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In-vitro activity of five antifungal agents against uncommon clinical isolates of Candida spp.

A broth microdilution method and an agar dilution method were used for testing fluconazole, itraconazole, ketoconazole, flucytosine and amphotericin B against 98 clinical isolates belonging to seven species of Candida. The approximate rank order of fluconazole MICs was Candida lusitaniae approximately Candida kefyr < Candida famata approximately Candida guilliermondii < Candida pelliculosa approximately C. lipolytica approximately Candida inconspicua. Candida lypolitica and C. pelliculosa were the species least susceptible to itraconazole and ketoconazole. Flucytosine MICs revealed the highest prevalence of resistant strains among C. lipolytica and C. lusitaniae. All isolates were susceptible to amphotericin B.

Amphotericin B↗

Antifungal susceptibilities of Candida spp. isolated from blood in Spain and Argentina, 1996-1999.

The aim of this study was to identify retrospectively trends in species distribution and susceptibility patterns of Candida species causing bloodstream infections in 99 medical centres (55 in Spain and 44 in Argentina) from 1996 to 1999. A total of 744 Candida isolates were sent to the mycology reference laboratories during the study period (514 to the Spanish laboratory and 230 to the Argentinian laboratory). Candida non-albicans strains caused more episodes of fungaemia than Candida albicans isolates in both Spain and Argentina. C. albicans was isolated in 30.2% (155/514) and 40.9% (94/230) of episodes in Spain and in Argentina, respectively. In addition, Candida parapsilosis was the second most commonly isolated pathogen (36.4%). Candida tropicalis caused 13.7% of infections and Candida glabrata 7.4%. The amphotericin B MIC was <or=1 mg/L for 97.5% of isolates, and 8.3% of strains had decreased susceptibility to flucytosine. Regarding susceptibility to azole agents, 9.9% (74/744) and 21.9% (163/744) exhibited decreased susceptibility to fluconazole and itraconazole, respectively. For Candida species, some marked differences were found between countries, and decreased susceptibility to azole agents was detected significantly more frequently (P < 0.05) among Argentinian isolates of C. albicans, C. parapsilosis and C. tropicalis. These findings reinforced the need for continued surveillance programmes to analyse the factors that may have an influence on candidaemia incidence. Susceptibility patterns were obtained by means of the proposed reference procedure for antifungal susceptibility testing of the European Committee on Antibiotic Susceptibility Testing (EUCAST). Excellent interlaboratory agreement was achieved for MICs for quality control strains noted in Spain and in Argentina (intraclass correlation coefficient of 0.97), indicating that the EUCAST procedure is a reliable methodology for susceptibility testing.

Antifungal Agents↗

Comparison of three methods for in vitro susceptibility testing of Candida species with flucytosine.

Optimal methods for susceptibility testing of Candida spp. with flucytosine have not been determined. Breakpoints were recommended in 1984, but never validated. In this study, we compared the 1984 recommended macrodilution broth method (using an 80% endpoint) with a modification of the more recent NCCLS-recommended microdilution broth method with three endpoints-spectrophotometric 50% and 80% and a no growth endpoint determined by eye. NCCLS and British Society for Medical Mycology (BSMM) breakpoints were also compared. One hundred and fifty isolates comprised of Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Candida parapsilosis and Candida lusitaniae were tested. Reproducibility was excellent. For C. albicans (n = 65), the correlation between tests was excellent (>75%), with few major discrepancies (<5%). For C. tropicalis (n = 27), correlation was good (59%), but there were a small number of major discrepancies (up to 11%, depending on breakpoint used). Results by the broth macrodilution method were generally higher than both microdilution methods for C. glabrata (n = 16; correlation of 18.8%), but only one major discrepancy was seen. Ten of the 11 C. parapsilosis isolates tested were susceptible by all methods, regardless of breakpoint chosen, with a correlation of 18.2%, but no major discrepancies were seen. A correlation between all methods (50%) was seen with C. lusitaniae (n = 10), with many isolates resistant or intermediate. In contrast, correlation between methods for C. krusei was poor (<5%); NCCLS microtitre modification produced results that were classified as intermediate or resistant, regardless of the breakpoint used. The methodology for susceptibility testing C. albicans is robust. Additional work to optimize susceptibility testing with flucytosine is necessary for non-albicans Candida species, especially C. krusei.

