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At least 19 recordsLinked to original sources
PubMed2006

Antifungal effect of voriconazole on intracellular Candida glabrata, Candida krusei and Candida parapsilosis in human monocyte-derived macrophages.

Infections caused by Candida species other than Candida albicans are increasingly common, and decreased susceptibility to azoles has made them more difficult to treat. Since phagocytic killing is important in elimination of Candida infections, intracellular killing of fluconazole-resistant Candida glabrata, Candida krusei and Candida parapsilosis (four strains each) by voriconazole was investigated in human monocyte-derived macrophages (MDMs). MDMs were infected with Candida, and voriconazole was then added. MDMs were lysed at 0, 24 or 48 h after infection, and viable Candida in the lysates enumerated. Compared to the starting inoculum, the number of viable intracellular C. parapsilosis and C. glabrata in untreated MDMs increased to 28,121 and 351 %, respectively, in 48 h. In contrast, the number of C. krusei decreased to 42 %. In MDMs treated with voriconazole, the decrease in viable count was dependent upon drug concentration. At 48 h, C. glabrata was killed only at 5x MIC (P < 0.05), C. krusei was killed at all voriconazole concentrations, while C. parapsilosis was inhibited at 0.5 and 1x MIC and killed at > or = 2.5x MIC (P < 0.05). The data show that intracellular growth and survival of these Candida species in the absence or presence of voriconazole vary markedly. The activity of voriconazole depends on the concentration of the drug and the time of exposure. For the 12 Candida strains studied, regression curves show that the maximum intracellular anticandidal activity of voriconazole was reached at 3.5-5x MIC.

Antifungal Agents↗
PubMedDate not supplied

Candida glabrata, Candida krusei, non-albicans Candida spp., and other fungal organisms in a sixty-bed national cancer center in 1989-1993: no association with the use of fluconazole.

During the 5-year period 1989-1993, the incidence of Candida krusei, and other non-albicans Candida spp., was analyzed in a 60-bed cancer department. The frequency of C. krusei, before fluconazole was introduced into therapeutic protocols in 1990, was 16.5%, and after introduction of fluconazole into prophylaxis in acute leukemia in 1991, the incidence of C. krusei was 12.7%. After 3 years of using this drug in therapy and prophylaxis, the incidence of C. krusei in 1993 was 14.8%, what was lower than before this drug was introduced in our country. 97.6% of all isolated fungi were yeasts and only 2.4% were molds. Among yeasts, the most frequently isolated pathogen was Candida albicans with 64.3% in 1989 and 74.2% in 1993. The next was C. krusei with 21.2% in 1992 and 16.5% in 1989, but 14.8% in 1993, and Candida tropicalis and Candida glabrata with 9.03% in 1989 and 2.7% in 1993. Among the molds, Aspergillus spp. was the most frequently isolated genus. Analyzing the etiology of mycologically proven fungal infections confirmed by positive blood cultures or biopsies, C. albicans and Aspergillus spp. were the most common causative organisms.

Cancer Care Facilities↗
PubMed2003

Three mating type-like loci in Candida glabrata.

Candida glabrata, the second most prevalent Candida species colonizing humans, possesses three mating type-like (MTL) loci (MTL1, MTL2, and MTL3). These loci contain pairs of MTL genes with their respective coding regions on complementary Crick and Watson DNA strands. Each pair of genes is separated by a shared intergenic promoter region, the same configuration found at the mating type loci of Saccharomyces cerevisiae. Two of the MTL loci, MTL1 and MTL2, contain either the MTLa1/MTLa2 configuration or the MTLalpha1/MTLalpha2 configuration in different strains. All but one of the 38 tested C. glabrata strains were either aaalpha or aalphaalpha. One test strain was alphaalphaalpha. Based on the mating type genotype, the MTL genes at the MTL1 or MTL2 loci, and the size of the XbaI fragment harboring MTL1 or MTL2, four classes of C. glabrata strains (I, II, III, and IV) were distinguished. Northern analysis revealed that strains were either a-expressors or alpha-expressors and that expression always reflected the genotype of either the MTL1 or MTL2 locus, depending on the class. The expression pattern in each class, therefore, is similar to that observed in S. cerevisiae, which harbors two silent cassette loci, HMR and HML, and the expression locus MAT. High-frequency phenotypic switching between core phenotypes in an alpha-expressing, but not in an a-expressing, strain modulated the level of MTL expression, suggesting a possible relationship between core phenotypic switching and mating.

