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1.
OBJECTIVES: The aim of the present study was to expand the MIC database for Candida lusitaniae in order to further determine its antifungal susceptibility pattern. METHODS: The activities of amphotericin B, fluconazole, itraconazole, voriconazole and flucytosine were determined in vitro against 80 clinical isolates of C. lusitaniae. A set of 59 clinical isolates of Candida albicans and of 51 isolates of Candida glabrata was included to compare the susceptibilities to amphotericin B. The MICs were determined by Etest with RPMI 1640 agar, and with both this medium and antibiotic medium 3 (AM3) agar for testing of amphotericin B. RESULTS: All isolates were highly susceptible to fluconazole. The susceptibility to itraconazole was good; only 4% of isolates had dose-dependent susceptibility (MICs 0.25-0.5 mg/L). Voriconazole was very active in vitro (100% of isolates were inhibited at < or =0.094 mg/L). Flucytosine MICs ranged widely (0.004->32 mg/L). The set included 19% of flucytosine-resistant isolates. For amphotericin B, 100% of isolates were inhibited at < or =0.75 mg/L (MIC(50) 0.047 mg/L; MIC(90) 0.19 mg/L) and at < or =4 mg/L (MIC(50) 0.25 mg/L; MIC(90) 0.75 mg/L) on RPMI and on AM3, respectively. A single isolate was categorized as resistant to amphotericin B (MIC 0.75 and 4 mg/L on RPMI and on AM3, respectively). Amphotericin B thus appeared very active in vitro against C. lusitaniae. Whatever the test medium, the level of susceptibility of C. lusitaniae to amphotericin B did not differ much from those of C. albicans and C. glabrata. CONCLUSION: C. lusitaniae appears to be susceptible to amphotericin B, azole antifungal agents, and, to a lesser extent, flucytosine.  相似文献   

2.
OBJECTIVES: Several studies have documented the potent in vitro activity of caspofungin against Candida spp. This is of special concern for Candida glabrata infections that are often resistant to many azole antifungal agents and, consequently, difficult to treat. The aim of the present study was to expand the data on the in vitro activity of caspofungin against azole-resistant isolates of C. glabrata. METHODS: A total of 50 clinical isolates of C. glabrata were tested for susceptibility to caspofungin. The isolates were cross-resistant to multiple azoles, including fluconazole, itraconazole, ketoconazole and voriconazole. Expression of the resistance-related CgCDR1 and CgCDR2 genes was evaluated by quantitative RT-PCR analysis. The MICs of caspofungin were determined by using the National Committee for Clinical Laboratory Standards M27-A2 reference method. RESULTS: C. glabrata isolates exhibited increased expression of the CDR efflux pump(s), and this was in accordance with their high-level azole resistance. In contrast, all the isolates were highly susceptible to caspofungin (100% of isolates were inhibited at 相似文献   

3.
The relative growth (percentage of growth relative to control growth) of 496 isolates representing six Candida species was assessed as a means of determining in vitro susceptibilities of the isolates in microdilution plate wells containing single concentrations of each of seven antifungal agents. The relative growth data were highly reproducible. With flucytosine and amorolfine they correlated well with MICs, but for an azole antifungal agent, terconazole, they did not correlate with MICs. Distributions of relative growth percentages for different Candida spp. showed significant differences in species susceptibility to individual agents. For example, C. albicans was less susceptible than the other species to amorolfine; C. parapsilosis isolates were particularly susceptible to terbinafine; and C. glabrata, C. guilliermondii, and C. krusei isolates were less susceptible than C. albicans to fluconazole and ketoconazole but equally susceptible as or more susceptible than C. albicans to itraconazole. Differential patterns of susceptibility to individual azole antifungal agents were noted for some individual strains as well as for Candida spp.  相似文献   