Antifungal Agents↗

Stable susceptibility of Candida blood isolates to fluconazole despite increasing use during the past 10 years.

The prevalence of drug-resistant bacterial pathogens is very high in Taiwan. Accordingly, there was great concern that the introduction of fluconazole would result in rapid emergence of drug-resistant yeasts. Thus, we recommended in 1991 that fluconazole be used for treatment only. To explore the impact of this policy fluconazole susceptibility of Candida species blood culture isolates and outcome of patients with nosocomial candidaemia were monitored prospectively at National Taiwan University Hospital during 1994-2000. The MICs of fluconazole were determined by the disc diffusion method. There were 1095 episodes of nosocomial candidaemia during 1994-2000. Candida albicans was the most common species (50.4%), followed by Candida tropicalis (20.5%), Candida parapsilosis (14.2%) and Candida glabrata (12.0%). There were 0-2 isolates of Candida krusei per year. The incidence of nosocomial candidaemia and the proportion of C. glabrata peaked in 1996 and decreased thereafter. Fluconazole susceptibility was determined for 552 Candida blood isolates. Only 0.7% of blood isolates were resistant to fluconazole. Fluconazole susceptibility was 94.0% in 1994-1995 and 97.9% in 1999-2000 (P = 0.06). Attributable mortality for patients with nosocomial candidaemia was 43.2% in 1994-1995 and was 25% in 2000 (P = 0.005). Despite an increase in the incidence of nosocomial fungal infection and increased consumption of fluconazole from 1994 to 2000, there was no significant change in the susceptibility to fluconazole for bloodstream isolates of Candida species. These findings appear to be attributed to several factors. These include low prevalence of C. krusei and C. glabrata, changing patterns of use of antifungal drugs and broad-spectrum antibiotics, and efforts to improve the rational use of antifungal agents at our hospital.

Antifungal Agents↗

Invasive Candida species infections: a 5 year population-based assessment.

OBJECTIVES: Candida species have emerged as important causes of invasive infections and rates of resistance to standard antifungal therapies are rising. The objective of this study was to define the occurrence of, risk factors for, and antifungal susceptibilities of invasive Candida species infections in a large Canadian health region. METHODS: Population-based surveillance was conducted for invasive Candida species infections in the Calgary Health Region during a 5 year period and susceptibility testing was performed. RESULTS: The annual incidence of invasive Candida species infection was 2.9 per 100,000 population (0.2 and 2.8 per 100,000 for central nervous system and bloodstream infection, respectively). The very young and elderly were at highest risk for invasive Candida species infections. Several risk factors for developing invasive Candida species infection were identified with chronic haemodialysis, organ transplant recipient, and cancer patients at highest risk. Thirty percent (56/184; 43 susceptible, dose-dependent and 13 resistant) of isolates demonstrated reduced susceptibility to fluconazole. Only one (1%) isolate had reduced susceptibility to amphotericin B and six (3%) and three (2%) isolates had minimum inhibitory concentrations of >or=1 mg/L to voriconazole and caspofungin, respectively. Overall, 40% of patients died in-hospital for an annual mortality rate of 1.2 per 100,000. CONCLUSIONS: Candida species are an important cause of invasive infection and patients with co-morbidities and extremes of age are at highest risk. Alternatives to fluconazole should be considered for initial empiric therapy in patients with severe invasive Candida species infections.

Antifungal Agents↗

Activity of novel non-amphipathic cationic antimicrobial peptides against Candida species.

