CORRESPONDENCE

In vitro activity of ravuconazole against (four Mucor spp. and one Fusarium sp.) were unable Zygomycetes, Scedosporium and Fusarium to grow at 35 8C and were tested at 30 8C. Ampho- isolates tericin B MICs were read as complete inhibition of growth (MIC-0), while the MICs were read as a prominent decrease in growth (MIC-2). Against the Zygomycetes, ravuconazole and Ravuconazole (BMS-207147, ER-30346) is a novel were the most active , with with activityagainst Candida species, Cryp- modal MICs of 0.5±2 mg/L against most species tococcus neoformans, aspergilli, dermatophytes and of the Zygomycetes class (Table 1). As reported other ®lamentous fungi [1±3]. The spectrum of previously[9±11] and in the current study,vor- ravuconazole includes yeast species (such as Can- iconazole is inactive against the Zygomycetes, dida krusei and Candida glabrata) that are non-sus- with MICs 16 mg/L against most strains. With ceptible to ¯uconazole. Candida albicans mutants the exception of Cunninghamella spp., against with cumulative resistance to azoles maybe sus- which is inactive, the MICs of ceptible to ravuconazole [4]. amphotericin B against other Zygomycetes strains Non-Aspergillus molds can cause invasive infec- were generally 1 mg/L. All three azoles are tions in immunocompromised patients. While inactive against Mucor strains. Onlyamphotericin azoles, and amphotericin B are B has activityagainst Mucor. active against ®lamentous fungi, their activities With regard to Scedosporium spp., amphotericin against these organisms are species-dependent B was inactive against S. apiospermum and S. pro- [5,6]. In this study, we evaluate the li®cans. The azoles are inactive against S. proli®cans. potencyof ravuconazole, itraconazole, voricona- was the most active (MIC ˆ 0.5 mg/ zole and amphotericin B against 57 mold strains of L) against S. apiospermum, while ravuconazole and Scedosporium or Fusarium spp., or the class Zygo- itraconazole were moderatelyactive (median mycetes. MIC ˆ 2 mg/L). These ®ndings are similar to Strains of Zygomycetes, Scedosporium and Fusar- those reported previouslybyCarrillo and Guarro ium spp. were either from the Bristol-Myers [12], except for voriconazole against S. proli®cans. Squibb culture collection, from the American Type We observed that the voriconazole MIC against S. Culture Collection (Manassas, VA, USA), or kind proli®cans was 16 mg/L, like other azoles, as was gifts from John Rex (Universityof Texas Health con®rmed byother investigators [6,9,13,14]. In Science Center, Houston, TX, USA) or Ana Espi- contrast, Carrillo and Guarro [12] and Meletiadis nel-Ingroff (Medical College of Virginia, Rich- et al. [15] reported that while most azoles were mond, VA, USA). The species belonging to the inactive (MICs > 16 mg/L) against S. proli®cans, class Zygomycetes tested included Rhizopus oryzae voriconazole was much more active (MIC50, (®ve strains), Rhizopus microsporus (one strain), 2 mg/L; MIC90, 4 mg/L) against this species. Absidia corymbifera (eight strains), and Rhizomucor Nonetheless, the azoles have more potent activity pusillus (four strains); these are the most frequent against S. apiospermum than against S. proli®cans. agents of zygomycosis [7]. Cunninghamella berthol- Voriconazole was recentlyFDA-approved for the letiae (®ve strains) and Mucor spp. (seven strains) treatment of S. apiospermum infections. were among the other Zygomycetes strains tested. For the Fusarium spp., azoles had poorer activity The Scedosporium species tested were S. apiosper- against F. oxysporum and F. solani. The azoles mum (three strains) and S. proli®cans (six strains). appeared to be more active against F. verticillioides The Fusarium species evaluated were F. oxysporum (modal MIC  1 mg/L). Itraconazole was the (three strains), F. verticillioides (three strains) and F. least active azole against Fusarium strains, gener- solani (eight strains). allywith MICs > 16 mg/L. Voriconazole was MICs were determined bythe microbroth dilu- moderatelyactive (MICs  8 mg/L) against many tion method, recommended bythe National Com- Fusarium isolates. Voriconazole was more active mittee for Clinical LaboratoryStandards (NCCLS), than ravuconazole against F. solani, though ravu- using inocula of 104 CFU/mL [8]. MICs were conazole appeared to be more active than vorico- read after 48 h (24 h for Rhizopus spp., 72 h for nazole against F. veriticillioides. Voriconazole was S. apiospermum) of incubation at 35 8C. Five strains recentlyapproved bythe FDA for the treatment of

ß 2003 Copyright by the European Society of Clinical Microbiology and Infectious Diseases Correspondence 1251

Table 1 In vitro activity of ravuconazole against Zygomycetes, Scedosporium and Fusarium spp.