4.
OBJECTIVES: To investigate the in vitro antifungal susceptibility pattern of 375 Candida albicans bloodstream isolates recovered during the European Confederation of Medical Mycology survey of candidaemia performed in Lombardia, Italy and to test the ability to form biofilm. METHODS: In vitro susceptibility to flucytosine, fluconazole, itraconazole, posaconazole, voriconazole and caspofungin was performed by broth microdilution following the NCCLS guidelines. Biofilm production was measured using the XTT reduction assay in 59 isolates selected as representative of different patterns of susceptibility to flucytosine and azoles. RESULTS: MICs (mg/L) at which 90% of the strains were inhibited were < or =0.25 for flucytosine, 0.25 for caspofungin, 4 for fluconazole and 0.06 for itraconazole, voriconazole and posaconazole. Flucytosine resistance was detected in five isolates and was associated with serotype B in 2/29 and serotype A in 3/346. Resistance to fluconazole was detected in 10 isolates; nine of these exhibited reduced susceptibility to the other azoles. Among the 10 patients with fluconazole-resistant C. albicans bloodstream infection, only one, an AIDS patient, had been previously treated with fluconazole. Biofilm production was observed in 23 isolates (39%) and was significantly associated with serotype B. No relationship was detected with the pattern of antifungal susceptibility. CONCLUSIONS: Resistance is uncommon in C. albicans isolates recovered from blood cultures, while biofilm production is a relatively frequent event. Periodic surveillance is warranted to monitor the incidence of in vitro antifungal resistance as well as of biofilm production.  相似文献   

5.
Isavuconazole is the active component of the new azole antifungal agent BAL8557, which is entering phase III clinical development. This study was conducted to compare the in vitro activities of isavuconazole and five other antifungal agents against 296 Candida isolates that were recovered consecutively from blood cultures between 1995 and 2004 at a tertiary care university hospital. Microdilution testing was done in accordance with CLSI (formerly NCCLS) guideline M27-A2 in RPMI-1640 MOPS (morpholinepropanesulfonic acid) broth. The antifungal agents tested were amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and isavuconazole. C. albicans was the most common species, representing 57.1% of all isolates. There was no trend found in favor of non-Candida albicans species over time. In terms of MIC(50)s, isavuconazole was more active (0.004 mg/liter) than amphotericin B (0.5 mg/liter), itraconazole (0.008 mg/liter), voriconazole (0.03 mg/liter), flucytosine (0.125 mg/liter), and fluconazole (8 mg/liter). For isavuconazole, MIC(50)s/MIC(90)s ranged from 000.2/0.004 mg/liter for C. albicans to 0.25/0.5 mg/liter for C. glabrata. Two percent of isolates (C. glabrata and C. krusei) were resistant to fluconazole; C. albicans strains resistant to fluconazole were not detected. There were only two isolates with MICs for isavuconazole that were >0.5 mg/liter: both were C. glabrata isolates, and the MICs were 2 and 4 mg/liter, respectively. In conclusion, isavuconazole is highly active against Candida bloodstream isolates, including fluconazole-resistant strains. It was more active than itraconazole and voriconazole against C. albicans and C. glabrata and appears to be a promising agent against systemic Candida infections.  相似文献   

6.
OBJECTIVES: The antifungal drug susceptibilities of 351 isolates of Candida species, obtained through active laboratory-based surveillance in the period January 2002-December 2003, were determined (Candida albicans 51%, Candida parapsilosis 23%, Candida tropicalis 10%, Candida glabrata 9%, Candida krusei 4%). METHODS: The MICs of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and caspofungin were established by means of the broth microdilution reference procedure of the European Committee on Antibiotic Susceptibility Testing. RESULTS AND CONCLUSIONS: Amphotericin B and flucytosine were active in vitro against all strains. A total of 24 isolates (6.8%) showed decreased susceptibility to fluconazole (MIC > or = 16 mg/L) and 43 (12.3%) showed decreased susceptibility to itraconazole (MIC > or = 0.25 mg/L). Voriconazole and caspofungin were active in vitro against the majority of isolates, even those that were resistant to fluconazole.  相似文献   