BACKGROUND AND OBJECTIVES: Candida species are problematic opportunistic pathogens in the hospital setting, where they are frequently associated with opportunistic infections of indwelling medical devices. There are only a few effective classes of antifungal agents currently available, and some species, such as Candida lusitaniae, Candida glabrata and Candida krusei, are intrinsically resistant to some of these drugs, further reducing existing therapeutic options. We have recently developed synthetic, non-amphipathic cationic antimicrobial peptides (CAPs) based on the structure of native hydrophobic membrane-spanning domains of integral membrane proteins. In this article, we report on the activity of these CAPs and new variants thereof against eight Candida species. METHODS AND RESULTS: Using a combination of MIC, haemolysis, time-kill and biofilm killing assays, we demonstrate activity of CAPs in the micromolar range against eight Candida species, with little toxicity to mammalian cells. The synthetic peptides killed both the fluconazole-susceptible and fluconazole-resistant strains of Candida albicans, Candida tropicalis and C. glabrata by 4 logs or more within 3 h, and also killed pre-formed yeast biofilms on plastic surfaces. CONCLUSIONS: These peptides show promise as a basis for development of novel, broad-spectrum antimicrobial agents.

Antifungal Agents↗

Candida hepatitis. Histopathologic diagnosis.

Candida hepatitis, usually a manifestation of disseminated candidiasis in immunocompromised patients, is difficult to diagnose antemortem. We studied six patients with proven hepatic candidiasis to assess features helpful in deriving a correct diagnosis. Five patients were immunosuppressed as a result for treatment for leukemia; one was immunosuppressed due to renal transplantation. All had sustained fevers greater than 101 degrees F, elevated alkaline phosphatase levels, and multiple hepatic and splenic defects--presumably abscesses--on abdominal CT scan. Twelve liver biopsies (nine needle, three wedge) were examined. Biopsies from four patients contained identifiable Candida organisms within suppurative granulomas; a biopsy from a fifth patient grew Candida albicans in cultures. In the sixth patient, the first biopsy was culture positive for Candida albicans, and the second biopsy, a fine-needle aspirate, contained Candida organisms and purulent material. In all of the nondiagnostic biopsies, as well as in regions of the diagnostic biopsies around the suppurative granulomas, mass-associated obstructive changes were noted. These included pericentral sinusoidal dilatation and cholestatic inflammation characterized by periportal ductular proliferation with surrounding neutrophils and edema. We conclude that in the appropriate clinical setting, these mass-associated histologic findings are suggestive of adjacent Candida abscesses. Definite diagnosis requires either the identification of Candida organisms within inflammatory hepatic lesions or positive culture of Candida from the liver biopsy.

Adolescent↗

Risk factors for Candida species colonization of neonatal intensive care unit patients.

BACKGROUND: Candida spp. are increasingly important pathogens in neonatal intensive care units (NICU). Prior colonization is a major risk factor for candidemia, but few studies have focused on risk factors for colonization, particularly in NICU patients. METHODS: A prospective, multicenter cohort study was performed in six NICUs to determine risk factors for Candida colonization. Infant gastrointestinal tracts were cultured on admission and weekly until NICU discharge and health care worker hands were cultured monthly for Candida spp. RESULTS: The prevalence of Candida spp. colonization was 23% (486 of 2157 infants); 299 (14%), 151 (7%) and 74 (3%) were colonized with Candida albicans, Candida parapsilosis and other Candida spp., respectively. Multiple logistic regression analysis adjusting for length of stay, birth weight < or = 1000 g and gestational age < 32 weeks revealed that use of third generation cephalosporins was associated with either C. albicans (155 incident cases) or C. parapsilosis (104 incident cases) colonization. Use of central venous catheters or intravenous lipids were risk factors for C. albicans, whereas delivery by cesarean section was protective. Use of H2 blockers was an independent risk factor for C. parapsilosis. Of 2989 cultures from health care workers' hands, 150 (5%) were positive for C. albicans and 575 (19%) for C. parapsilosis, but carriage rates did not correlate with NICU site-specific rates for infant colonization. CONCLUSIONS: We speculate that NICU patients acquire Candida spp., particularly C. parapsilosis, from the hands of health care workers. H2 blockers, third generation cephalosporins and delayed enteral feedings alter gastrointestinal tract ecology, thereby facilitating colonization.

