In vitro susceptibility of yeasts for fluconazole and itraconazole. Evaluation of a microdilution test

In vitro susceptibilities were determined for a total of 159 clinical isolates and 12 reference strains of yeasts belonging to different Candida species including 94 Candida albicans strains, and further genera such as Cryptococcus, Trichosporon, Geotrichum and Saccharomyces. Minimum inhibitory concentration (MIC) values for fluconazole and itraconazole were assessed using a microdilution technique with the semisynthetic high resolution (HR) medium supplemented with glucose and asparagine but without sodium hydrogen carbonate (pH 7.0), according to a proposal of the working group 'Clinical Mycology' of the German Speaking Mycological Society. Fluconazole MIC values for C. albicans were between 0.125 and > or = 128 micrograms ml-1. Thus, the median of 1 microgram ml-1 showed that the overall fluconazole susceptibility was good. As expected, Candida krusei (seven strains) exhibited diminished in vitro susceptibility with MIC values for fluconazole of 8 to 128 micrograms ml-1 with a median of 64 micrograms ml-1. Some Candida kefyr strains seemed to be less susceptible against fluconazole which was indicated by a MIC90 of 64 micrograms ml-1. Surprisingly, no Candida glabrata isolate exhibited a MIC value greater than 16 micrograms ml-1. Other Candida species, Trichosporon cutaneum, Geotrichum candidum and Saccharomyces cerevisiae showed low MICs to fluconazole. In vitro susceptibility testing of itraconazole revealed that all Candida species except C. albicans, but also Trichosporon cutaneum, Geotrichum candidum, and Saccharomyces cerevisiae exhibited acceptable low MIC values against itraconazole (0.03-2 micrograms ml-1). Their MIC90 values for itraconazole were in the close range between 0.125 and 2 micrograms ml-1. MIC values between 0.125 and 2 micrograms ml-1 were obtained, even for C. krusei strains. On the other hand, the range of C. albicans MICs was between 0.0125 and > or = 16 micrograms ml-1 with MIC50 and MIC90 values of 0.125 and > or = 16 micrograms ml-1, respectively, indicating that a considerable number of yeast strains have high MICs. The comparative evaluation of different experimental conditions revealed that there exists a marked influence both of inoculum size and incubation time on the results of susceptibility testing. Therefore, for routine usage 10(2) CFU ml-1 and 18-24 h incubation time for this microdilution method with HR medium are recommended.     

Antifungal susceptibility testing of Candida albicans by flow cytometry

Antifungal susceptibilities of 28 Candida albicans isolates and two quality control strains to amphotericin B and fluconazole were determined by flow cytometry and microdilution method. Minimum inhibitory concentrations (MICs) obtained by flow cytometry were compared with the results obtained by The National Committee for Clinical Laboratory Standards Subcommittee (NCCLS) broth microdilution method. The agreement of results (within two dilution) obtained was found as 96 and 93% for amphotericin B and fluconazole, respectively. At least 24 h incubation was required for reading the microdilution assays. Four hours of incubation was required for fluconazole, whereas 2-h incubation was sufficient for amphotericin B to provide MIC by flow cytometry. Results of this study show that flow cytometry provides a rapid and sensitive in vitro method for antifungal susceptibility testing of Candida albicans isolates.     

Effect of culture media on in vitro susceptibility testing of fluconazole against some yeasts

Thirty clinical isolates, comprising six strains of Candida albicans, and four strains each of C. lusitaniae, C. parapsilosis, C. tropicalis, Cryptococcus neoformans, Torulopsis glabrata and Trichosporon beigelii were tested against fluconazole, using Sabouraud's dextrose (SD) broth and a high resolution (HR) medium (Pfizer Central Research, Inc.). The procedure was a standard tube (1 ml/tube) dilution, and C. albicans Y01 09 was included as a reference strain to monitor quality and reproducibility. Results indicated that the minimum inhibitory concentrations (MICs) for all isolates of C. albicans, C. lusitaniae, C. tropicalis, and Tr. beigelii were 100 micrograms ml-1 or greater in the SD medium. In the HR medium, however, the MICs for two isolates of C. albicans were 1.56 micrograms ml-1, in other four gave higher values (greater than 100 micrograms ml-1), and the results for C. lusitaniae and Tr. beigelii were in the range 1.56-3.12 micrograms ml-1. The MICs for C. tropicalis were unaffected (100 micrograms ml-1) by the medium used. All Cr. neoformans isolates yielded a uniform value (1.56 micrograms ml-1) in HR medium as compared to somewhat more variable results (MICs 0.39-1.56 micrograms ml-1) in SD broth. The MICs for T. glabrata in the SD and HR media were 3.12-12.5 and 6.25 micrograms ml-1, respectively. The data indicated that the HR medium is preferable for the in vitro susceptibility testing of C. albicans, C. lusitaniae and Tr. beigelii to fluconazole. The MICs for other yeasts were not affected by the culture medium. The reference C. albicans isolate yielded an MIC of 1.56 micrograms ml-1 throughout.     