7.
OBJECTIVES: The aim of this study is to evaluate the susceptibilities of Candida spp. to the common antifungal agents in a German university hospital. Since quick results of in vitro testing are desirable, Etest and the CLSI broth microdilution (BMD) method (reference method) were compared, focusing on the validity of early readings. METHODS: A total of 512 Candida spp. isolates, including 174 from primarily sterile sites, were collected in the clinical routine. The yeasts were differentiated by CHROMagar and verified by API 20C AUX if necessary. In vitro susceptibilities to amphotericin B, flucytosine, fluconazole, voriconazole and caspofungin were determined using the BMD method described in the CLSI (formerly NCCLS) M27-A2 document and Etest. MICs were noted after 24 and 48 h of incubation. RESULTS: The most frequently isolated species was Candida albicans. Among the non-albicans species, Candida glabrata was the most prevalent, followed by Candida tropicalis, Candida parapsilosis and Candida krusei. MICs (mg/L) at which 90% of the strains were inhibited were 1 for amphotericin B, 32 for flucytosine, 8 for fluconazole, 0.25 for voriconazole and 1 for caspofungin. Susceptibility to fluconazole was 85.0% for C. glabrata and 5.3% for C. krusei, almost all other isolates were susceptible in over 90% except very rare species. The 48 h MIC values of Etest and BMD were in agreement (no more than 2 log(2) dilutions) in 88.7% to 98.1% with categorical agreement rates of 91.6% to 98.2%, depending on the antifungal agent. Comparison of the 24 h MICs of both BMD and Etest with the 48 h MICs of the reference method showed categorical agreement in 94.9% to 99.2%. For caspofungin, however, a comparison of the categorical agreement was not possible due to the lack of interpretive breakpoints. The order of frequency and the resistance patterns of the isolates from primarily sterile sites and those of isolates from non-sterile sites did not differ. CONCLUSIONS: No alarming resistances against the agents tested were found; however, owing to the relatively high frequency of C. glabrata with elevated fluconazole MICs, this species and, to a certain extent, C. krusei must be taken into consideration when choosing antifungal agents for calculated therapy. Etest is a reliable method for the susceptibility testing of Candida spp. and the 24 h readings of both Etest and BMD can serve as helpful preliminary results in most cases.  相似文献   

8.
目的 了解临床分离的念珠菌对氟康唑、两性霉素B、氟胞嘧啶、伊曲康唑及酮康唑体外敏感性。方法 采用SensititreYeastOne试验板以微量稀释法测定上述 5种抗真菌药物对临床分离的 10 8株念珠菌最低抑菌浓度 (MIC)。结果  10 8株念珠菌中达到氟康唑、伊曲康唑、氟胞嘧啶耐药标准的分别有 8株 (7.4%)、15株(13.9%)、2株 (1.9%) ,念珠菌属MIC值分布种间差异较大。白色念珠菌对 5种药物的MIC90 值最低 ,6 0株白色念珠菌中仅 2株耐氟康唑 ,3株耐伊曲康唑 ,对氟胞嘧啶无耐药株 ;光滑念珠菌对氟康唑、伊曲康唑、酮康唑的MIC值分布呈高值 ,10株光滑念珠菌中 4株耐氟康唑 ,3株剂量依赖性敏感 ,7株耐伊曲康唑 ,且吡咯类之间有交叉耐药。其他菌株 ,除季也蒙念珠菌对伊曲康唑有一定的耐药 (2 /6 )外 ,对 5种抗真菌药物的MIC分布均较低。结论 不同念珠菌对常用抗真菌药物敏感性存在差异 ,准确分离鉴定和药敏试验 ,对于指导临床合理选药有重要意义。  相似文献   

9.
Candida species are the most common cause of fungal infections in hospitalized patients. Recent studies have reported a relative reduction in the rates of infection caused by Candida albicans and a shift toward non-albicans Candida spp. Data on the distribution and susceptibility of Candida spp. from children's hospitals are limited. Clinical isolates of Candida were collected from 4 US children's hospitals in 2003. Broth dilution MICs for amphotericin B, fluconazole, voriconazole, caspofungin, posaconazole, and ravuconazole were performed according to National Committee for Clinical Laboratory Standards-approved methodology. A total of 179 clinical isolates were identified and included. Of 179, 77 (43%) were C. albicans. Candida parapsilosis isolates were the second most frequently identified (57/175, 32%), followed by Candida glabrata, Candida tropicalis, and Candida lusitaniae (approximately 8% each). Caspofungin was the most active agent in vitro against all Candida spp. Fluconazole resistance was seen among C. glabrata, C. tropicalis, and Candida krusei isolates. Newer azoles had improved activity against fluconazole-resistant isolates of Candida. Among isolates of C. parapsilosis, nearly 20% were resistant to amphotericin B. The current study highlights the emergence of C. parapsilosis as a distinct pediatric pathogen with clinical and therapeutic implications. Furthermore, our current susceptibility data include newer antifungal agents that appear to be quite active in vitro and may provide new therapeutic options for the treatment of serious yeast infections in children.  相似文献   

