIC of 8 mg/ml (FLCZ), mg/ml (ITCZ), 1 mg/ml (VRCZ), or 4 mg/ml (5-FC). d Number of isolates from blood and related specimens. e Number of isolates from all other types of specimens JASP / Candida 35 (6.1 ) Aspergillus 18 Candida 2 C. albicans non-albicans Candida (61.5 vs ) vs. 41.4, 57.3 vs non-albicans Candida C. glabrata (18.6 ), C. tropicalis (8.0 ), C. parapsilosis (4.7 ), C. krusei (2.4 ) 2 Candida T. asahii (1.1 ) 2 (2.2 ) Vol. 19 No

9 136 C. albicans Candida Candida T. asahii 3 (FLCZ, ITCZ, VRCZ) VRCZ VRCZ 2008 CLSI M27-3A 17) Candida VRCZ MIC (S, 1 mg/ml; S-DD, 2 mg/ml; R, 4 mg/ml) 1 VRCZ 3 2 Pfaller et al. 16) M27-A3 Candida 2 C. glabrata C. krusei C. glabrata FLCZ ITCZ , , 1.1 C. krusei MIC 64 mg/ml (0 ) (57 ) FLCZ (93 ) ITCZ VRCZ 2 ITCZ VRCZ Candida 2 - C. glabrata FLCZ C. guilliermondii ITCZ 8 4 Pfaller et al. 21) Candida FLCZ VRCZ Candida FLCZ, ITCZ 5-FC M27-A 22 33) FLCZ ITCZ 23, 24, 32) FLCZ ITCZ C. albicans, C. glabrata, C. tropicalis, C. krusei C. guilliermondii 10 25, 26, 29, 31) FLCZ ITCZ C. glabrata ITCZ 20 31) 85 33) JASP M27-A2 12) trailing growth M27-A2 12) M27- A 8) trailing growth 1 M27-A2 MIC M27- A VRCZ 1 1 9) C. krusei FLCZ MIC 64 mg/ ml Takakura et al. 30) ) ) ) JASP , Vol. 19 No

10 (3) 137 C. krusei FLCZ 1990 Candida 5-FC 14, 21, 34 51) FLCZ ITCZ 5 C. glabrata C. krusei FLCZ ITCZ C. glabrata 6 42) 30 45) 20 37) 94 45), C. krusei 35 37, 54) , 43, 44, 46), 20 50) ) FLCZ ITCZ C. albicans, C. parapsilosis, C. tropicalis C. glabrata C. krusei JASP FLCZ ITCZ VRCZ 14, 21, 30, 42, 45, 46) C. glabrata C. krusei Candida 5 JASP VRCZ Candida FC Candida JASP Candida FC 23, 24, 26, 29, 31 33, 35 37, 41, 42, 49) Candida 5-FC 5-FC Candida Candida JASP Candida 20 Trichosporon T. asahii Cryptococcus C. neoformans B ITCZ VRCZ micafungin ITCZ Aspergillus in vitro 52 55) in vivo 56, 57) Aspergillus A. fumigatus 19) Aspergillus 46, 58 61) Aspergillus MIC ITCZ VRCZ MIC 1 mg/ml 4 mg/ml 8 mg/ml ITCZ VRCZ MIC 1 mg/ml A. fumigatus 85 93, Aspergillus A. niger A. versicolor 49, 61) MIC 4 mg/ml 8 mg/ml Aspergillus ITCZ 2 5, VRCZ 1 Vol. 19 No

11 138 49, 56, 59, 61) Aspergillus Aspergillus ITCZ MIC 8 mg/ml ITCZ A. fumigatus 1 VRCZ MIC 0.5 mg/ml VRCZ ITCZ Aspergillus 1 ITCZ Candida Candida Aspergillus Candida 1 Candida auris 62) Pfizer Pharmaceuticals, New York Research Grant (Study No.: DIF ) 1) Pfaller, M. A., D. J. Diekema Rare and emerging opportunistic fungal pathogens: concerns for resistance beyond Candida albicans and Aspergillus fumigatus. J. Clin. Microbiol. 42: ) Nucci, M., K. A. Marr Emerging fungal diseases. Clin. Infect. Dis. 41: ) Fridkin, S. K The changing face of fungal infections in health care settings. Clin. Infect. Dis. 41: ) Pfaller, M. A., P. G. Pappas, J. R. Wingard Invasive fungal pathogens: Current epidemiological trends. Clin. Infect. Dis. 43: S3 S14. 5) Perfect, J. R., W. A. Schell The new fungal opportunists are coming. Clin. Infect. Dis. 22(Suppl. 2): S112 S118. 6) Groll, A. H., T. J. Walsh Uncommon opportunistic fungi: New nosocomial threats. Clin. Microbiol. Infect. 7(Suppl. 2): ) p ) National Committee for Clinical Laboratory Standards Reference method for broth dilution antifungal susceptibility testing for yeasts. Approved standard M 27-A. National Committee for Clinical Laboratory Standards, Wayne, Pa. 17(9). 9) Japan Antifungal Surveillance Program (1): : ) 2006 Japan Antifungal Surveillance Program (2): : ) Mannarelli, B. M., C. P. Kurtzman Rapid identification of Candida albicans and other human pathogenic yeasts by using short oligonucletides in a PCR. J. Clin. Microbiol. 