The postantifungal effect (PAFE) of itraconazole, in comparison with those of miconazole and fluconazole, on Candida Species

To study the postantifungal effect (PAFE) of itraconazole (ITCZ) against Candida species, we quantitated it using a newly introduced parameter T/C(T=time required for the drug-treated culture to reach 5-fold increase in turbidity; C=time required for the drug-free control culture to reach 5-fold increase in turbidity) referred as PAFE index and compared the results with those obtained for two other azole antifungal drugs fluconazole (FLCZ) and miconazole (MCZ). The mean values of PAFE index for ITCZ against three C. albicans strains were 1.28, 1.45, and 1.60 when exposed to the drug for 1 hr at concentrations of 1 x MIC, 2 x MIC and 4 x MIC, respectively. These values are similar to those for MCZ and appreciably higher than those for FLCZ. PAFE index values for ITCZ against each single strain of three non-albicans Candida species exposed to 2 x MIC of the drug for 1 hr were: 1.22 with C. glabrata, 1.63 with C. parapsilosis, and 3.90 with C. tropicalis. Again, comparable values were obtained for MCZ and lower values for FLCZ. The drug concentration for exposure and the duration of exposure only slightly or scarcely affected the PAFE of ITCZ, although the magnitude of the PAFE considerably varied among different strains or species tested. In general, ITCZ, as well as MCZ, produced greater extents of PAFE than those for FLCZ against C. albicans and several non-albicans Candida species.     

Comparative evaluation of Trichosporon asahii susceptibility using ASTY colorimetric microdilution and CLSI M27‐A2 broth microdilution reference methods

The in vitro activity of AMPH‐B, 5‐FC, FLCZ, MCZ, ITCZ, and VRCZ against 50 isolates of T. asahii was determined using CLSI M27‐A2 microdilution and ASTY colorimetric methods. Observed agreement ranged from 96 to 100% according to the drug. Overall, the agreement between two methods was 97.7%. The ASTY colorimetric method was thus determined to be comparable to the CLSI reference method when testing the susceptibility of T. asahii to a variety of antifungal agents.     

In-vitro activity of 5-fluorocytosine against 1,021 Spanish clinical isolates of Candida and other medically important yeasts

The aim of this study was to determine the prevalence of primary resistance to 5-fluorocytosine (5FC) among clinical isolates of yeasts in Spain where this drug is not currently available for therapy. We have tested the in vitro activity of 5FC against 1,021 recent yeast clinical isolates, including 522 Candida albicans, 140 Candida parapsilosis, 68 Candida glabrata, 41 Candida dubliniensis, 50 Candida guilliermondii, 34 Candida tropicalis, 28 Candida krusei, 20 Candida famata, 11 Cryptococcus neoformans, 5 Cryptococcus albidus, 43 Rhodotorula spp., 24 Trichosporon spp., 5 Saccharomyces cerevisiae, 9 Pichia spp., and 21 isolates from other 11 yeast species. The MICs were determined by the ATB Fungus agar microdilution test (bioMerieux, France) and the following interpretive breakpoints were used: susceptible, > 4 microg/ml; intermediate, 8 to 16 microg/ml; resistant, > 32 microg/ml. 5FC was very active against Candida spp. and other medically important yeasts as 852 (83.4%) of the studied isolates were susceptible (MIC < 4 microg/ml). The species most susceptible to 5FC were C. dubliniensis (100%of isolates; MIC90, 0.25 microg/ml), C. famata (100% of isolates; MIC90, 0.25 microg/ml), C. guilliermondii (98%of isolates; MIC90, 0.25 microg/ml), C. glabrata (95.5% of isolates; MIC90, 0.25 microg/ml), and C. neoformans (90.9% of isolates; MIC90, 2 microg/ml). Primary resistance to 5FC was very uncommon, and a MIC > 32 microg/ml, indicator of in vitro resistance, was observed in 106 isolates (10.4%): 77 C. albicans (16.5% of isolates; MIC90, > 128 microg/ml), 9 C. parapsilosis (6.4% of isolates; MIC90, 8 microg/ml), 4 C. albidus (80% of isolates, MIC50, > 128 microg/ml), 3 C. glabrata (4.4% of isolates; MIC90, 0.25 microg/ml), 3 C. tropicalis (8.8% of isolates; MIC90, 4 microg/ml), 2 C. krusei (7.1% of isolates; MIC90, 8 microg/ml), 2 Rhodotorula spp. (4.6% of isolates, MIC90, 1 microg/ml), 8 Trichosporon spp. (33.3% of isolates; MIC90, 64 microg/ml), and 1 C. lipolytica (50% of isolates). Interestingly, most C. albicans (67 out of 77 isolates) resistant to 5FC were serotype B isolates.     

男性尿道炎和包皮龟头炎致病真菌的分布与药敏分析

目的了解男性念珠菌性尿道炎和包皮龟头炎的菌群分布及体外抗真菌药敏试验情况。方法菌株分离均来自复旦大学附属华山医院皮肤性病门诊临床症状轻重不一、真菌直接镜检阳性的61例患者。用科玛嘉念珠菌显色培养基及API 20C AUX鉴定系统进行菌种鉴定;采用CLSIM27-A2肉汤微量稀释法对61株临床分离念珠菌作了氟康唑、两性霉素B、氟胞嘧啶、伊曲康唑、伏立康唑、特比萘芬6种抗真菌药物敏感性测定。结果对培养阳性的61例菌株,通过科玛嘉念珠菌显色培养基及API 20C AUX鉴定系统作菌种鉴定,白念珠菌52例（85.2%）,近平滑念珠菌3例,光滑念珠菌2例,热带念珠菌2例,季也蒙念珠菌1例,克柔念珠菌1例。对52株白念珠菌的药敏试验显示氟康唑98.1%敏感,1.9%剂量依赖性敏感;氟胞嘧啶96.2%敏感,3.8%耐药;伊曲康唑44.2%敏感,40.5%剂量依赖性敏感,15.3%耐药;伏立康唑84.6%敏感,15.4%耐药;两性霉素B全部敏感;特比萘芬的MIC范围为1-64μg/ml,MIC50和MIC90皆为64μg/ml。结论在男性念珠菌性尿道炎和包皮龟头炎中,白念珠菌仍是第一位致病菌,体外药敏试验显示氟康唑、伏立康唑、氟胞嘧啶、两性霉素B对男性念珠菌性尿道炎均有较好的敏感性。     

Antifungal susceptibility profiles of <Emphasis Type="Italic">Coccidioides immitis</Emphasis> and <Emphasis Type="Italic">Coccidioides posadasii</Emphasis> from endemic and non-endemic areas

Coccidioidomycosis is a systemic fungal infection endemic in Southwestern United States, Mexico, Central and South America. The causal agents are Coccidioides immitis and C. posadasii. A large number of cases of coccidioidomycosis in New York State residents were identified. We compared susceptibility profiles of these isolates and of C. immitis isolates from California using mycelial phase inoculum and CLSI (NCCLS) M38–A broth microdilution protocol. Minimum fungicidal concentrations (MFC) were also determined. Results indicated that geometric mean MICs of amphotericin B (AMB, 0.06 μg/ml), fluconazole (FLC, 8.0 μg/ml), itraconazole (ITC, 0.07 μg/ml), ketoconazole (KTC, 0.04 μg/ml), voriconazole (VRC, 0.04 μg/ml), posaconazole (PSC, 0.17 μg/ml) and caspofungin (CSP, 0.15 μg/ml) were in susceptible range as per breakpoints published for pathogenic Candida species. However, geometric MFC for FLC was relatively higher (52.4 μg/ml). Also, no significant difference in MIC and MFC values was evident for C. immitis and C. posadasii isolates. In conclusion, current methods for antifungal susceptibility testing yield reproducible profiles for Coccidioides species, which appear to be highly susceptible to most antifungal agents.     

In vitro antifungal activity of anidulafungin

Anidulafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses. The antifungal spectrum of anidulafungin reaches the most common pathogenic fungi. Anidulafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the beta-1,3-D-glucan synthesis, an essential molecule for the cell wall architecture, with different consequences for Candida and Aspergillus, being anidulafungin fungicide for the former and fungistatic for the latter. This review describes the in vitro antifungal spectrum of anidulafungin based in the scientific and medical literature of recent years. We can underline that most than 99% of Candida isolates are susceptible to < or = 2 microg/ml of anidulafungin. MIC are very low (< or =0.125 microg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations < or = 2 microg/ml. An excellent activity of anidulafungin has been also described against Aspergillus, Pneumocystis and other fungi. However, its activity is very low against Cryptococcus and the Zygomycetes. The excellent activity of anidulafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.     

Atropurosides A-G, new steroidal saponins from Smilacina atropurpurea

Atropurosides A-G (1-7), seven new steroidal saponins, which possess new polyhydroxylated aglycones, were isolated from the rhizomes of Smilacina atropurpurea (Convallariaceae), together with a known saponin, dioscin (8). Their structures were elucidated on the basis of detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical methods. Antifungal testing of the eight compounds indicated that atropurosides B (2) and F (6) were fungicidal against Candida albicans, Candida glabrata, Cryptococcus neoformans, and Aspergillus fumigatus with minimum fungicidal concentrations (MFCs) < or = 20 microg/ml, while dioscin (8) was selectively active against C. albicans and C. glabrata (MFC < or = 5.0 microg/ml). Furthermore, the antifungal saponins 2, 6, and 8 were evaluated for their in vitro cytotoxicities in a panel of human cancer cell lines (SK-MEL, KB, BT-549, SK-OV-3, and HepG2) and non-cancerous Vero cells. All showed moderate cytotoxicities. It appears that the antifungal activity of these steroidal saponins correlates with their cytotoxicity against mammalian cells.     

Study of acute vulvovaginitis in sexually active adult women, with special reference to candidosis, in patients of the Francisco J. Muñiz Infectious Diseases Hospital

The results of microbiological vaginal secretions samples obtained from 749 women (from July 2001 to July 2002) were studied in the Bacteriology Unit of the Francisco Javier Mu?iz Hospital from Buenos Aires. All patients suffered acute vulvovaginitis were child bearing and sexually active women, 334 of them were HIV-positive. The following are the results of the microbiological studies: Lactobacillus spp 50.6%, Gardnerella vaginalis 25.6%, Candida spp 17.4%, Trichomonas vaginalis 5.3%, Neisseria gonorrhoeae 0.3% and B group Streptococcus 0.8%. Candida vaginitis was significantly more frequent in HIV-positive patients, (21.6% vs 14%; p = 0.0086); meanwhile, trichomoniasis was less common although the difference was not statistically significant (3.6 vs 6.7%, p = 0.0810). The following Candida species were isolated in this study: Candida albicans 76.8%, Candida glabrata 15.6%, Candida parapsilosis 2.9%, Candida tropicalis 1.5% and Candida krusei 0.7%. Eight cases (6.2%) of vaginitis were produced by two Candida species (C. albicans and C. glabrata), and in three cases (2.17%) Saccharomyces cerevisiae were isolated. Five women suffering acute vaginitis with Candida spp presented another etiologic agent of vaginal infection, three cases T. vaginalis and two cases G. vaginalis. The following are some of the most important findings of this study: 1) Half of the patients presented a normal microbial biota; 2) Candida spp vaginitis was significantly more frequent among HIV-positive women; 3) we observed a high incidence of Candida glabrata infections (15.9%), 4) 6.2% of vaginal candidiasis were caused by more than one Candida species and, 5) the susceptibility pattern of C. albicans and C. glabrata isolates against fluconazole was similar to the one observed in other studies. The majority of C. albicans isolates were susceptible to fluconazole (MIC90 = 0.5 microg/ml) meanwhile C. glabrata strains were much less susceptible to this drug (MIC50 and MIC90 = 32 microg/ml).     

Antifungal effects of hydrolysable tannins and related compounds on dermatophytes, mould fungi and yeasts

A series of hydrolysable tannins and related compounds was evaluated for antifungal activities against filamentous fungi (Epidermophyton floccosum; Microsporum canis; Microsporum gypseum; Trichophyton mentagrophytes; Trichophyton rubrum; Trichophyton tonsurans; Trichophyton terrestre; Penicillium italicum; Aspergillus fumigatus; Mucor racemosus; Rhizopus nigricans) and opportunistic yeasts (Candida albicans; Candida glabrata; Candidata krusei; Cryptococcus neoformans), using the agar dilution method. While all samples had no activity against the filamentous fungi in concentrations of 1.1-5.9 microM (1000 microg/ml), the phenolic compounds displayed significant potencies against all the opportunistic yeasts tested but C. albicans, with minimum inhibitory concentrations ranging from 0.02 to 0.1 microM (16-125 microg/ml). Although the presence of galloyl groups in flavonoids did not necessarily produce activity, this structural element, an HHDP moiety or its oxidatively modified entity proved to be an important structural feature of hydrolysable tannins. Comparison of dilution methods provided strong evidence of dependence of MIC values on the test method. Employing the microdilution broth method, the ellagitannin corilagin (MIC 0.8 nM) was found to be similarly potentially active as amphotericin B (MIC 0.5 nM) and sertaconazole (MIC 0.9 nM) against Candida glabrata strains. The order of effectiveness observed being 64- and 4-8-fold increased for corilagin and the reference compounds respectively, when compared with that of the agar dilution test.     

Mechanisms of resistance to antifungal agents: yeasts and filamentous fungi

Failure to respond to antifungal therapy could be due to in vitro resistance (intrinsic or developed during therapy) or clinical resistance; the latter is associated with numerous factors related to the host, the antifungal agent, or the infecting isolate. Recently, a susceptible MIC breakpoint ( < or =2 microg/ml) was designed for Candida spp. to all three available echinocandins, anidulafungin (Pfizer), caspofungin (Merck) and micafungin (Astellas) and treatment failures have been associated with MICs > 2 microg/ml. In some of these cases, clinical failure was associated with the genetic mutations described below. Azole and flucytosine breakpoints, and the echinocandin susceptible breakpoint, are useful when isolates are tested by CLSI standardized methods; breakpoints are also available by the EUCAST method. More recently, in vitro resistant MIC breakpoints have been assigned for filamentous fungi (moulds) vs. five antifungal agents, but these categories are not based on correlations of in vitro with in vivo response to therapy. However, itraconazole (Janssen), amphotericin B (Bristol-Myers) and voriconazole (Pfizer) clinical failures in aspergillosis have been correlated with MICs > 2 microg/ml. This article provides a review of reported resistance molecular mechanisms to antifungal agents since 2005; previous related reviews are also listed.     

CLSI M38-A2肉汤稀释法对蝙蝠蛾拟青霉(Paecilomyces hepiali)的药敏检测

[目的]对保健食品生产菌株蝙蝠蛾拟青霉(Paecilomyces hepiali)进行6种常见抗真菌药物:伊曲康唑、酮康唑、伏立康唑、环吡酮胺、5-氟胞嘧啶、氟康唑的药敏检测.[方法]参考美国国家临床实验室标准化委员会CLSI M38-A2《肉汤稀释法抗真菌药敏试验参考方案》.[结果]质控菌株MIC值均在参考范围之内,蝙蝠蛾拟青霉(P.hepiali)对以上6种药物的MIC值分别为1 mg/L、0.5 mg/L、0.25 mg/L、≥128 mg/L、64 mg/L、2 mg/L.[结论]M38-A2方案适合用来测定蝙蝠蛾拟青霉(P.hepiali)对抗真菌药物的敏感性,但获得菌株耐药敏感性的判别标准,仍需进一步的试验数据.     

In vitro susceptibilities of Candida spp. to Panomycocin, a novel exo-beta-1,3-glucanase isolated from Pichia anomala NCYC 434

Panomycocin, the killer toxin of Pichia anomala NCYC 434 (K5), is a 49 kDa monomeric glycoprotein with exo-beta-1,3-glucanase activity (patent pending). In this study we evaluated the in vitro activity of panomycocin against a panel of 109 human isolates of seven different pathogenic Candida spp. using microdilution and time-kill methods. Panomycocin was most active against C. tropicalis, C. pseudotropicalis and C. glabrata with MIC(90) values of 1 microg/ml. It displayed significant activity against C. albicans and C. parapsilosis with MIC(90) values of 4 and 2 microg/ml, respectively. For C. krusei, the MIC(90) value was 8 microg/ml. Panomycocin was fungicidal against all the tested Candida spp. The MFC values were only one or 2 dilutions higher than the MICs with the exception of C. krusei isolates with MFCs greater than or equal to 4xMIC. Results of this study indicated that panomycocin could be considered as a natural antifungal agent against Candida infections and has significant potential for further investigation.     

Antimicrobial susceptibility patterns of unusual nonfermentative gram-negative bacilli isolated from Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2002)

The antimicrobial susceptibility of 176 unusual non-fermentative gram-negative bacilli (NF-GNB) collected from Latin America region through the SENTRY Program between 1997 and 2002 was evaluated by broth microdilution according to the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. Nearly 74% of the NF-BGN belonged to the following genera/species: Burkholderia spp. (83), Achromobacter spp. (25), Ralstonia pickettii (16), Alcaligenes spp. (12), and Cryseobacterium spp. (12). Generally, trimethoprim/sulfamethoxazole (MIC50, < 0.5 microg/ml) was the most potent drug followed by levofloxacin (MIC50, 0.5 microg/ml), and gatifloxacin (MIC50, 1 microg/ml). The highest susceptibility rates were observed for levofloxacin (78.3%), gatifloxacin (75.6%), and meropenem (72.6%). Ceftazidime (MIC50, 4 microg/ml; 83.1% susceptible) was the most active beta-lactam against B. cepacia. Against Achromobacter spp. isolates, meropenem (MIC50, 0.25 microg/ml; 88% susceptible) was more active than imipenem (MIC50, 2 microg/ml). Cefepime (MIC50, 2 microg/ml; 81.3% susceptible), and imipenem (MIC50, 2 microg/ml; 81.3% susceptible) were more active than ceftazidime (MIC50, >16 microg/ml; 18.8% susceptible) and meropenem (MIC50, 8 microg/ml; 50% susceptible) against Ralstonia pickettii. Since selection of the most appropriate antimicrobial agents for testing and reporting has not been established by the NCCLS for many of NF-GNB species, results from large multicenter studies may help to guide the best empiric therapy.     

In Vitro Antifungal Susceptibility of Malassezia pachydermatis Strains Isolated from Dogs with Chronic and Acute Otitis Externa

Malassezia pachydermatis is a yeast that is frequently involved as a secondary/perpetuating factor in canine otitis externa. Topical therapies with different antifungal agents, mainly azole compounds, are generally successful in controlling the yeast overgrowth, but treatment failure and rapid recurrences are common. This study compared the in vitro antifungal susceptibility of M. pachydermatis isolates obtained from chronic and acute cases of otitis externa. The aim was to assess the possible onset of resistance mechanisms in isolates involved in long-lasting episodes with poor response to treatment. We evaluated the in vitro susceptibility to miconazole (MCZ) and clotrimazole (CTZ) of 42 isolates of M. pachydermatis obtained from dogs with chronic (group A, n = 25) and acute otitis (group B, n = 17), using a modified CLSI M27-A3 microdilution method. All isolates were inhibited by the antifungal agents employed, but Malassezia isolates from group A were significantly associated with higher minimum inhibitory concentration (MIC) values for both agents (Median MIC values: MCZ group A 2 µg/ml, group B 1 µg/ml; CTZ group A 8 µg/ml, group B 4 µg/ml). These findings prove that these isolates had a reduced in vitro susceptibility to the antifungal agents tested. However, it is unlikely that this could have any influence on the outcome of a topical treatment. Indeed, marketed products include concentrations of the tested agents that largely exceed even the highest MICs found in this study (in most cases at least 1,000 × the MIC, or greater). In conclusion, this study suggests that isolates of M. pachydermatis involved in chronic cases of canine external otitis and exposed to repeated antifungal treatments are unlikely to develop mechanisms of resistance of clinical relevance.     

Fluconazole susceptibility of Italian Candida dubliniensis clinical isolates determined by reference and simplified tests.

Candida dubliniensis ia an opportunistic pathogen mainly associated with oral candidiasis in human immunodeficiency virus (HIV)-infected individuals. We recently recovered the first Italian clinical isolates of C. dubliniensis from the oral cavities of seven HIV-seropositive subjects. The in vitro susceptibility to fluconazole (FLCZ) of these isolates was determined according to the National Committee for Clinical Laboratory Standards (NCCLS) M27-A broth microdilution method for yeasts. All seven isolates of C. dubliniensis were susceptible to FLCZ (MICs < or =0.5 microg/ml). Results of this reference method were compared to those obtained with simplified tests, more adapted to routine evaluation in hospital laboratories. Fungitest and Sensititre YeastOne colorimetric microplate-based methods have been evaluated. The agar disk diffusion method has also been tested on two different media: RPMI 1640-2% glucose and High Resolution-2% glucose-0.5 microg/ml methylene blue. All of the simplified methods tested were able to correctly identify FLCZ-susceptibility of this group of Italian C. dubliniensis isolates.     

Isavuconazole and Nine Comparator Antifungal Susceptibility Profiles for Common and Uncommon Candida Species Collected in 2012: Application of New CLSI Clinical Breakpoints and Epidemiological Cutoff Values

The in vitro activity of isavuconazole and nine antifungal comparator agents was assessed using reference broth microdilution methods against 1,421 common and uncommon species of Candida from a 2012 global survey. Isolates were identified using CHROMagar, biochemical methods and sequencing of ITS and/or 28S regions. Candida spp. were classified as either susceptible or resistant and as wild type (WT) or non-WT using CLSI clinical breakpoints or epidemiological cutoff values, respectively, for the antifungal agents. Isolates included 1,421 organisms from 21 different species of Candida. Among Candida spp., resistance to all 10 tested antifungal agents was low (0.0–7.9 %). The vast majority of each species of Candida, with the exception of Candida glabrata, Candida krusei, and Candida guilliermondii (modal MICs of 0.5 µg/ml), were inhibited by ≤0.12 µg/ml of isavuconazole (99.0 %; range 94.3 % [Candida tropicalis] to 100.0 % [Candida lusitaniae and Candida dubliniensis]). C. glabrata, C. krusei, and C. guilliermondii were largely inhibited by ≤1 µg/ml of isavuconazole (89.7, 96.9 and 92.8 %, respectively). Decreased susceptibility to isavuconazole was most prominent with C. glabrata where the modal MIC for isavuconazole was 0.5 µg/ml for those strains that were SDD to fluconazole or WT to voriconazole, and was 4 µg/ml for those that were either resistant or non-WT to fluconazole or voriconazole, respectively. In conclusion, these data document the activity of isavuconazole and generally the low resistance levels to the available antifungal agents in a large, contemporary (2012), global collection of molecularly characterized species of Candida.     

In vitro susceptibility of fungal and yeast clinical isolates to itraconazole and voriconazole

The interest on the in vitro susceptibility to itraconazole has recently increased due the availability of the intravenous formulation. In this study, comparative MICs of this antifungal with voriconazole were carried out in 62 clinical isolates of filamentous fungi and 100 yeasts isolates using the NCCLS microbroth methods described in M38-A and M27-A2 documents. A MIC90 of 0.125 micrograms per ml was observed for itraconazole and voriconazole against Aspergillus fumigatus. Higher susceptibility to itraconazole was found for the filamentous form of Sporotrhix schenckii (p = 0.001). Voriconazole was more effective against Scedosporium apiospermium while Scedosporium prolificans isolates were resistant to both azoles. Some isolates of Rhizopus stolonifer were susceptible to itraconazole and resistant to voriconazole, but without statistical significance. Susceptibility of nine species of Candida was similar for both triazoles used in this study. However, Candida glabrata was more susceptible to voriconazole. Some fluconazole-resistant Candida albicans isolates were susceptible to itraconazole and / or voriconazole. Cryptococcus neoformans was more susceptible to itraconazole than to voriconazole. Itraconazole and voriconazole showed very close in vitro activity against the tested fungal isolated, except against S. schenckii. In spite of this, there were some differences in susceptibility among isolates within the same fungal species.     

Characterization of the in vitro antimycotic activity of a novel killer protein from Williopsis saturnus DBVPG 4561 against emerging pathogenic yeasts

A novel killer toxin, labelled as KT4561, secreted by Williopsis saturnus DBVPG 4561, was found to possess a wide antimycotic activity against strains of Candida glabrata, Issatchenkia orientalis and Pichia guillermondii. KT4561 was precipitated by ethanol and purified by ion-exchange chromatography. The active protein migrated as a single band in SDS-PAGE and was characterized by a molecular weight of approximately 62 kDa. Purified KT4561 was active across wide ranges of temperature (5-45 degrees C) and pH (4.5-8.0) and displayed a rapid decrease in viability of yeast cells after 4-8 h. The in vitro activity of KT4561 against 102 yeast isolates (79% of clinical origin) was determined: MIC(50) and MIC(90) of strains were 0.08 and 0.15 microg/ml for C. glabrata, 0.03 and 0.23 microg/ml for I. orientalis and 1.50 and 2.25 microg/ml for P. guilliermondii. Comparative susceptibility tests showed that a high number of strains used in the present study were insensitive to selected azole and polyene antibiotics. The present study demonstrated the potential of KT4561 to be applied as novel control agent against pathogenic yeasts.     

Metabolites from the endophytic fungus Xylaria sp. PSU-D14

Glucoside derivatives, xylarosides A (1) and B (2), were isolated from the broth extract of the endophytic fungus Xylaria sp. PSU-D14 along with two known compounds, sordaricin (3) and 2,3-dihydro-5-hydroxy-2-methyl-4H-1-benzopyran-4-one (4). The structures were assigned by spectroscopic methods. Sordaricin (3), one of the known metabolites, exhibited moderate antifungal activity against Candida albicans ATCC90028 with a MIC value of 32 microg/ml.