10.
Antifungal susceptibilities (NCCLS, approved standard M27-A, 1997) were determined for the reference strain ATCC 90028 and 21 clinical isolates of Candida albicans with varying levels of fluconazole susceptibility using RPMI 1640 (RPMI) and 80% fresh human serum-20% RPMI (serum). Sixty-four percent (14 of 22) of the isolates tested demonstrated significant decreases (> or = 4-fold) in fluconazole MICs in the presence of serum, and the remaining eight isolates exhibited no change. Itraconazole and ketoconazole, two highly protein-bound antifungal agents, had MICs in serum that were increased or unchanged for 46% (10 of 22) and 41% (9 of 22) of the isolates, respectively. All 10 isolates tested against an investigational antifungal agent, LY303366, demonstrated significant increases in the MIC required in serum, while differences in amphotericin B MICs in the two media were not observed. Four of 10 isolates tested demonstrated fourfold higher flucytosine MICs in serum than in RPMI. Postantifungal effects (PAFEs) and 24-h kill curves were determined by standard methods for selected isolates. At the MIC, fluconazole, itraconazole, ketoconazole, flucytosine, and LY303366 kill curves and PAFEs in RPMI were similar to those in serum. Isolates of fluconazole-resistant C. albicans required lower MICs in serum than in RPMI, without relative increases in fungal killing or PAFEs. Isolates tested against amphotericin B demonstrated significantly reduced killing and shorter PAFEs in serum than in RPMI without observable changes in MIC. In conclusion, antifungal pharmacodynamics in RPMI did not consistently predict antifungal activity in serum for azoles and amphotericin B. Generally speaking, antifungal agents with high protein binding exhibited some form of reduced activity (MIC, killing, or PAFE) in the presence of serum compared to those with low protein binding.  相似文献   

11.
OBJECTIVES: To analyse the in vitro antifungal susceptibility of 261 non-albicans Candida bloodstream strains isolated during the European Confederation of Medical Mycology survey of candidaemia performed in Lombardia, Italy (September 1997-December 1999). METHODS: In vitro susceptibility to flucytosine, fluconazole, itraconazole, posaconazole and voriconazole was determined using the broth microdilution method described in the NCCLS M27-A guidelines. Etest strips were used to assess susceptibility to amphotericin B. In vitro findings were correlated with the patient's underlying condition and previous antifungal treatment. RESULTS: MICs (mg/L) at which 90% of the strains were inhibited were, respectively, 2 for flucytosine, 8 for fluconazole, 0.5 for itraconazole, 0.25 for voriconazole and 0.25 for posaconazole. Amphotericin B MIC endpoints were <0.50 mg/L in all the isolates tested. Flucytosine resistance was detected in 19 isolates (7%), mainly among Candida tropicalis strains (30%). Innate or secondary fluconazole resistance was detected in 13 strains (5%). Among the 13 patients with fluconazole-resistant Candida bloodstream infection, three were HIV positive, including one treated with fluconazole for oral candidosis; the four who were HIV negative had received the azole during the 2 weeks preceding the candidaemia. Cross-resistance among fluconazole and other azoles was a rare event. CONCLUSIONS: Resistance is still uncommon in non-albicans Candida species recovered from blood cultures. However, in fungaemias caused by C. tropicalis, Candida glabrata and Candida krusei, there is a high prevalence of resistance to fluconazole and flucytosine. Fluconazole resistance should be suspected in patients treated previously with azoles, mainly those with advanced HIV infection.  相似文献   

12.
13.
In this study the effects of different antifungal agents on the binding of Candida albicans yeast cells to different supports were examined. Pre-treatment with amphotericin B or dithiothreitol (DTT) severely reduced the ability of C. albicans yeasts to bind to plastic, while the effects of pre-treatment with fluconazole, ketoconazole or flucytosine were less marked. Both DTT and amphotericin B reduced the binding of yeasts to bovine serum albumin (BSA) and amino acids at low concentrations, while the other antifungal agents were effective at concentrations several-fold higher than their MICs. These data suggest that DTT and amphotericin B affect the yeast cell wall components, and alter both hydrophobic interactions with plastic, and the more specific interactions with BSA and amino acids. By contrast, the effect of the azoles and flucytosine appears to be largely restricted to hydrophobic interactions.  相似文献   

14.
The use of azole prophylaxis as a measure to prevent invasive fungal infections in high-risk patients is increasing and is now the standard of care in many institutions. Previous studies disagree on whether preexposure of Candida albicans to azoles affects their subsequent susceptibility to amphotericin B (AmB). The present in vitro study indicates that azole exposure generates a subpopulation of cells that are not affected by subsequent exposure to AmB. These cells that are phenotypically resistant to AmB tolerated by most cells not exposed to azole. The percentage of cells that convert to phenotypic resistance to AmB varies with the concentration and the azole. Itraconazole is more effective than fluconazole in generating cells that are phenotypically resistant to AmB and that tolerate an otherwise lethal transient exposure to AmB. Until cells that are not exposed to fluconazole are simultaneously challenged with AmB, they are not protected to a significant extent from killing by AmB. Cells that are challenged with continuous exposure to AmB also acquire phenotypic resistance to AmB at increased frequencies by azole preexposure, but this requires that the azole be continuously present during incubation with AmB. In addition, Candida cells taken from mature colonies that are not actively growing are not susceptible to the short-term killing effects of AmB without azole preexposure. The adaptive responses of C. albicans to AmB and potentially other antifungal agents that may result from prior exposure to azoles in vitro or potentially in microenvironments in vivo that induce physiological changes may have major clinical implications.  相似文献   

15.
The impact of prolonged antifungal therapy on the development of resistance was examined in 61 patients with oropharyngeal thrush. Fifty-nine patients had symptomatic human immunodeficiency virus infection, one had lung cancer, and one had metastatic prostate cancer. Cultures of pharyngeal samples from all patients were positive for yeasts and included 57 (93.4%) Candida albicans, 3 (4.9%) Candida glabrata, and 1 (1.6%) Candida krusii. Of 61 patients, 32 (52.5%) were receiving or had recently received antifungal therapy. Clotrimazole was the most commonly prescribed azole, followed by ketoconazole and fluconazole. Two patients had received amphotericin B therapy and one had received flucytosine. The duration of therapy with clotrimazole, ketoconazole, and fluconazole ranged from 3 to 240, 14 to 44, and 7 to 138 days, respectively. There was no overall difference in the susceptibilities of the clinical isolates from treated and untreated patients to amphotericin B, nystatin, flucytosine, clotrimazole, ketoconazole, and fluconazole. A.C. albicans isolate from one patient who had clinically failed on ketoconazole, fluconazole, and amphotericin B was resistant to these drugs. The lack of difference in the susceptibility pattern indicates that clinically significant emergence of resistance does not occur in those patients who receive prolonged antifungal therapy.  相似文献   