Phenotypic variation and antifungal susceptibility patterns of Candida albicans strains isolated from neutropenic patients

The aim of this study was to investigate the relationship between phenotypes of Candida albicans strains isolated from clinical specimens and the susceptibility of the strains to three antifungal agents, fluconazole, amphotericin B and flucytosine. Oropharyngeal, gastrointestinal and urogenital tract specimens were collected from 122 neutropenic patients who had received no previous prophylactic treatment. Each of 122 C. albicans strains recovered was found to express one of the six phenotypes: smooth, fuzzy, irregular, star, ring and stipple. The mean minimum inhibitory concentrations (MICs) of fluconazole was consistently higher for C. albicans strains expressing the stipple phenotype. The mean MICs for the six phenotypes of C. albicans strains ranged between 1.22 and 7.94 micrograms ml-1 for fluconazole, 0.99 and 2.55 micrograms ml-1 for amphotericin B and 1.23 and 1.83 micrograms ml-1 for flucytosine. The antifungal susceptibility of the stipple phenotype requires attention, especially in patients who are clinically unresponsive to fluconazole chemotherapy or in cases of life-threatening C. albicans infections of immunocompromised hosts. Long-term use of fluconazole may explain the outcome of the resistant stipple phenotype.     

Evaluation of the microdilution, Etest and disk diffusion methods for antifungal susceptibility testing of clinical strains of Trichosporon spp

Trichosporon spp are well recognized as pathogens capable of causing invasive disease. Despite the increasing frequency and severity of trichosporonosis, data on the antifungal susceptibility of Trichosporon spp. are limited and recommendations for in vitro testing of this fungus are not included in the guidelines of the National Committee for Clinical Laboratory Standards. The purpose of this study was to determine the in vitro susceptibility of clinical Trichosporon isolates to systemic antifungals. We evaluated the in vitro activity of amphotericin B, fluconazole, itraconazole and voriconazole against 27 clinical isolates of Trichosporon spp. (14 T. mucoides and 13 T. asahii) using NCCLS M27-A2 reference microdilution, Etest and disk diffusion methods. In the microdilution and Etest methods Trichosporon spp. demonstrated relatively high minimum inhibitory concentrations (MICs) for fluconazole (MIC90 4 and 6 microg/ml, respectively) and relatively low MICs for voriconazole (MIC90 0.125 and 0.125 microg/ml, respectively). MICs for amphotericin B determined on antibiotic medium 3 were lower (MIC90 0.06 microg/ml) than those on RPMI (MIC90 1 microg/ml). Observed agreements were 81-100% according to these drugs. Disk diffusion zone diameters correlate inversely with MICs from dilution tests except for amphotericin B. Validation of the clinical significance of these observations demands determination of MIC breakpoints for Trichosporon and in vitro- in vivo correlation studies.     

Vergleich von drei Antimykotika-Empfindlichkeitsprüfungs-Methoden für die In-vitro-Testung von Candida-Isolaten von Patienten mit HIV-Infektion