Fungal species n Compound MIC (no. of strains)a Modal (median) MICb Zyqomycetes Absidia corymbifera 8 Ravuconazole 1 (2), 2 (3), 4 (2), 8 (1) 2 ltraconazole 1 (3), 2 (3), 4 (1), >16 (1) 1, 2 Voriconazole 16 (1), >16 (7) >16 Amphotericin B 0.5 (3), 1 (5) 1 Cunninghamella spp. 6 Ravuconazole 0.5 (1), 2 (3), 4 (1), >16 (1) 2 ltraconazole 1 (2), 2 (3), >16 (1) 2 Voriconazole 16 (3), >16 (3) >16 Amphotericin B 4 (4), 8 (1), 16 (1) 4 Mucor spp. 7 Ravuconazole 1 (1), 4 (2), >16 (4) >16 ltraconazole 0.5 (1), 4 (1), >16 (5) >16 Voriconazole 16 (1), >16 (6) >16 Amphotericin B 0.5 (1), 1 (6) 1 Rhizopus spp. 6 Ravuconazole 0.25 (1), 0.5 (2), 1 (3) 1 ltraconazole 1 (3), 2 (3) 1, 2 Voriconazole 8 (3), 16 (1), >16 (2) 8 Amphotericin B 1 (5), 4 (1) 1 Rhizomucor spp. 7 Ravuconazole 0.5 (6), 1 (1) 0.5 ltraconazole 0.5 (2), 1 (5) 1 Voriconazole 1 (1), 16 (5), >16 (1) 16 Amphotericin B 0. 2 5 (1), 0.5 (3), 1 (3) 0.5 Scedosporidium spp. Scedosporium apiospermum 3 Ravuconazole 0.25(1), 2 (1), 4 (1) (2) ltraconazole 1 (1), 2 (1), 4 (1) (2) Voriconazole 0.5 (3) 0.5 Amphotericin B 4 (1), 8 (1), >16 (1) (8) Scedosporium prolificans 6 Ravuconazole >16 (6) >16 ltraconazole >16 (6) >16 Voriconazole 16 (5), >16 (1) 16 Amphotericin B 16 (3) >16 (3) >16 Fusarium spp. Fusarium oxysporum 3 Ravuconazole 4 (1), 8 (1), 16 (1) (8) ltraconazole >16 (3) >16 Voriconazole 4 (1), 8 (2) 8 Amphotericin B 2 (3) 2 Fusarium verticellioides 3 Ravuconazole 0.5 (2), >16 (1) 0.5 ltraconazole 1 (2), >16 (1) 1 Voriconazole 1 (2), 8 (1) 1 Amphotericin B 2 (1), 4 (2) 4 Fusarium solani 8 Ravuconazole 8 (1), >16 (7) >16 Itraconazole >16 (8) >16 Voriconazole 4 (1), 8 (5), 16 (1), >16 (1) 8 Amphotericin B 1 (3), 2 (3), 4 (1), >16 (1) 1, 2 aThe MIC values are listed, with the number of strains observed at each MIC concentration (in mg/L) indicated in parentheses. bThe median MIC value (in mg/L) is indicated when no modal MIC exists. serious infections caused by Fusarium spp., includ- against these pathogens. With the variable activity ing F. solani. Amphotericin B had borderline activ- of azoles against Fusarium and Scedosporium spp., ityagainst Fusarium, with MICs 2 mg/L against susceptibilitytesting mayhelp direct therapyfor most strains. infections caused bythese pathogens. In conclusion, none of the antifungal agents evaluated, including amphotericin B, were active B. Minassian, E. Huczko, T. Washo, D. Bonner against all of the mold species tested. While vor- and J. Fung-Tomcà iconazole was inactive against Zygomycetes, ravu- Department of Microbiology, conazole and itraconazole were comparablyactive Bristol-Myers Squibb Company,

ß 2003 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 9, 1250±1252 1252 Clinical Microbiology and Infection, Volume 9 Number 12, December 2003

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