Effects of amphotericin B on Aspergillus flavus clinical isolates with variable susceptibilities to the polyene in an experimental model of systemic aspergillosis.

Objectives: The aim of the present study was to evaluate the effects of amphotericin B (AMB) on clinical isolates of Aspergillus flavus.

Methods: MICs of both standard AMB and liposomal AMB (L-AMB) were determined using a broth dilution method for seven isolates of A. flavus.

In vitro and in vivo effects of echinocandins against Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis.

Objectives: The aim of the present study was to compare, in vitro and in vivo, the effects of caspofungin, micafungin and anidulafungin against Candida parapsilosis complex isolates.

Methods: In vitro activities of all three echinocandins were assessed against C. parapsilosis sensu stricto (n = 4), Candida orthopsilosis (n = 4) and Candida metapsilosis (n = 3) using broth microdilution susceptibility testing, minimum fungicidal concentration determination and a killing-curve assay, in the absence and in the presence of 50% human serum.

Comparative effects of micafungin, caspofungin, and anidulafungin against a difficult-to-treat fungal opportunistic pathogen, Candida glabrata.

The aim of this study was to compare the in vitro and in vivo activities of micafungin, caspofungin, and anidulafungin against Candida glabrata. The MICs against 28 clinical isolates showed that the overall susceptibilities to caspofungin and to micafungin were not statistically different in the absence of human serum, whereas the isolates were less susceptible to micafungin than to caspofungin in its presence. Minimum fungicidal concentrations, as well as time-kill experiments, showed that caspofungin was more active than anidulafungin, while micafungin was superior to either caspofungin or anidulafungin without serum; its addition rendered caspofungin and micafungin equally effective.

Heterozygosis and pathogenicity of Cryptococcus neoformans AD-hybrid isolates.

Nineteen Cryptococcus neoformans AD-hybrid isolates were investigated to assess whether hybrid genomic background could affect virulence in a mouse model. The level of heterozygosity of each strain was analyzed using primers specific for allele A and D of 15 polymorphic genes. Virulence was tested in a mouse model of systemic infection by measuring time of survival.

In vitro and in vivo activities of posaconazole against zygomycetes with various degrees of susceptibility.

Objectives: We analysed the in vitro and in vivo effects of posaconazole and amphotericin B against three clinical isolates of zygomycetes: Lichtheimia corymbifera, F1; and Rhizopus oryzae, F5 and F6.

Methods: In vitro activities of both drugs were assessed by determining MICs, minimum fungicidal concentrations (MFCs) and fungal damage measured by the XTT assay against either the spores or the hyphal forms. Additionally, the survival curves of neutropenic mice systemically infected with the zygomycete isolates were used as the marker of antifungal response to amphotericin B (1 mg/kg/day) or posaconazole (2.

Disruption of homocitrate synthase genes in Candida albicans affects growth but not virulence.

Two genes, LYS21 and LYS22, encoding isoforms of homocitrate synthase, an enzyme catalysing the first committed step in the lysine biosynthetic pathway, were disrupted in Candida albicans using the SAT1 flipper strategy. The double null lys21Δ/lys22Δ mutant lacked homocitrate synthase activity and exhibited lysine auxotrophy in minimal media that could be fully rescued by the addition of 0.5-0.

Anidulafungin in combination with amphotericin B against Aspergillus fumigatus.

We investigated the effects of anidulafungin alone and in combination with amphotericin B against Aspergillus fumigatus. Indifference was the only type of interaction observed in vitro. Anidulafungin at 1 and 5 mg/kg of body weight/day, amphotericin B at 1 mg/kg/day, and combination therapy prolonged the survival of mice with invasive aspergillosis.

In vitro susceptibility of dermatophytes to conventional and alternative antifungal agents.

The minimum inhibitory concentrations (MICs), the minimal fungicidal concentrations (MFCs), the fungal biomass (FB) and hyphal viability employing the dye 3-4,5 dimethyl- 2-thiazolyl- 2,5- diphenyl- 2H tetrazolium bromide (MTT) were used to compare the in vitro effects of fluconazole (FLU) with those of the N-terminal palmitoyl-lipidated peptide, Pal-Lys-Lys-NH(2) (PAL), and a tea tree oil component, gamma-Terpinene (TER), against several clinical isolates of Microsporum canis and Trichophyton rubrum. In general, FLU and PAL MICs were significantly lower than those observed with TER, while no differences in the three drugs were found in the MFCs. However, they were from two to 16-times higher than their respective MICs.

Evaluation of the disk diffusion method compared to the microdilution method in susceptibility testing of anidulafungin against filamentous fungi.

Susceptibility testing of anidulafungin (AFG) against 32 mold isolates showed an excellent correlation between disk diffusion (DD) and broth microdilution methods. Based on our data, a 2-microg disk of AFG and a 24-h reading time might represent the best parameters for AFG DD testing against filamentous fungi.

Posaconazole against Candida glabrata isolates with various susceptibilities to fluconazole.

We investigated the in vitro activities of posaconazole (POS), fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS) against four clinical isolates of Candida glabrata with various susceptibilities to FLC (FLC MICs ranging from 1.0 to >64 microg/ml). POS MICs ranged from < or =0.

Posaconazole activity against Candida glabrata after exposure to caspofungin or amphotericin B.

We evaluated the effects of sequential therapy with caspofungin (CAS) or amphotericin B (AMB) followed by posaconazole (POS) against Candida glabrata. The susceptibilities to POS of yeast cells pre-exposed to CAS or AMB were identical to those of untreated cells as shown by standard Clinical and Laboratory Standards Institute broth dilution, cell viability, and disk diffusion methods. We then investigated the activity of sequential regimens in an experimental model of disseminated candidiasis.