Zusammenfassung. Es wurden die MHK-Werte für Fluconazol von 90 Candida -Isolaten (56 C. albicans , 15 C. glabrata , 9 C. krusei und 10 C. tropicalis ) untersucht. Zur Antimykotika-Resistenztestung wurden die Mikrodilutionsmethoden nach dem Protokoll M27-P des NCCLS (M27-Pmicro) mit RPMI 1640-Medium sowie der Methode nach Troke & Pye mit HR-Medium (HRmicro) als auch die Agardiffusionsmethode mit dem Etest (YNB-Agar) verwendet. Die Ergebnisse mit diesen Methoden wurden mit den klinischen Befunden verglichen. Sämtliche C. albicans -Isolate von AIDS-Patienten mit Fluconazol-refraktärer Candidose hatten MHK-Werte entweder ≥ 6,25 μg/ml (M27-Pmicro) oder ≥ 25 μg/ml (HRmicro und Etest). Andererseits lagen die MHK-Werte von C. albicans -Isolaten bei AIDS-Patienten mit Fluconazol-empfindlicher Candidose teil-weise ebenfalls über diesen Endpunkten. Ein mögliches Ansprechen auf eine Fluconazol-Therapie kann somit nicht zwangsläufig von dem MHK-Wert abgeleitet werden.
Summary. The MIC values of fluconazole were determined for 96 Candida isolates (56 C. albicans , 15 C. glabrata , 9 C. krusei and 10 C. tropicalis ). The methods employed for antifungal susceptibility testing were: microdilution according to the protocol M27-P of the NCCLS (M 27-Pmicro) using RPMI 1640 medium or HR medium following Troke & Pye (HRmicro) as well as the agar diffusion method by means of the Etest (YNB agar). The in vitro results were compared with the clinical outcome of patients. All C. albicans isolates received from AIDS patients with fluconazole-refractory candidosis showed MICs of ≥ 6,25 mg/ml (M27-Pmicro) or ≥ 25 mg/ml (MRmicro) and Etest). On the other hand some MICs of C. albicans isolates from AIDS patients with fluconazole-sensitive candidosis were also beyond these breakpoints. Therefore a possible success of a fluconazole therapy cannot unequivocally be predicted from the MIC value determined in vitro.     

In vitro susceptibility of Cryptococcus neoformans clinical isolates from Egypt to seven antifungal drugs

The in vitro susceptibility of 29 clinical isolates of Cryptococcus neoformans to fluconazole, miconazole, itraconazole, ketoconazole, flucytosine, nystatin and amphotericin B was tested by broth and colorimetric microdilution methods. Most of the isolates showed uniform patterns of susceptibility to the used antifungal agents. Only three isolates exhibited resistance [fourfold or greater rise in the minimum inhibitory concentrations (MICs)] to the tested antifungal drugs. The MIC50 and MIC90 were 0.5-8 mg l(-1) for 5-flucytosine, 0.2-8.25 mg l(-1) for nystatin, 0.5-16 mg l(-1) for fluconazole and 0.2-12.5 mg l(-1) for miconazole. However, MIC50 and MIC90 were in narrow range for the clinical yeast isolates in both methods used and showed 0.5-1 mg l(-1) for amphotericin B and 0.016-0.25 mg l(-1) for both ketoconazole and itraconazole. The combination of fluconazole plus flucytosine showed greater synergistic and fungicidal activity compared with that of fluconazole plus amphotericin B or the use of individual drugs.     

Determination of minumum inhibitory concentrations of Candida species isolated from vaginal swab specimens by using broth macrodilution and E-test

The purpose of the present study was to evaluate the utility of the E-test in determining the antifungal susceptibility of Candida species. A total of 50 Candida strains, including 34 Candida albicans and 16 non-albicans were isolated from vaginal swab specimens from women suffering from vaginitis. The minimum inhibitory concentrations (MICs) of amphotericin B, fluconazole and ketoconazole were detected by using broth macrodilution and the E-test. When the results of the two tests were compared, the MIC values were considered acceptable if the difference between the two assays was no more than two-fold (+/-1dilution). The acceptable rates were: 84% for amphotericin B, 97% for fluconazole and 78% for ketoconazole. Finally, MICs of C. albicans against the tested antifungal agents were generally lower than for non-albicans strains. These results suggest that the E-test can be used for the determination of MIC values for Candida species isolates.     

In Vitro Antifungal Activity of Saperconazole (R 66905) Against Candida and Torulopsis Die antimyzetische Aktivität von Saperconazol (R 66905) in vitro gegen Candida und Torulopsis

The susceptibility of several strains of Candida and Torulopsis to saperconazole, a new triazole antifungal compound, was compared to that of ketoconazole. The MICs of the two antifungal agents were determined against 70 strains of Candida albicans, 10 strains of C. guilliermondii, 10 strains of C. krusei, 10 strains of C. parapsilosis, 10 strains of C. pseudotropicalis, 10 strains of C. tropicalis and 15 strains of Torulopsis glabrata. The fungistatic activity was evaluated by the agar dilution method using BHI and casitone media after incubation for 48 hours at 28-30 degrees C. The in vitro activity of saperconazole was similar to that of ketoconazole for most of the Candida spp. tested except for C. krusei in particular. An MIC of less than or equal to 3.12 micrograms/ml for saperconazole was found with 92% of the C. albicans strains tested. In contrast, T. glabrata was more susceptible to ketoconazole.     