Amino Acid Sequence↗
PubMed2002

Phenotypic switching and filamentation in Candida glabrata.

Candida glabrata switches spontaneously, reversibly and at high frequency among the following four phenotypes distinguishable by graded colony colouration on CuSO(4)-containing agar: white (Wh), light brown (LB), dark brown (DB) and very dark brown (vDB). These phenotypes also differ in a graded fashion in the level of expression of the metallothionein gene MTII (Wh vDB), the frequency of switching (Wh>LB>DB>vDB) and colouration on phloxine B-containing agar (Wh>LB>DB>vDB). Switching among the four graded phenotypes is referred to as 'the core switching system'. An additional switch phenotype, 'irregular wrinkle' (IWr), has been identified, which exhibits a highly wrinkled colony morphology. The characteristics of IWr suggest that switching to and from this phenotype represents a second high-frequency switching system. A microscopic analysis revealed that during the first 3 days of colony development, cells in the centres of Wh, LB, DB and vDB colonies expressed almost exclusively the budding yeast phenotype. After 3 days, however, pseudohyphae and cells extending tubes accumulated, so that by 7 days the proportions of these two cellular phenotypes reached 40-50% and 10-20%, respectively. In contrast, IWr colonies were composed almost exclusively of pseudohyphae through the first 6 days of colony development. After 6 days, IWr colonies began to accumulate both budding yeast cells and tubes. The tubes formed by C. glabrata reached lengths of up to six cell diameters, but the tubes did not represent traditional compartmentalized hyphae. Tube growth ended when the tube tip expanded to form a bud. Tubes then functioned as corridors for daughter nucleus migration to the apical bud, and were ultimately left uncompartmentalized and nucleus free. Core switching, pseudohypha formation and tube formation occurred in a majority of 62 tested clinical isolates, demonstrating that these developmental programmes are general characteristics of most strains of C. glabrata.

Blotting, Northern↗
PubMed2006

Kre29p is a novel nuclear protein involved in DNA repair and mitotic fidelity in Candida glabrata.

Candida glabrata KRE29 is an ortholog of Saccharomyces cerevisiae KRE29. S. cerevisiae Kre29p has been identified by affinity purification as a subunit of the Smc5-Smc6 complex, which is required for DNA repair and chromosome segregation. However, mutant phenotypes of S. cerevisiae KRE29 have not been well characterized and none of its orthologs' functions has been reported. Here we report phenotypic characteristics of a C. glabrata kre29 deletant. The absence of C. glabrata Kre29p resulted in decreased viability, exhibiting cell cycle arrest between late S-phase and metaphase even under normal growth conditions, and also caused an increase of plasmid loss rate, implying that Kre29p is required for mitotic chromosome transmission fidelity. The deletant showed increased sensitivity to high temperature as well as to DNA damaging agents including UV, gamma ray, 4-nitroquinoline-1-oxide and methyl methanesulfonate, and the phenotypes were restored in the KRE29 reintegrant. Consistent with the Deltakre29 phenotypes, a Kre29p-GFP fusion protein was located in the nucleus. Furthermore, Kre29p-GFP became concentrated and formed distinct foci after exposure to 4-nitroquinoline-1-oxide. These results suggest the involvement of C. glabrata Kre29p in DNA repair. To our knowledge, this is the first report addressing a cellular protein involved in DNA repair in C. glabrata.

Alleles↗
PubMed1997

Mixed Candida glabrata and Candida albicans disseminated candidiasis in a heroin addict.

The case of a white-heroin addict who developed disseminated candidiasis following coinfection by Candida glabrata and Candida albicans is reported. Genomic random amplified polymorphic DNA typing suggested that the Candida glabrata blood isolates originated in the oral cavity of the patient. This case strengthens the evidence that Candida species other than Candida albicans can be involved in the pathogenesis of disseminated candidiasis in heroin addicts.

AIDS-Related Opportunistic Infections↗
PubMed2006

Clinical significance of azole antifungal drug cross-resistance in Candida glabrata.