36: ) National Committee for Clinical Laboratory Standards Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard, 2nd ed., M27-A2. National Committee for Clinical Laboratory Standards, Wayne, Pa. 22(15). 13) Rex, J. H., M. A. Pfaller, J. N. Galgiani, et al Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro in vivo correlation data for fluconazole, itraconazole, and Candida infections. Clin. Infect. Dis. 24: ) Sheehan, D. J., C. A. Hitchcock, C. M. Sibley Current and emerging azole antifungal agents. Clin. Microbiol. Rev. 12: ) Pfaller, M. A., D. J. Diekema, R. N. Jones, et al International surveillance of bloodstream infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voricona- 16 Vol. 19 No

12 (3) 139 zole of isolates collected from 1997 through 1999 in the SENTRY Antimicrobial Surveillance Program. J. Clin. Microbiol. 39: ) Pfaller, M. A., D. J. Diekema, J. H. Rex, et al Correlation of MIC with outcome for Candida species tested against voriconazole: analysis and proposal for interpretive breakpoints. J. Clin. Microbiol. 44: ) Clinical and Laboratory Standards Institute Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard-third edition (M27-A3). Clinical and Laboratory Standards Institute, Wayne, Pa. 28(14). 18) : ) National Committee for Clinical Laboratory Standards Reference method for broth dilution antifungal susceptibility testing of conidium-forming filamentous fungi; proposed standard. M38-P. National Committee for Clinical Laboratory Standards, Wayne, Pa. 18 (13). 20) Yamaguchi H., K. Uchida, K. Nagino, et al Usefulness of a colorimetric method for testing antifungal drug susceptibilities of Aspergillus species to voriconazole. J. Infect. Chemther. 8: ) Pfaller, M. A., D. J. Diekema, D. L. Gibbs, et al Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2005: An 8.5 -year analysis of susceptibilities of Candida species and other yeast species to fluconazole and voriconazole determined by CLSI standardized disk di#usion testing. J. Clin. Microbiol. 45: ) Furuta, I., Y. Obana, T. Yamazumi, et al The state of isolation and drug sensitivity of Candida species. Acta Med. Kinki Univ. 21: ) 1997 in vitro fluconazole in vitro/in vivo 45: ) 1998 Candida albicans 72: ) : ) : ) : ) : ) 2003 Jpn. J. Antibiotics 56: ) Takakura, S., N. Fujihara., T. Saito, et al National surveillance of species distribution in blood isolates of Candida species in Japan and their susceptibility to six antifungal agents including voriconazole and micafungin. J. Antimicrob. Chemother. 53: ) 2004 Candida 52: ) 2005 Candida in vitro 79: ) : ) Kao, A. S., M. E. Brandt, W. R. Pruitt, et al The epidemiology of candidemia in two United States cities: results of a population-based active surveillance. Clin. Infect. Dis. 29: ) Colombo, A. L., Z. Nakagawa, F. Valdetaro, et al Susceptibility profile of 200 bloodstream isolates of Candida spp. collected from Brazilian tertiary care hospitals. Med. Mycol. 41: ) Tortorano, A. M., A. L. Rigoni, E. Biraghi, et al The European Confederation of Medical Mycology (ECMM) survey of candidemia in Italy: antifungal susceptibility patterns of 261 non-albicans Candida isolates from blood. J. Antimicrob. Chemother. 52: ) Hajjeh, R. A., A. N. Sofair, L. H. Harrison, et al Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J. Clin. Microbiol. 42: ) Marchetti, O., J. Bille, U. Fluckiger, et al Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, Clin. Vol. 19 No