Case report. Osteomyelitis caused by high resistant Candida guilliermondii

We describe a case of a 57-year-old patient with osteomyelitis at a finger of his right hand caused by Candida guilliermondii. The strains isolated were highly resistant to fluconazole and itraconazole. Using the three methods, microdilution, agardilation and E-test, the highest minimum inhibitory concentrations (MICs) amounted to > 256 micrograms ml-1 for fluconazole and > 32 micrograms ml-1 for itraconazole. To our knowledge, this is the first time such high values have been described for C. guilliermondii. They correlated with the therapeutic non-response to a triazole therapy in our patient. The patient was cured by partial amputation of the affected finger.     

In vitro activity of nitroxoline against clinical isolates of Candida species

The in vitro antifungal activity of the quinoline nitroxoline has been compared with those of amphotericin B, flucytosine, and two azoles, miconazole and ketoconazole, against clinical isolates of Candida spp. A total of 186 isolates of 10 species of Candida and two culture collection strains were tested by an agar-dilution technique. Nitroxoline was highly active against Candida spp. MICs for nitroxoline ranged between 0.25-2 micrograms ml-1 for 186 representative strains. With MIC90 as the measure of antifungal activity, nitroxoline appeared to be superior to the imidazoles studied. Data for individual species of Candida revealed that the activities of nitroxoline and amphotericin B were generally just as effective against C. albicans, whereas flucytosine was the most active agent against Candida spp.     

Comparison of microdilution and disc diffusion methods in assessing the in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil against vaginal Candida isolates

The in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil was evaluated against 99 vaginal Candida strains by the broth microdilution and disc diffusion methods. The microdilution method was performed in accordance with NCCLS-M27A guidelines. An investigational method was used for the disc diffusion test. Fluconazole and tea tree oil minimum inhibitory concentrations (MICs) obtained at 48 h tended to increase 1- to 2-fold or remain the same compared to 24 h readings for most of the isolates tested. C. krusei and C. norvegensis had significantly higher MICs and smaller inhibition zones for fluconazole compared to other species. Tea tree oil MICs were found to be similar, in general, for all Candida spp. tested. The geometric mean MIC of tea tree oil for all isolates was 2.2% (range, 0.25-4%) at 24 h and 3.0% (range, 1-8%) at 48 h. Tea tree oil mean inhibition zone diameter was 24 mm (range, 14-42 mm) at 24 h and 15.8 mm (range, 10-35 mm) at 48 h. In vitro activity of tea tree oil against fluconazole-resistant Candida strains was of particular interest. The isolates had similar tea tree oil MICs and inhibition zone diameters regardless of their fluconazole susceptibility profile. Tea tree oil MIC ranges (inhibition zone diameter ranges) were 2-4% (12-21 mm) and 2% (35 mm) at 48 h for C. krusei and C. norvegensis, respectively. These results suggest that tea tree oil MICs of the fluconazole-resistant isolates are comparable to those of fluconazole-susceptible isolates. This in vitro finding is promising for potential use of topical tea tree oil formulations in the treatment of candidiasis due to fluconazole-resistant strains.     