Candida glabrata, which can become resistant to fluconazole, is a common cause of bloodstream infection. This study was performed to determine the significance of cross-resistance to new azole drugs among C. glabrata isolates recovered as a cause of infection in azole-treated hematopoietic stem cell transplant (HSCT) recipients. Seven cases of invasive candidiasis caused by C. glabrata occurred in HSCT recipients who were receiving azole therapy between January 2000 and December 2004 in our institution. Case characteristics were ascertained. Sequential colonizing and invasive isolates were examined to determine susceptibilities to fluconazole, itraconazole, and voriconazole, and molecular relatedness by restriction fragment length polymorphism (RFLP) analysis. Twenty-three C. glabrata isolates were recovered from 4 patients who developed candidemia while receiving fluconazole and three patients who developed candidemia while receiving voriconazole. The mode MICs of fluconazole, itraconazole, and voriconazole for these isolates were > or =64 microg/ml (range, 4 to > or =64 microg/ml), 2 microg/ml (range, 0.25 to > or =16 microg/ml), and 1 microg/ml (range, 0.03 to > or =16 microg/ml), respectively. Kendall tau b correlation coefficients demonstrated significant associations between the MICs of voriconazole with fluconazole (P = 0.005) and itraconazole (P = 0.008). Colonizing and invasive isolates exhibiting variable susceptibilities had similar RFLP patterns. These observations suggest that C. glabrata exhibits considerable clinically significant cross-resistance between older azole drugs (fluconazole and itraconazole) and voriconazole. Caution is advised when considering voriconazole therapy for C. glabrata candidemia that occurs in patients with extensive prior azole drug exposure.

Adult↗
PubMed2005

Microsatellite marker analysis as a typing system for Candida glabrata.

Candida glabrata is one of the most important causes of nosocomial fungal infection. We investigated, using a multiplex PCR, three polymorphic microsatellite markers, RPM2, MTI, and ERG3, in order to obtain a rapid genotyping method for C. glabrata. One set of primers was designed for each locus, and one primer of each set was dye labeled to read PCR signals using an automatic sequencer. Eight reference strains including other Candida species and 138 independent C. glabrata clinical isolates were tested. The clinical isolates were collected from different anatomical sites of adult patients either hospitalized in different wards of two different hospitals or not hospitalized. Since C. glabrata is haploid, one single PCR product for each PCR set was obtained and assigned to an allele. The numbers of different alleles were 5, 7, and 15 for the RPM2, MTI, and ERG3 loci, respectively. The number of allelic associations was 21, leading to a discriminatory power of 0.84. The markers were stable after 25 subcultures, and the amplifications were specific for C. glabrata. A factorial correspondence analysis did not indicate any correlation between the 21 multilocus genotypes and the clinical data (source, sex, ward, anatomical sites). Microsatellite marker analysis is a rapid and reliable technique to investigate clinical issues concerning C. glabrata. However, its discriminatory power should be improved by testing other polymorphic microsatellite loci.

Adult↗
PubMed2004

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. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to < or = 1.0 microg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was > or = 2.0 microg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.

Amphotericin B↗
PubMed2004

Systematic identification in silico of covalently bound cell wall proteins and analysis of protein-polysaccharide linkages of the human pathogen Candida glabrata.