13 140 Infect. Dis. 38: ) Cuenca-Estrella, M., D. Rodriguez, B. Almirante, et al In vitro susceptibilities of bloodstream isolates of Candida species to six antifungal agents: results from a population-based active surveillance programme, Barcelona, Spain, J. Antimicrob. Chemother. 55: ) Almirante, B., D. Rodriguez, B. J. Park, et al Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, Barcelona, Spain, from 2002 to J. Clin. Microbiol. 43: ) Metwally, L., M. J. Walker. V. Coyle, et al Trends in candidemia and antifungal susceptibility in a university hospital in Northern Ireland J. Infect. 55: ) Odds, F. C., M. F. Hanson, A. D. Davidson, et al One year prospective survey of Candida bloodstream infections in Scotland. J. Med. Microbiol. 56: ) Pfaller, M. A., R. N. Jones, G. V. Doern, et al International surveillance of bloodstream infections due to Candida species: frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States, Canada, and South America for the SENTRY Program. J. Clin. Microbiol. 36: ) Pfaller, M. A., R. N. Jones, G. V. Doern, et al Bloodstream infections due to Candida species: SENTRY Antimicrobial Surveillance Program in North America and Latin America, Antimicrob. Agents Chemother. 44: ) Pfaller, M. A., D. J. Diekema, R. N. Jones, et al Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY Antimicrobial Surveillance Program, 1997 to J. Clin. Microbiol. 40: ) Pfaller, M. A., D. J. Diekema, S. A. Messer, et al Activities of fluconazole and voriconazole against 1,586 recent clinical isolates of Candida species determined by broth microdilution, disk di#usion, and E test methods; report form the ARTEMIS global antifungal susceptibility program, J. Clin. Microbiol. 41: ) Pfaller, M. A., D. J. Diekema, S. A. Messer, et al In vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp., including 157 fluconazole-resistant isolates. Antimicrob. Agents Chemother. 47: ) Pfaller, M. A., L. Boyken, R. J. Hollis, et al In vitro susceptibilities of Candida spp. to caspofungin: four years of global surveillance. J. Clin. Microbiol. 44: ) Messer, S. A., R. N. Jones, T. R. Fritsche International surveillance of Candida spp. and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2003). J. Clin. Microbiol. 44: ) Ostrosky-Zeichner, L., J. H. Rex, P. G. Pappas, et al Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States. Antimicrob. Agents Chemother. 47: ) Lortholary, O., E. Dannaoui, D. Raoux, et al In vitro susceptibility to posaconazole of 1,903 yeast isolates recovered in France from 2003 to 2006 and tested by the method of the European Committee on Antimicrobial Susceptibility Testing. Antimicrob. Agents Chemother. 51: ) Chryssanthou, E In vitro susceptibility of respiratory isolates of Aspergillus species to itraconazole and amphotericin B acquired resistance to itraconazole. Scand. J. Infect. Dis. 29: ) Verweij, P. E., M. Mensink, A. J. Rijs, et al In-vitro activities of amphotericin B, itraconazole and voriconazole against 150 clinical and environmental Aspergillus fumigatus isolates. J. Antimicrob. Chemother. 42: ) Dannaoui, E., F. Persat, M. F. Monier, et al In-vitro susceptibility of Aspergillus spp. isolates to amphotericin B and itraconazole. J. Antimicrob. Chemother. 44: ) Dannaoui, E., E. Borel, M. F. Monier, et al Acquired itraconazole resistance in Aspergillus fumigatus. J. Antimicrob. Chemother. 47: ) Denning, D. W., K. Venkateswarlu, K. L. Oakley, et al Itraconazole resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother. 41: ) Dannaoui, E., E. Borel, F. Persat, et al In-vivo itraconazole resistance of Aspergillus fumigatus in systemic murine aspergillosis. EBGA Network. European research group on biotypes and genotypes of Aspergillus fumigatus. J. Med. Microbiol. 48: ) Verweij, P. E., D. T. A., Te Dorsthorst, A. J. M. M. Rijs, et al Nationwide survey of in vitro activities of itraconazole and voriconazole against clinical Aspergillus fumigatus isolates 18 Vol. 19 No

14 (3) 141 cultured between 1945 and J. Clin. Microbiol. 40: ) Gomez-Lopez, A., G. Garcıÿa-E#ron, E. Mellado, et al In vitro activities of three licensed antifungal agents against Spanish clinical isolates of Aspergillus spp. Antimicrob. Agents Chemother. 47: ) Diekema, D. J., S. A. Messer, R. J. Hollis, et al Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J. Clin. Microbiol. 41: ) Pfaller, M. A., S. A. Messer, L. Boyken, et al In vitro survey of triazole crossresistance among more than 700 clinical isolates of Aspergillus species. J. Clin. Microbiol. 46: ) Satoh K., K. Makimura, Y. Hasumi, et al Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol. Immunol. 53: Nationwide Survey of Antifungal Drug Susceptibility of Clinical Fungal Isolates in Japan for the Japan Antifungal Surveillance Program (JASP), 2005 Hideyo Yamaguchi, 1) Yayoi Nishiyama, 1) Katsuhisa Uchida, 1) Choichiro Takahashi, 2) Chieko Kawashima, 3) Mutsumu Hayashi, 4) Sayoko Kawakami, 5) Keiko Adachi, 6) Katsuko Okuzumi, 7) Yoshiki Misawa, 8) Toyoko Oguri, 9) Yukie Okimura, 10) Toshimi Kitazawa, 11) Yoshiko Hori, 12) Masakazu Tosaka 13) (Association of Japan Antifungal Susceptibility Surveillance) 1) Teikyo University Institute of Medical Mycology 2) Yamagata University Hospital 3) Ashikaga Red Cross Hospital 4) Saitama Medical Center Jichi Medical University 5) Teikyo University Hospital 6) Tokyo Metropolitan Geriatric Hospital 7) Dokkyo University Hospital 8) The University of Tokyo Hospital 9) Juntendo University Hospital (Current address: Kameda Medical Center) 10) Shinshu University Hospital 11) Kikkoukai General Hospital Tane Hospital 12) Okayama Saiseikai General Hospital 13) Kumamoto University Hospital As a third nationwide surveillance of the longitudinal Japanese Antifungal Surveillance Program (JASP), a total of 541 Candida isolates, 17 non-candida yeast isolates, and 18 Aspergillus isolates collected in 11 hospitals during 2 months, June and July 2005, were studied for their in vitro antifungal susceptibilities. The rank order of Candida spp. occurrence was as follows: C. albicans (57.8 ), C. glabrata (18.6 ), C. tropicalis (8.0 ), C. parapsilosis (4.7 ) andc. krusei (2.4 ). Percent resistant by using the interpretive breakpoint criteria of CLSI guideline to fluconazole (FLCZ), itraconazole (ITCZ) and voriconazole (VRCZ) was 7.5, 9.3 and 1.9 for C. glabrata and 93, 14 and 14 for C. krusei, respectively. In other Candida spp., isolates resistant to any of the three azoles drugs were not or only infrequently detected. All Candida spp. isolates were favorably susceptible to 5-FC. All of 17 A. fumigatus isolates were susceptible to both ITCZ and VRCZ except one isolate insusceptible only to ITCZ (MIC, 8 mg/ml). These results which extend upon previous finding from JASP reports (2001 to 2003) suggest a changing trend of frequency of resistance for Candida spp. isolates and emphasize the importance of continuing this or a similar type of surveillance. Vol. 19 No