Candida↗

Taxonomic relationships among the taxa in the Candida guilliermondii complex, as revealed by comparative electrophoretic karyotyping.

Electrophoretic karyotypes of 15 type strains of the taxa in the Candida guilliermondii complex including Candida fukuyamaensis Nakase et al. and Candida xestobii Yarrow et S. A. Meyer were comparatively analysed by using the CHEF (contour-clamped homogeneous electric field) method of PFGE. Eighteen strains (isolated from various natural sources in China) which were originally identified as C. guilliermondii by conventional methods were also included. Six electrophoretic karyotype groups were recognized among the strains compared. The following type strains were grouped together with the type strains of C. guilliermondii (Castellani) Langeron et Guerra and Pichia guilliermondii Wickerham: Blastodendrion arztii Ota, Blastodendrion krausi Ota, Candida amidovorans Balloni et al., C. guilliermondii var. japonica Sugiyama et Goto, Candida mamillae S. Goto, Candida parapsilosis (Ashford) Langeron et Talice var. tokyoensis Suzuki et al., C. parapsilosis var. tuxtlensis Herrera et al. and six Chinese strains. The type strain of Torulopsis kestonii Scarr et Rose was classified into the group together with the type strain of Candida fermentati (Saito) Bai and seven Chinese strains. The group represented by the type strain of C. fukuyamaensis included five other strains isolated in China. The type strains of Candida xestobii, C. guilliermondii var. carpophila Phaff et M. W. Miller and Trichosporon appendiculare Batista et al. were separated into three different groups, respectively. Taxonomic relationships among the taxa studied are discussed.

Candida↗

Genetic relatedness of Candida strains isolated from women with vaginal candidiasis in Malaysia.

The aims of this study were to compare the genetic relatedness of: (i) sequential and single isolates of Candida strains from women with recurrent vaginal candidiasis (RVC); and (ii) Candida strains from women who had only one episode of infection within a 1-year period. In total, 87 isolates from 71 patients were cultured, speciated and genotyped by random amplification of polymorphic DNA (RAPD) analysis. Patients were categorized into three groups, namely those with: (i) a history of RVC from whom two or more yeast isolates were obtained (group A); (ii) a history of RVC from whom only a single isolate was obtained (group B); and (iii) a single episode of vaginal candidiasis within a 1-year period (group C). Six yeast species were detected: Candida albicans, Candida glabrata, Candida lusitaniae, Candida famata, Candida krusei and Candida parapsilosis. Interestingly, the prevalence of non-albicans species was higher in group A patients (50 %) than in patients in groups B (36 %) or C (18.9 %). Eighty RAPD profiles were observed, with a total of 61 polymorphic PCR fragments of distinct sizes. Clustering analysis showed that, overall, the majority of patients in group A had recurrent infections caused by highly similar, but not identical, sequential strains [mean pairwise similarity coefficient (S(AB)) = 0.721 +/- 0.308]. The range of mean S(AB) values for intergroup comparisons for C. albicans isolates alone was 0.50-0.56, suggesting that there was no significant relatedness between strains from different groups. Genetic similarity of C. albicans isolates from patients in group A was lower than that of C. albicans isolates from patients in group C (mean S(AB) = 0.532 +/- 0.249 and 0.636 +/- 0.206, respectively); this difference was statistically significant (P = 0.036). These results demonstrate that the cause of recurrent infections varies among individuals and ranges between strain maintenance, strain microevolution and strain replacement; the major scenario is strain maintenance with microevolution. They also show that C. albicans strains that cause recurrent infections are less similar to each other than strains that cause one-off infections, suggesting that the former may represent more virulent subtypes.