Candida glabrata is an important cause of systemic candidiasis in humans. This paper reports a systematic analysis of the putative glycosylphosphatidylinositol-modified (GPI) proteins of C. glabrata, a large part of which are covalently bound to the cell wall glucan network and the remainder of which are retained in the plasma membrane, and of cell wall proteins (CWPs) which are covalently bound in a mild-alkali-sensitive manner. In silico genomic analysis revealed 106 putative GPI proteins. Fifty-one of these GPI proteins could be categorized as adhesive proteins, potentially implicated in fungus-host interactions or biofilm formation during the development of fungal infections. Eleven proteins belonged to well-known GPI protein families of glycoside hydrolases, probably involved in cell wall expansion and remodelling during growth. Other identified GPI proteins included phospholipases, aspartic proteases, homologues of ScEcm33p and ScKre1p, and structural CWPs. Interestingly, the GPI algorithm predicted three orthologues of an abundant CWP in S. cerevisiae, Cwp1p, which is absent in Candida albicans. To evaluate the in silico predictions, isolated cell walls were extracted using HF-pyridine, which specifically cleaves phosphodiester bonds, to release GPI-CWPs. Immunological analysis of the extract using one-dimensional SDS-PAGE and anti-ScCwp1p antiserum indicated the presence of a Cwp1p homologue in C. glabrata cell walls. Further analysis by two-dimensional gel electrophoresis and electrospray ionization tandem mass spectrometry (ESI-MS/MS) confirmed the presence of two of the predicted Cwp1p proteins, Cwp1.1p and Cwp1.2p. Crh1p, a putative 1,3-beta-glucan remodelling enzyme, was also identified. In silico genomic analysis further revealed five putative Pir proteins (Pir1-5p) and five members of the Bgl2 glycoside hydrolase family 17, belonging to a class of putative CWPs that can be extracted with NaOH. Immunological analysis of mild-alkali-extracted CWPs showed the presence of a ScPir2p homologue. Together, these experimental data and in silico predictions represent the first systematic analysis of the C. glabrata cell wall proteome.

Amino Acid Sequence↗
PubMed1992

Disruption analysis of metallothionein-encoding genes in Candida glabrata.

Candida glabrata harbors multiple genes encoding metallothionein (MT). We have disrupted MT-IIa, an amplified locus, and MT-IIb, a single-copy gene, to determine the roles of various MT genes in CuSO4 resistance in C. glabrata. The concentration of CuSO4 required to inhibit the growth by 50% (IC50) of a C. glabrata strain harboring an amplified MT-IIa locus and a single-copy MT-IIb and MT-I genes was 7 mM in a synthetic complete medium. The IC50 decreased to approx. 1 mM when the amplified MT-IIa locus was deleted. The disruption of the MT-IIb gene decreased the IC50 further to 0.1 mM. The CuSO4 resistance in a strain lacking both of the MT-II genes was attributable to MT-I; no evidence was found for the production of (gamma EC)nG isopeptides. The comparison of the nucleotide sequence of MT-IIb to that of MT-IIa revealed the same coding sequence with differences in the 5' region. However, substantial differences were found in the 3' region. MT-IIb was expressed since we were able to purify the protein from the strain that had an intact MT-IIb gene, but a deleted MT-IIa gene. In addition, CuSO4 resistance was provided by MT-IIb. Northern analysis of the total RNA from varied C. glabrata strains indicated no significant changes in the expression of MT-I in the presence or absence of the MT-II genes.

Amino Acid Sequence↗
PubMed2001

Role of ATP-binding-cassette transporter genes in high-frequency acquisition of resistance to azole antifungals in Candida glabrata.

Candida glabrata has been often isolated from AIDS patients with oropharyngeal candidiasis treated with azole antifungal agents, especially fluconazole. We recently showed that the ATP-binding-cassette (ABC) transporter gene CgCDR1 was upregulated in C. glabrata clinical isolates resistant to azole antifungal agents (D. Sanglard, F. Ischer, D. Calabrese, P. A. Majcherczyk, and J. Bille, Antimicrob. Agents Chemother. 43:2753-2765, 1999). Deletion of CgCDR1 in C. glabrata rendered the null mutant hypersusceptible to azole derivatives and showed the importance of this gene in mediating azole resistance. We observed that wild-type C. glabrata exposed to fluconazole in a medium containing the drug at 50 microg/ml developed resistance to this agent and other azoles at a surprisingly high frequency (2 x 10(-4) to 4 x 10(-4)). We show here that this high-frequency azole resistance (HFAR) acquired in vitro was due, at least in part, to the upregulation of CgCDR1. The CgCDR1 deletion mutant DSY1041 could still develop HFAR but in a medium containing fluconazole at 5 microg/ml. In the HFAR strain derived from DSY1041, a distinct ABC transporter gene similar to CgCDR1, called CgCDR2, was upregulated. This gene was slightly expressed in clinical isolates but was upregulated in strains with the HFAR phenotype. Deletion of both CgCDR1 and CgCDR2 suppressed the development of HFAR in a medium containing fluconazole at 5 microg/ml, showing that both genes are important mediators of resistance to azole derivatives in C. glabrata. We also show here that the HFAR phenomenon was linked to the loss of mitochondria in C. glabrata. Mitochondrial loss could be obtained by treatment with ethidium bromide and resulted in acquisition of resistance to azole derivatives without previous exposure to these agents. Azole resistance obtained in vitro by HFAR or by agents stimulating mitochondrial loss was at least linked to the upregulation of both CgCDR1 and CgCDR2.