Fluconazole susceptibility of Candida isolates from oropharyngeal candidosis

Summary. Fifty strains of Candida isolated from 38 patients with oropharyngeal candidosis were tested in vitro for fluconazole susceptibility with a disk diffusion test and for determination of minimal inhibitory concentrations (MICs). For 25 patients treated with fluconazole, the relationship between in vitro susceptibility and clinical outcome was analysed. A good correlation between in vitro results and therapeutic efficacy was found. In only one case was treatment failure associated with a susceptible strain. Mixed cultures of Candida albicans and non- albicans Candida species were not uncommon and, more interestingly, some samples contained different strains of C. albicans with varied fluconazole susceptibilities. Good agreement was observed between the two techniques used for fluconazole susceptibility testing.
Zusammenfassung. Mittels Diffusionstest und Microdilutionstest wurden Suszeptibilität und minimale Hemmkonzentrationen für Fluconazol an 50 Candida -Stämmen bestimmt, die von 38 Patienten mit oropharyngealer Candidose gewonnen worden waren. Bci 25 Fluconazol-behandelten Patienten wurde das Verhaltnis der Suszeptibilität in vitro mit dem klinischen Therapieergebnis verglichen. Zwischen beiden Parametern wurde eine gute Korrelation gefunden. Nur in einem Fall war ein Therapieversagen mit einem suszeptiblen Stamm assoziiert. Mischkulturen von Candida albicans und nicht- albicans-Candida -Arten waren nicht ungewöhnlich, und—noch interessanter—einige Proben enthielten mehrere Candida albicans -Stämme mit unterschiedlicher Fluconazol-Suszeptibilität. Auch wurde eine gute Überein-stimmung zwischen den beiden Techniken gefunden, die zur Fluconazol-Suszeptibilitäts-bestimmung eingesetzt waren.     

In vitro comparative evaluations of the postantifungal effect: synergistic interaction between flucytosine and fluconazole against Candida albicans

In vitro comparative evaluations were performed to study the efficacy of combinations of flucytosine and fluconazole in producing a postantifungal effect (PAFE) on Candida albicans. Initial studies were done to determine MIC, FIC (fractional inhibitory concentration) and optimal PAFE parameters. A turbidometric method was used to measure yeast cell growth following exposure to different concentrations of the two drugs for periods of 0.5, 1 or 2 h at temperatures of 30 degrees C and 37 degrees C. The PAFE was determined by the difference in time (h) required for growth of the control and test cultures to reach the 0.5 absorbance level following removal of the drug by dilution. Ten strains of C. albicans were then assayed (30 degrees C; 2 h exposure time) and a synergistic PAFE was evidenced with the two drugs at concentrations well below their individual MICs. PAFEs ranging from 3.8 to 10.5 h, which persisted for 1.2-2.5 h longer than those achieved with either agent separately, were evidenced when flucytosine and fluconazole were combined (flucytosine: fluconazole ratios of 1:16-1:32) at concentrations ranging from 0.024 to 0.098 micrograms ml-1 and 0.78 to 1.56 micrograms ml-1 respectively. The concentrations of each agent required to produce an optimal PAFE varied according to the C. albicans strain being assayed.     

Susceptibility to ketoconazole of Candida albicans strains from sequentially followed HIV-1 patients with recurrent oral candidosis

The MIC values of the antifungal drug ketoconazole were evaluated on 66 Candida albicans strains. These strains were isolated from 26 HIV-1 infected patients with oral recurrent candidosis. Each episode of oral candidosis observed in these patients was orally treated with ketoconazole (200 mg/day) until the clinical disappearance of the lesions. The most frequent MIC values were 20 micrograms/ml and 10 micrograms/ml, observed in 37 and 19 isolates respectively. Only strains from five patients showed changes in their susceptibility to ketoconazole. This fact could indicate that a different strain causes the subsequent reappearance of the oral lesions, rather than the drug selecting resistant fungal strains. Our results stress the role of host characteristics in the occurrence of candidal infections, pointing to the progressing failure of the immunological response as the most important factor responsible for the recurrence of oral candidosis during HIV-1 infection.     

In vitro activity of cefpirome (HR 810) against enterococci and staphylococci.

The inhibitory activity of cefpirome (HR 810), a new cephalosporin derivative for parenteral use, was tested by agar dilution methods against Enterococcus faecalis (100 strains), Staphylococcus aureus (40 strains) and coagulase-negative staphylococcal species (60 strains) in comparison with other beta-lactam antibiotics. For E. faecalis, the cefpirome minimum inhibitory concentration (MIC) range was 2-128 micrograms/ml, with an MIC50 of 8 micrograms/ml, and an MIC90 of 64 micrograms/ml. The optimal bactericidal activity against strains with MICs of < or = 8 micrograms/ml occurred at 2-4 times the MIC, and the reduction in the initial inoculum was 99.9-99.7% after 24 h incubation at these concentrations. Mec gene-negative staphylococci (both S. aureus and coagulase-negative species) had cefpirome MICs of 0.25-2 micrograms/ml (MIC50 0.5 microgram/ml, MIC90 1 microgram/ml). Mec gene-positive strains had MICs of 0.5-128 micrograms/ml (MIC50 2 micrograms/ml, MIC90 32 micrograms/ml). Strains with borderline resistance to oxacillin which did not harbor the mec gene and which were susceptible to cefpirome maintained their susceptibility even when high-density inocula were used and after several passages in media containing the antibiotic. These studies present some potential advantages of cefpirome over other cephalosporins in the inhibitory activity against Gram-positive cocci.     