Candida↗

Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells.

Infection by the human opportunistic fungal pathogen Candida albicans has been increasing over recent years. In an attempt to understand the molecular mechanism of Candida invasion across host tissues, the relationship of C. albicans enolase to human plasminogen/plasmin was investigated. C. albicans enolase is a cell-surface protein and an immunodominant antigen in infected patients' sera. Plasminogen is an abundant plasma protein. Several lines of evidence support the binding of C. albicans enolase to human plasminogen. Firstly, it was found that various Candida strains were able to bind to plasminogen and its active form, plasmin. Secondly, recombinant Candida enolase was retained in a nickel-chelating affinity column matrix that can bind (125)I-labelled plasminogen or plasmin in a dose-dependent manner. Plasmin(ogen)-specific inhibitors, such as epsilon -aminocaproic acid and aprotinin, can effectively block plasmin-binding activity. Thirdly, as with many plasminogen receptors, binding of Candida enolase to plasmin(ogen) is lysine-dependent, whereas little inhibition occurred with arginine, aspartate and glutamate. Fourthly, immobilized enolase enhanced plasminogen's affinity for streptokinase at least tenfold, as demonstrated by its activation of plasmin activity. To elucidate the biological significance of this result, it was demonstrated that the plasmin(ogen)-bound Candida cells were able to induce fibrinolysis activity in a matrix-gel assay. Furthermore, plasmin-bound Candida cells had an increased ability to cross an in vitro blood-brain barrier system. The results given here indicate that Candida enolase is a plasminogen- and plasmin-binding protein and that the interaction of C. albicans enolase with the plasminogen system may contribute to invasion of the tissue barrier.

Blood Vessels↗

In vitro evaluation of virulence attributes of Candida spp. isolated from patients affected by diabetes mellitus.

BACKGROUND: Diabetes mellitus is a common disease found worldwide and it has been previously suggested that oral candidal infections may be more frequent or severe in patients with this disease. Systemic and local factors may influence the balance between the host and yeasts, and favour the transformation of Candida isolates from commensal to pathogenic microorganisms. Candida species have developed specific virulence mechanisms that confer the ability to colonise host surfaces, to invade deeper host tissue, or to evade host defences. Few studies have investigated the expression of the virulence attributes of oral Candida isolates in patients with diabetes mellitus. MATERIAL AND METHODS: The in vitro extracellular proteinase production and the in vitro ability to adhere to fibronectin of 229 Candida isolates of two geographic different groups of patients with diabetes mellitus and of healthy subjects were assessed. RESULTS: Candida isolates of patients with diabetes mellitus expressed a higher ability to adhere than those of healthy subjects. Higher levels of adhesion were also recorded in patients with a lower oral Candida colonisation. No differences were observed in the in vitro expression of extracellular proteinase of Candida isolates of patients with diabetes mellitus and those of non-diabetic subjects. Isolates of patients with type 2 diabetes mellitus expressed greater levels of proteinase than isolates of type 1 diabetes mellitus. CONCLUSIONS: Diabetes mellitus could be considered as an additional variable that may influence not only oral Candida carriage but also the ability of isolates to enhance the expression of virulence attributes.

Candida↗

Candida and squamous (pre)neoplasia of immigrants and Dutch women as established in population-based cervical screening.

The objective of this study was to establish the relationship between Candida vaginalis and (pre)neoplasia and the prevalence of Candida and (pre)neoplasia related to age and ethnicity. Data were collected from 445,671 asymptomatic women invited for mass screening between 1995 and 2002 and coded according to the Dutch cervical smear coding system (KOPAC) with six grades for (pre)neoplastic changes. Prevalence and relative risks (RRs) were established for Candida and squamous abnormalities in Dutch women and four groups of immigrants. The prevalence of Candida is significantly higher in the cohort of 30-year-old women and lower in the cohorts of 45-, 50-, 55-, and 60-year-old women. The RR of having Candida was higher for Surinamese women (1.24; CI 1.08-1.42). Furthermore, the RR of having mild dysplasia was higher for Surinamese women (1.47; CI 1.14-1.89) and for women born in other countries than in The Netherlands, Turkey, and Morocco (1.36; CI 1.13-1.62). No statistically significant relationship between (pre)neoplasia and Candida was observed. C. vaginalis is more frequent among Surinamese women. Presence of Candida is not associated with an increased risk for squamous abnormalities; therefore, women carrying Candida are not at an increased risk of developing cervical cancer.

Adult↗

Six new anamorphic ascomycetous yeasts near Candida tanzawaensis.

Six new species of the yeast genus Candida are described from their unique nucleotide sequences in the D1/D2 domain of 26S rDNA. Five of these species form a clade with Candida tanzawaensis, and the sixth is basal to this group. The new species and their sources of isolation are the following: Candida ambrosiae (type strain NRRL YB-1316, CBS 8844), from insect frass, rotted wood and mushroom fruiting bodies; Candida canberraensis (type strain NRRL YB-2417, CBS 8846), from soil; Candida caryicola (type strain NRRL YB-1499, CBS 8847), from a pignut hickory tree; Candida prunicola (type strain NRRL YB-869, CBS 8848), from exuded gum of a black cherry tree; Candida pyralidae (type strain NRRL Y-27085, CBS 5035), from insect frass; Candida xylopsoci (type strain NRRL Y-27066, CBS 6037), from insect frass.

Animals↗

Combined effect of amphotericin B and rifampin on Candida species.

Synergism with the combination of rifampin and amphotericin B in vitro has been demonstrated with a limited number of Candida strains. To extend these studies (particularly at clinically achievable levels of rifampin), we evaluated the in vitro combined activity of serial twofold dilutions of amphotericin B (0.1 to 6.0 microgram/ml) against 11 concentrations of rifampin (0.2 to 200 microgram/ml) for 40 strains of Candida: 20 Candida albicans, 7 Candida parapsilosis, 8 Candida tropicalis, 2 Candida stellatoidea, 2 Candida guilliermondii, and 1 Candida krusei by using a modified checkerboard microtitration technique. An additive or synergistic effect was seen for 45% of strains with 6.25 microgram of rifampin per ml added to amphotericin B. Whereas the minimal inhibitory concentration to amphotericin B alone was 0.4 microgram/ml or less for 50% of the strains, the percentage increased to 90 with the addition of 6.25 microgram of rifampin per ml. A similar effect was seen with killing: 25% of the strains were killed by 0.4 microgram or less of amphotericin B alone per ml, and 75% of the strains were killed with the addition of 6.25 microgram of rifampin per ml. In vivo studies are needed for confirmation of the usefulness of combined amphotericin B and rifampin therapy.

Amphotericin B↗

Azasordarins: susceptibility of fluconazole-susceptible and fluconazole-resistant clinical isolates of Candida spp. to GW 471558.

The in vitro activity of the azasordarin GW 471558 was compared with those of amphotericin B, flucytosine, itraconazole, and ketoconazole against 177 clinical isolates of Candida spp. GW 471558 showed potent activity against Candida albicans, Candida glabrata, and Candida tropicalis, even against isolates with decreased susceptibility to azoles. Candida krusei, Candida parapsilosis, Candida lusitaniae, and Candida guilliermondii are resistant to GW 471558 in vitro (MICs, >128 microg/ml).

Antifungal Agents↗

Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins.