ATP-Binding Cassette Transporters↗
PubMed1995

Analysis of copper-induced metallothionein expression using autonomously replicating plasmids in Candida glabrata.

Candida glabrata strains and a stable plasmid were developed that were suitable for analysis of copper-inducible expression from promoters of the three metallothionein (MT) genes. The two homologous MTII genes, MTIIa and MTIIb, encode the same polypeptide but are differentially induced by copper salts. MTIIb is more highly inducible than MTIIa and cells harboring a single MTIIb exhibit a greater resistance to copper salts compared to cells harboring a single MTIIa. The differential copper inducibility was mapped to sequences between -03 and -292 upstream of the MT coding sequences. Expression of MTI is highly Cu-regulated, but this MT gene confers much less resistance than MTII genes.

Base Sequence↗
PubMed2000

Management of Infections Caused by Candida glabrata.

Candida glabrata infections undoubtedly have become more frequent, and are now common. They appear to be the consequence of widespread and often indiscriminate use of azoles, especially fluconazole. This species constitutes the Achilles heel of all available azoles, including newer ones in the pipeline. Even when amphotericin B is used, higher dosages are now required. Little is known about the epidemiology of and risk factors for this troublesome species; even less about its virulence factors. However, studying the resistance mechanisms of this haploid organism may provide answers in developing new fungicidal agents.

Journal Article↗
PubMed2005

Effects of voriconazole, granulocyte-macrophage colony-stimulating factor, and interferon gamma on intracellular fluconazole-resistant Candida glabrata and Candida krusei in human monocyte-derived macrophages.

Infections caused by fluconazole-resistant Candida glabrata and Candida krusei are increasingly common causes of morbidity and mortality. We investigated the intracellular killing of fluconazole-resistant C. glabrata and C. krusei by cytokine-activated human monocyte-derived macrophages (MDM) in the presence and absence of voriconazole. For C. glabrata, MDM were activated with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon gamma (IFN-gamma) before infection, after infection, or both before and after infection, whereas for C. krusei MDM were activated with cytokines both before and after infection. Activated MDM were infected, treated with voriconazole, and then lysed, and viable yeast in the lysates enumerated at 0, 24, or 48 h after infection. In the presence of voriconazole (2.5 x MIC), the best activity against C. glabrata occurred when MDM were activated with GM-CSF for 24 h before infection as well as after infection or when they were activated for 24 h before infection alone. A lesser effect was observed when MDM were activated for at least 1 h before infection or when they were treated with cytokines only after infection. IFN-gamma activation had a significant but lesser effect than GM-CSF. Activity against C. krusei in the presence of voriconazole was greatest when MDM were activated with IFN-gamma rather than GM-CSF. Our results suggest that cytokines increase the intracellular anticandidal effect of voriconazole and may be useful as therapeutic adjuvants to voriconazole for treatment of infections caused by fluconazole-resistant C. glabrata and C. krusei.

Antifungal Agents↗
PubMed2005

Prior antimicrobial therapy and risk for hospital-acquired Candida glabrata and Candida krusei fungemia: a case-case-control study.