Fluconazole and itraconazole susceptibilities of Candida spp. isolated from oropharyngeal specimens and blood cultures of paediatric haematology/oncology patients

This study examined the in vitro susceptibilities to fluconazole and itraconazole of isolates of Candida spp. from surveillance oropharyngeal specimens and blood cultures from paediatric patients with malignancy. The species distribution of 100 isolates from oropharyngeal specimens was C. albicans 86%, C. glabrata 7%, C. lusitaniae 4%, C. parapsilosis 2% and C. tropicalis 1%. From a total of nine isolates from blood cultures the species distribution was C. albicans 33.3%, C. parapsilosis 33.3 % and C. guilliermondii 33.3%. Only three of the oropharyngeal isolates were resistant to fluconazole (MIC > or = 64 mg l(-1)) and only two were resistant to itraconazole (MIC > or = 1 mg l(-1)). None of the blood culture isolates was resistant to either agent. At this centre, C. albicans is the predominant species from oropharyngeal specimens, but non-albicans Candida species predominate in blood cultures. Although resistance to fluconazole and itraconazole is rare at present, continued surveillance is warranted to monitor trends in species distribution and antifungal susceptibility.     

Direct fluconazole susceptibility testing of positive Candida blood cultures by flow cytometry

The standard methods for yeast susceptibility testing require 24–48 h of incubation. As there has been an increase in incidence of non- albicans Candida species, the clinician is very often wary of initiating therapy with fluconazole until a final susceptibility report is generated, especially when treating very sick patients. A rapid reliable susceptibility testing method would enable the clinician to prescribe fluconazole, thus avoiding more toxic or expensive therapy. To determine the feasibility of direct susceptibility testing of Candida species to fluconazole by a rapid flow cytometric method, 50 Candida strains were seeded into blood culture bottles and were tested for susceptibility to fluconazole directly from the bottles after their being flagged as positive by the blood culture instrument. Minimal inhibitory concentration (MIC) determined by fluorescent flow cytometry (FACS) showed excellent agreement to that determined by macrodilution. Following the seeding experiments, 30 true patient specimens were tested directly from positive blood cultures, and MIC determined by both methods showed excellent agreement. Antifungal susceptibility testing by FACS directly from positive blood culture bottles is a reliable, rapid method for susceptibility testing of Candida to fluconazole. The method allows same-day results, does not require subculture to agar media, and can greatly assist in the selection of appropriate antifungal therapy.     

In vitro activities of voriconazole (UK-109, 496), fluconazole, itraconazole and amphotericin B against 132 non-albicans bloodstream yeast isolates (CANARI study)

The aim was to evaluate the in vitro activity of voriconazole compared with those of amphotericin B, itraconazole and fluconazole against 132 bloodstream isolates of Candida non-albicans and Saccharomyces cerevisiae species. The minimal inhibitory concentrations (MICs) were determined by an adapted National Committee for Clinical Laboratory Standards (NCCLS) M27-A method using RPMI 1640 as test medium supplemented with 2% glucose. MIC end-points were determined with a spectrophotometer after incubation for 48 h at 35 degrees C. Optical density data were used for the calculation of the MIC end-points. For amphotericin B, the end-point was defined as the minimal antifungal concentration that exerts 90% inhibition compared with the control well growth. For the azoles, the end-points were determined at 50% inhibition of growth. Amphotericin B is highly active with 97% of isolates inhibited by < or =1 microg ml(-1). Decreased susceptibility or resistance to fluconazole was the rule among C. krusei, which is intrinsically resistant to fluconazole. For C. glabrata isolates, resistance to fluconazole and itraconazole was measured in 13% and 17% of the isolates respectively. Voriconazole was quite active in vitro against all the isolates with a MIC90% of < or =1 microg ml(-1) and we conclude that it may be useful in the treatment of non-albicans bloodstream infections.