Biofilms, likely the predominant mode of device-related microbial infection, exhibit resistance to antimicrobial agents. Evidence suggests that Candida biofilms have dramatically reduced susceptibility to antifungal drugs. We examined antifungal susceptibilities of Candida albicans and Candida parapsilosis biofilms grown on a bioprosthetic model. In addition to conventional agents, we determined if new antifungal agents (triazoles, amphotericin B lipid formulations, and echinocandins) have activities against Candida biofilms. We also explored effects of preincubation of C. albicans cells with subinhibitory concentrations (sub-MICs) of drugs to see if they could modify subsequent biofilm formation. Finally, we used confocal scanning laser microscopy (CSLM) to image planktonic- and biofilm-exposed blastospores to examine drug effects on cell structure. Candida biofilms were formed on silicone elastomer and quantified by tetrazolium and dry weight (DW) assays. Susceptibility testing of fluconazole, nystatin, chlorhexidine, terbenafine, amphotericin B (AMB), and the triazoles voriconazole (VRC) and ravuconazole revealed resistance in all Candida isolates examined when grown as biofilms, compared to planktonic forms. In contrast, lipid formulations of AMB (liposomal AMB and AMB lipid complex [ABLC]) and echinocandins (caspofungin [Casp] and micafungin) showed activity against Candida biofilms. Preincubation of C. albicans cells with sub-MIC levels of antifungals decreased the ability of cells to subsequently form biofilm (measured by DW; P < 0.0005). CSLM analysis of planktonic and biofilm-associated blastospores showed treatment with VRC, Casp, and ABLC resulted in morphological alterations, which differed with each agent. In conclusion, our data show that Candida biofilms show unique susceptibilities to echinocandins and AMB lipid formulations.

Amphotericin B↗

Antifungal susceptibilities of clinical isolates of Candida species, Cryptococcus neoformans, and Aspergillus species from Taiwan: surveillance of multicenter antimicrobial resistance in Taiwan program data from 2003.

The susceptibilities of nonduplicate isolates to six antifungal agents were determined for 391 blood isolates of seven Candida species, 70 clinical isolates (from blood or cerebrospinal fluid) of Cryptococcus neoformans, and 96 clinical isolates of four Aspergillus species, which were collected in seven different hospitals in Taiwan (as part of the 2003 program of the study group Surveillance of Multicenter Antimicrobial Resistance in Taiwan). All isolates of Candida species other than C. glabrata and C. krusei were susceptible to fluconazole. Among the 59 C. glabrata isolates, 16 (27%) were not susceptible to fluconazole, and all were dose-dependently susceptible or resistant to itraconazole. For three (5.1%) C. glabrata isolates, voriconazole MICs were 2 to 4 microg/ml, and for all other Candida species isolates, voriconazole MICs were </=0.5 microg/ml. The proportions of isolates for which amphotericin B MICs were >/=2 microg/ml were 100% (3 isolates) for C. krusei, 11% (23 of 207 isolates) for Candida albicans, 3.0% (2 of 67 isolates) for Candida tropicalis, 20% (12 of 59 isolates) for C. glabrata, and 0% for both Candida parapsilosis and Candida lusitaniae. For three (4%) Cryptococcus neoformans isolates, fluconazole MICs were >/=16 microg/ml, and two (3%) isolates were not inhibited by 1 mug of amphotericin B/ml. For four (4.2%) of the Aspergillus isolates, itraconazole MICs were 8 microg/ml. Aspergillus flavus was less susceptible to amphotericin B, with the MICs at which 50% (1 microg/ml) and 90% (2 microg/ml) nsrsid417869\delrsid7301351 of isolates were inhibited being twofold greater than those for Aspergillus fumigatus and Aspergillus niger. All Aspergillus isolates were inhibited by </=1 microg of voriconazole/ml, including isolates with increased resistance to amphotericin B and itraconazole. This study revealed the emergence in Taiwan of decreased susceptibilities of Candida species to amphotericin B and of C. neoformans to fluconazole and amphotericin B. Voriconazole was the most potent agent against the fungal isolates tested, including fluconazole- and amphotericin B-nonsusceptible strains.

Antifungal Agents↗