The incidence of infections caused by Candida glabrata and Candida krusei, which are generally more resistant to fluconazole than Candida albicans, is increasing in hospitalized patients. However, the extent to which prior exposure to specific antimicrobial agents increases the risk of subsequent C. glabrata or C. krusei candidemia has not been closely studied. A retrospective case-case-control study was performed at a university hospital. From 1998 to 2003, 60 patients were identified with hospital-acquired non-C. albicans candidemia (C. glabrata or C. krusei; case group 1). For comparison, 68 patients with C. albicans candidemia (case group 2) and a common control group of 121 patients without candidemia were studied. Models were adjusted for demographic and clinical risk factors, and the risk for candidemia associated with exposure to specific antimicrobial agents was assessed. After adjusting for both nonantimicrobial risk factors and receipt of other antimicrobial agents, piperacillin-tazobactam (odds ratio [OR], 4.15; 95% confidence interval [CI], 1.04 to 16.50) and vancomycin (OR, 6.48; CI, 2.20 to 19.13) were significant risk factors for C. glabrata or C. krusei candidemia. For C. albicans candidemia, no specific antibiotics remained a significant risk after adjusted analysis. Prior fluconazole use was not significantly associated with either C. albicans or non-C. albicans (C. glabrata or C. krusei) candidemia. In this single-center study, exposure to antibacterial agents, specifically vancomycin or piperacillin-tazobactam, but not fluconazole, was associated with subsequent hospital-acquired C. glabrata or C. krusei candidemia. Further studies are needed to prospectively analyze specific antimicrobial risks for nosocomial candidemia across multiple hospital centers.

Anti-Infective Agents↗
PubMed1990

Uptake of pyrimidines and their derivatives into Candida glabrata and Candida albicans.

The uptake of pyrimidines and their derivatives into Candida glabrata and Candida albicans was measured using a novel technique in which the cells were rapidly separated from their suspending medium by centrifugation through a layer of an inert oil. The uptake of [14C]cytosine was linear for 30 s for all concentrations of pyrimidine tested. In C. glabrata but not C. albicans cytosine transport was mediated by both a high affinity (Km 0.8 +/- 0.1 microM), low capacity [V 40 +/- 4 pmol (microliters cell water)-1 s-1] and a low affinity [Km 240 +/- 35 microM], high capacity system [V 770 +/- 170 pmol (microliters cell water)-1 s-1]. The cytosine permease in C. glabrata was specific for cytosine and 5-fluorocytosine. In C. albicans there was only one cytosine transport system [Km 2.4 +/- 0.3 microM; V 50 +/- 4 pmol (microliters cell water)-1 s-1]; this system also transported adenine, guanine and hypoxanthine. Differences in nucleoside transport were also observed for C. glabrata and C. albicans, with the uridine permease in C. glabrata transporting only uridine and 5-fluorouridine whereas cytidine and adenosine were also transported by the uridine permease in C. albicans. Studies on the effect of nucleoside analogues on uridine transport in C. glabrata demonstrated the importance of the sugar moiety in determining the specificity of transport, with a hydroxyl residue on C-2 being apparently essential for transport.

Biological Transport↗
PubMed2004

In vitro activity of voriconazole and other antifungal agents against clinical isolates of Candida glabrata and Candida krusei.

The antifungal susceptibility of 309 Candida glabrata and 63 Candida krusei clinical isolates was tested via the Sensititre YeastOne-3 system (Trek Diagnostic Systems, East Grinstead, UK) to compare the in vitro activity of voriconazole with that of five other antifungal agents (amphotericin B, fluconazole, itraconazole, ketoconazole, and flucytosine). Voriconazole was highly active (MIC90, 0.5 microg/ml) against isolates of both species, including those for which the MICs of itraconazole and fluconazole were high (MIC90s of itraconazole, 2 microg/ml for C. glabrata and 0.5 microg/ml for C. krusei; MIC90s of fluconazole, 32 microg/ml for C. glabrata and 64 microg/ml for C. krusei). Ketoconazole MIC90 values for both species were identical to those of voriconazole. The MIC90 of amphotericin B was similar for both species (0.125 microg/ml for C. glabrata and 0.25 microg/ml for C. krusei). As expected, flucytosine was only moderately active against C. krusei isolates (MIC90, 16 microg/ml) but was highly active against C. glabrata isolates (MIC90, 0.03 microg/ml). Potential cross-resistance within the azole class was noted for some strains of C. glabrata (5.5%) that presented high MIC values for all the azoles tested. In order to consider voriconazole a viable alternative to other triazoles for the treatment of infections caused by Candida species, susceptibility testing of all clinically significant isolates of C. glabrata and C. krusei is recommended because of the potential for azole cross-resistance. The Sensititre YeastOne-3 seems to be a suitable commercial tool for this purpose.

Antifungal Agents↗