Comparison between disk diffusion and microdilution methods for determining susceptibility of clinical fungal isolates to caspofungin.

We compared the caspofungin (CAS) susceptibility testing results generated by the disk diffusion (DD) assay with the results of the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BD) reference method for 106 yeast isolates. The isolates represented 11 different fungal species, including Candida albicans (n = 50), C. parapsilosis (n = 10), C.

Fluconazole susceptibility of Candida spp. isolates collected over nine years in a teaching hospital of Ancona, Italy.

The in vitro activity of fluconazole was investigated against 476 yeast isolates collected during a 9-year period (1997-2005) from patients hospitalised in a teaching hospital of Ancona. They included 373 isolates of Candida albicans, 53 of Candida glabrata and 50 of Candida parapsilosis. Minimum inhibitory concentrations (MICs) determined in accordance with the Clinical Laboratory Standards Institute methodology showed that 96% of the isolates were susceptible (MIC < or =8.

Caspofungin in combination with amphotericin B against Candida parapsilosis.

Candida parapsilosis has emerged as an important nosocomial pathogen. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of caspofungin (CAS) in combination with amphotericin B (AMB) against three clinical isolates of C. parapsilosis.

Posaconazole prophylaxis in experimental systemic zygomycosis.

Three isolates of zygomycetes belonging to two different genera (Rhizopus oryzae and Absidia corymbifera) were used to produce a systemic infection in neutropenic mice. On days -2 and -1 and at 2 h prior to infection, the mice received either posaconazole (POS) at doses ranging from 20 to 80 mg/kg of body weight/day or amphotericin B (AMB) at 1 mg/kg/day. Antifungal drug efficacy was assessed by determination of the prolongation of survival, determination of the percentage of infected organs (brain, lung, spleen, and kidney), and histological examination for the number of infection foci and their sizes in brain and kidney tissues.

Effects of caspofungin against Candida guilliermondii and Candida parapsilosis.

The in vitro activity of caspofungin (CAS) was investigated against 28 yeast isolates belonging to Candida albicans (n = 5), Candida guilliermondii (n = 10), and Candida parapsilosis (n = 13). CAS MICs obtained by broth dilution and Etest methods clearly showed a rank order of susceptibility to the echinocandin compound with C. albicans > C.

Candida guilliermondii fungemia in patients with hematologic malignancies.

The microbiological, clinical, and epidemiological features of most non-Candida albicans Candida species are well known, but much less is known about species such as Candida guilliermondii, an uncommon pathogen causing a variety of deep-seated infections in immunocompromised hosts. To characterize C. guilliermondii fungemia in patients with hematological malignancies and its susceptibility to antifungal drugs, all cases of C.

Efficacy of caspofungin against Aspergillus terreus.

We investigated the in vitro and in vivo activities of caspofungin against Aspergillus terreus. The drug increased survival and reduced tissue fungal burden in neutropenic mice. Therefore, our data support the role of caspofungin in treating systemic infections due to this emerging pathogen.

Comparison of the fungicidal activities of caspofungin and amphotericin B against Candida glabrata.

We investigated the fungicidal activity of caspofungin (CAS) and amphotericin B (AMB) against 16 clinical isolates of Candida glabrata. The minimum fungicidal concentrations (MFCs) of CAS were similar to those of AMB, ranging from 2.0 to >8.

Comparative analysis of pathogenicity of Cryptococcus neoformans serotypes A, D and AD in murine cryptococcosis.

Objectives: To characterize the pathogenicity of 15 strains of Cryptococcus neoformans belonging to several serotype/mating type allele patterns (Dalpha, Da, A(alpha), A(a), A(alpha)/D(a) and D(alpha)/A(a)) in experimental models of murine cryptococcosis.

Methods: CD1-infected mice were examined for survival and fungal loads in either brain or lung during the course of infection.

Results: All strains, with the exception of one Da strain, produced melanin in vitro.

Caspofungin in combination with amphotericin B against Candida glabrata.

The effects of caspofungin combined with amphotericin B were investigated with Candida glabrata. Although in vitro experiments showed an indifferent interaction, the combination regimen was the only therapeutic approach yielding organ sterilization in a murine candidemia model.

Genotypic variation and antifungal susceptibilities of Candida pelliculosa clinical isolates.

At the Istituto Ricovero Cura Carattere Scientifico, Ospedale Maggiore di Milano, Italy, Candida pelliculosa accounted for 3.3 and 4.4 % of all Candida species other than Candida albicans collected during 1996 and 1998, respectively.

Tolerance to amphotericin B in clinical isolates of Candida tropicalis.

A broth microdilution method was used for testing amphotericin B against 33 clinical isolates of Candida tropicalis. All isolates were in vitro susceptible to the polyene (MIC [minimal inhibitory concentration] < or = 1.0 microg/mL).

Sequential therapy with caspofungin and fluconazole for Candida albicans infection.

A sequential therapy of caspofungin (CAS) and fluconazole (FLC) administration for treatment of Candida albicans infection was investigated. Treatment with CAS followed by FLC was as effective as CAS treatment given alone for the same duration. Our data suggest that switching from CAS to FLC is a potentially explorable therapeutic option for treatment of systemic candidiasis.

In vitro activities of voriconazole in combination with three other antifungal agents against Candida glabrata.

Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata.