During a 3-year surveillance program (2004 to 2007) in Monterrey, Mexico, 398 isolates of Candida spp. were collected from five hospitals. We established the species distribution and in vitro susceptibilities of these isolates. The species included 127 Candida albicans strains, 151 C . parapsilosis strains, 59 C . tropicalis strains, 32 C . glabrata strains, 11 C . krusei strains, 5 C . guilliermondii strains, 4 C . famata strains, 2 C . utilis strains, 2 C . zeylanoides strains, 2 C . rugosa strains, 2 C . lusitaniae strains, and 1 C . boidinii strain. The species distribution differed with the age of the patients. The proportion of candidemias caused by C . parapsilosis was higher among infants ≤1 year old, and the proportion of candidemias caused by C . glabrata increased with patient age (>45 years old). MICs were calculated following the criteria of the Clinical Laboratory Standards Institute reference broth macrodilution method. Overall, C . albicans , C . parapsilosis , and C . tropicalis isolates were susceptible to fluconazole and amphotericin B. However, 31.3% of C . glabrata isolates were resistant to fluconazole (MIC ≥ 64 μg/ml), 43.3% were resistant to itraconazole (MIC ≥ 1 μg/ml), and 12.5% displayed resistance to amphotericin B (MIC ≥ 2 μg/ml). Newer triazoles, namely, voriconazole, posaconazole, and ravuconazole, had a notable in vitro activity against all Candida species tested. Also, caspofungin was active against Candida sp. isolates (MIC ₉₀ ≤ 0.5 μg/ml) except C . parapsilosis (MIC ₉₀ = 2 μg/ml). It is imperative to promote a national-level surveillance program to monitor this important microorganism.

The in vitro activities of three new triazoles were determined and compared to those of itraconazole and fluconazole against 306 clinical isolates of Blastomycesdermatitidis, Cladophialophora carrionii, Coccidioides immitis, Fonsecaea pedrosoi, Fusarium spp., Histoplasma capsulatum, Paecilomyces lilacinus, Pseudallescheria boydii and Sporothrix schenckii. Minimum inhibitory concentrations (MIC) were determined by a broth macrodilution method of the National Committee for Clinical Laboratory Standards M38-A procedure. Itraconazole (geometric mean MIC, 0.16–0.65 µg/ml), voriconazole (geometric mean MIC, 0.18–1.44 µg/ml), ravuconazole (geometric mean MIC, 0.18–1.09 µg/ml), and posaconazole (geometric mean MIC, 0.18–1.38 µg/ml), had relatively uniform values showing potent in vitro inhibitory activity against B. dermatitidis, C. carrionii, C. immitis, F. pedrosoi, H. capsulatum, and S. schenckii. The in vitro activity was variable with strains of P. boydii,P. lilacinus and Fusarium spp.

The in vitro activity of isavuconazole was compared to those of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and ravuconazole against 300 clinical isolates of Pseudallescheria boydii, Paecilomyces lilacinus, Fusarium spp., Bipolaris spicifera, Curvularia lunata, Alternaria alternata, Exophiala spp., Rhizopus arrhizus, Mucor circillenoides, Absidia corymbifera, Blastomyces dermatitidis, Histoplasma capsulatum and Coccidioides posadasii. MICs were determined by a broth macrodilution method based on the CLSI M38-A procedure. The triazoles were relatively uniform in that they showed strong in vitro inhibitory activity against most of the tested fungi. In vitro activity was variable with strains of P. lilacinus while with Fusarium spp., the triazoles were found to have limited in vitro activity and amphotericin B was moderately active. The results suggest that isavuconazole is a broad-spectrum antifungal agent, effective against a wide range of moulds in vitro.

Posaconazole (SCH 56592) was tested against 25 strains of Coccidioides immitis to determine their in vitro susceptibilities. The geometric mean 48-h MIC of posaconazole (POSA) was 0.5 μg/ml, the MIC range was 0.25 to 1 μg/ml, and the MIC at which 50% of the isolates tested are inhibited (MIC ₅₀ ) and the MIC ₉₀ were 0.5 and 1 μg/ml, respectively. The geometric mean 48-h MIC of itraconazole (ITRA) was 0.23 μg/ml, the MIC range was 0.125 to 0.5 μg/ml, and the MIC ₅₀ and MIC ₉₀ were both 0.25 μg/ml. Two strains of C. immitis were selected for in vivo studies on the basis of the POSA 48-h MICs for the isolates. POSA orally administered at 0.01, 0.1, 0.5, 1, 5, and 10 mg/kg of body weight/day was compared with ITRA administered at 10 and 30 mg/kg three times a day. The spleens and livers of mice that died or survived to day 50 were removed to measure the fungal burdens. Mice had ≥90% survival when they were treated with ≥0.5 mg of POSA per kg or 30 mg of ITRA per kg. Cultures of whole spleens and livers from mice treated with 10 mg of POSA per kg showed ≥70% sterilization. No sterilization of whole spleens and livers from mice treated with ITRA was seen. POSA displayed potent in vivo activity against the two strains of C. immitis tested.

Cryptococcus neoformans infection is an important cause of meningitis in HIV/AIDS endemic regions. Antifungals for its management include amphotericin B, flucytosine, and fluconazole. Recently, treatment of this mycosis with sertraline has been studied with variable clinical outcomes. The aim of the study was to assess the in vitro antifungal effect of sertraline against clinical isolates of Cryptococcus spp. as well as its in vivo activity in a murine model of cryptococcal meningoencephalitis. The in vitro susceptibility to fluconazole, amphotericin B, voriconazole and sertraline of 153 Cryptococcus spp. strains were evaluated according to CLSI procedures. Fungal tissue burden, serum antigenaemia and histopathology, together with the therapeutic efficacy of amphotericin B (3 mg/kg), fluconazole (15 mg/kg), and sertraline (3, 10, and 15 mg/kg) were evaluated in mice intracranially inoculated with one isolate of Cryptococcus neoformans. All strains were susceptible to the antifungals studied and exhibited growth inhibition with sertraline at clinically relevant concentrations. Sertraline at a dose of 15 mg/kg reduced the fungal burden in the brain and spleen with an efficacy comparable to that of fluconazole. In conclusion, sertraline exhibited an excellent in vitro-in vivo anti-cryptococcal activity, representing a possible new alternative for the clinical management of meningeal cryptococcosis.

Thirty isolates of Pseudallescheria boydii were tested to compare the in vitro activity of posaconazole with those of fluconazole and itraconazole, using NCCLS methods. Posaconazole was evaluated in an immunosuppressed mouse model of disseminated pseudallescheriasis. Posaconazole was more effective than itraconazole and as effective as fluconazole in preventing death and significantly reducing the CFU of P. boydii from tissues.