16.
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).  相似文献   

17.
目的 分析医院内感染假丝酵母菌菌种构成和耐药性。 方法 对临床标本分离的酵母样真菌,用VITEK-Ⅱ(生物梅里埃公司)生化鉴定仪、API20c生化鉴定试纸条和念珠菌显色琼脂以及聚合酶链反应(polymerase chain reaction, PCR)方法进行酵母样真菌菌种的鉴定,应用ATB Fungus3 进行药敏试验。 结果 96株酵母样真菌,可分为6个种,包括白色念珠菌40株 (41.7%)、热带念珠菌36株 (37.5%)、光滑念珠菌13株 (13.54%)、近平滑念珠菌5株 (5.21%)、克柔念珠菌1株 (1.04%)、挪威念珠菌 1株(1.04%)。各种假丝酵母菌对5种抗真菌药呈现不同的敏感性,对两性霉素B和5-氟胞嘧啶的敏感率为100%,而对氟康唑、伊曲康唑、伏立康唑则表现出一定的耐药性。 结论 基因间隔转录区分子生物学分析结合传统培养和生化方法,可有效提高假丝酵母菌鉴定的准确性。本研究结果提示医院内非白假丝酵母菌感染有增多趋势。重症监护病房(intensive care unit, ICU)是重要的假丝酵母菌来源科室。60岁以上的老龄患者是医院内真菌感染的高危人群。体外药敏试验提示部分假丝酵母菌出现了唑类药物(氟康唑和伊曲康唑)的耐药性。  相似文献   

18.
The relative growth (percentage of growth relative to control growth) of 767 Candida isolates representing five species was measured in microcultures at 25 and 37 degrees C. In the presence of 10(-4) M flucytosine, the distribution of relative yeast growth data indicated that Candida albicans isolates were less susceptible at 25 degrees C than at 37 degrees C, while the opposite was found with 4 x 10(-5) M amorolfine for most of the isolates tested. Repetition of the experiments at four different temperatures with 99 C. albicans isolates and five antifungal agents confirmed a direct relationship between growth inhibition and increasing temperature from 25 to 40 degrees C with amphotericin B, flucytosine, and terconazole; a strong inverse relationship between inhibition and temperature with amorolfine; and a weak inverse relationship with terbinafine. However, these relationships were not always noted with other Candida spp.: in particular, the growth of C. glabrata and C. parapsilosis isolates tended to be greater at 37 degrees C than at 25 degrees C in the presence of the azole-derivative antifungal agents itraconazole and terconazole. These findings stress the species-specific individuality of yeast susceptibility to azole antifungal agents. The results with C. albicans and amorolfine and terbinafine accord with their known in vivo efficacy in mycoses involving low-temperature superficial sites and poor activity against mycoses involving deep body sites. The data also reinforce the need for control of experimental variables such as temperature in the design of standardized yeast susceptibility tests.  相似文献   

19.
We assessed the distribution, antifungal susceptibility, and treatment associated with 161 non-Candida albicans isolates recovered from hospitalized patients over a 6-month period. The three most prevalent species were C. glabrata (100), C. tropicalis (28), and C. krusei (15). Resistance of C. glabrata to fluconazole and itraconazole were 6% and 17% respectively; 80% of the fluconazole-resistant isolates were cross-resistant to itraconazole. Prior azole exposure significantly reduced azole susceptibility in C. glabrata and also affected its subsequent selection among colonized patients. Only 21% of the patients had clinical infections. Patients with fungemia were more likely to be treated with amphotericin versus an azole. Overall treatment success was higher in patients treated with amphotericin versus an azole (56% vs 31%). Routine susceptibility testing on all Candida species does not appear necessary except where therapy with an azole is being considered to detect resistant isolates or for epidemiologic surveillance purposes. Further studies are needed to delineate the relationship between azole MICs and treatment outcomes of invasive candidiasis due to non-C. albicans species.  相似文献   

20.
OBJECTIVES: Candidiasis can be associated with the formation of biofilms on bioprosthetic surfaces and the intrinsic resistance of Candida albicans biofilms to the most commonly used antifungal agents has been demonstrated. In this study, we report on the antifungal activity of caspofungin at two different concentrations, on C. albicans and Candida parapsilosis biofilms with different ages of maturation. METHODS: Fifteen strains of C. albicans (10 strains susceptible to fluconazole in vitro and five strains resistant to this antifungal agent) and six strains of C. parapsilosis (all were susceptible to fluconazole in vitro) were studied. The antifungal activity of caspofungin was assessed by looking for a significant inhibition of the metabolic activity of yeasts within biofilms. Biofilms of Candida were produced in vitro, on silicone catheters. RESULTS: Caspofungin used at MIC did not modify the metabolic activity of C. albicans, whatever the maturation age of the biofilms. The same concentration of caspofungin significantly reduced the metabolism (P相似文献   

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