In vitro antifungal activity of a novel lipopeptide antifungal agent, FK463, against various fungal pathogens

The antifungal activities of FK463 against various pathogenic fungi were tested by standard broth microdilution methods, and compared with the activities of five currently available antifungal agents; viz., fluconazole (FLCZ), itraconazole, miconazole, amphotericin B and flucytosine. Fourteen clinical isolates of Candida albicans categorized as FLCZ susceptible, FLCZ susceptible-dose dependent and FLCZ resistant were similarly susceptible to FK463 with geometric (GM) MIC values of 0.010, 0.011 and 0.015 microg/ml, respectively. All of 17 clinical isolates of Aspergillus fumigatus were inhibited by FK463 at 0.0078 microg/ml or lower concentrations. The antifungal activity of FK463 against a wider range of medically important yeasts and filamentous fungi were studied using stock fungal strains. While Cryptococcus, Trichosporon, Fusarium, Pseudallescheria and Alternaria species or zygomycetes were scarcely or not inhibited by 16 microg/ml of FK463, two Candida species (C. albicans, C. glabrata), as well as all species of Aspergillus, Paecilomyces and Penicillium, were highly susceptible with GM-MICs of < or = 0.008 microg/ml. The other fungal species including several non-albicans Candida were less susceptible with GM-MICs ranging between 0.016 and 2 microg/ml. MICs of the reference drugs were within the range thus previously reported. These results suggest that FK463 be of use in the treatment of serious fungal infections.     

In vitro antifungal activity of amorolfine against Malassezia species

In vitro antifungal activities of a new morpholine agent, amorolfine (MT-861) were investigated, against 39 strains of Malassezia furfur (11 stock cultures and 28 clinical isolates) and 8 strains (stock cultures) of Malassezia pachydermatis, in comparison with those of 2 reference drugs, clotrimazole (CTZ) and bifonazole (BFZ). Of the 3 antifungal agents, MT-861 exhibited strongest antifungal activities against the stock cultures of M. furfur and M. pachydermatis with average MIC values of 0.428 and 0.174 micrograms/ml, respectively; and the average BFZ activity was less than 1/10, and the average CTZ activity was 1/100, of the average MT-861 activity. All of the clinical isolates of M. furfur also showed high susceptibilities, though they were more susceptible to BFZ and CTZ.     

ε-聚赖氨酸对白念珠菌抑菌活性及机制研究

目的 研究ε-多聚赖氨酸(ε-poly-L-lysine, ε-PL)对白念珠菌(Candida albicans)的抑菌活性及抑菌机制。方法 以白念珠菌的标准菌株ATCC64548(氟康唑敏感株)、ATCC64550(氟康唑耐药株)以及临床收集的50株菌为实验菌株,按照CLISI- M27文件中的微量稀释法测定ε-多聚赖氨酸的MIC、MFC和SMIC50值;绘制48h内的浮游菌株时间-生长曲线和生物膜抑制-时间曲线;连续观测并记录4h内的芽管形成率和芽管长度;测定药物处理前后白念珠菌的丙二醛和活性氧(ROS)含量。结果 ε-PL对白念珠的最低抑菌浓度(MIC)为512μg/mL,最低杀菌浓度(MFC)为1024μg/mL,SMIC50为512μg/mL,ε-PL对白念珠菌浮游菌及生物膜的抑菌作用随着浓度的升高作用愈明显。抑菌-时间曲线结果表明ε-PL对白念珠菌的浮游菌和生物膜在12h左右即产生明显抑制作用。芽管实验的结果表明高浓度的ε-PL对白念珠菌的芽管形成率及芽管长度具有明显抑制作用。ε-PL作用于白念珠菌后MDA和ROS含量呈现上升趋势,并且与药物浓度大小成正相关。结论 ε-PL对白念珠菌浮游菌株及生物膜均有良好的抑制作用,高浓度ε-PL对白念珠菌主要毒力菌丝有明显抑制作用,ε-PL作用导致白念珠菌内产生大量的活性氧(ROS)以及产生一定程度的脂质氧化,提示ε-PL可能通过氧化作用发挥抑菌效果。     

头孢吡肟的体外抗菌活性

目的了解头孢吡肟对临床常见病原菌的体外抗菌活性。方法采用Kirby-Bauer琼脂扩散法对213株临床分离菌进行头孢吡肟等6种常用抗生素的药物敏感试验,采用E-test法测定头孢吡肟等6种常用抗生素对其中172株细菌的最低抑菌浓度(MIC)。结果头孢吡肟对革兰阴性菌(包括肠杆菌属等)的抗菌活性高于亚胺培南、阿米卡星、头孢噻肟钠和左氧氟沙星,与头孢哌酮/舒巴坦相仿。头孢吡肟对革兰阳性菌的抗菌活性高于头孢噻肟钠,与头孢哌酮/舒巴坦、亚胺培南相似。结论头孢吡肟对临床常见致病菌有较好的抗菌活性,当病原菌及药物敏感试验结果不明时,可作为院内感染菌的经验性用药。     

布替萘芬体外抗真菌活性及对真菌麦角甾醇合成的影响

目的研究抗真菌药物布替萘芬的体外抗真菌活性和对真菌麦角甾醇生物合成的影响。方法以氟康唑和酮康唑为对照,分别用微量液基稀释法和薄层色谱扫描法研究布替萘芬的体外抗真菌活性和对真菌麦角甾醇生物合成的影响。结果布替萘芬对念珠菌属的MIC大于16μg/ml,对新生隐球菌的MIC为1～8μg/ml,对浅部真菌的MIC小于4μg/ml。布替萘芬能使真菌中麦角甾醇的合成减少,而增加角鲨烯的含量,其含量变化与布替萘芬均呈剂量依赖性。结论布替萘芬的体外抗真菌活性优于氟康唑,与酮康唑作用相当,其对部分浅部真菌的抗菌活性优于酮康唑。布替萘芬为角鲨烯环氧化酶抑制剂,其作用靶酶与氮唑类抗真菌药不同,用薄层色谱扫描法能考察其对角鲨烯环氧化酶的抑制活性。     

In vitro evaluation on inhibitory nature of some Neem formulations against plant pathogenic fungi

Different Neem formulations derived from the Neem tree (Azadirachta indica) have been found to be potential fungicides against a broad spectrum of plant pathogenic fungi. Some Neem formulations viz. Achook (0.15% EC), Bioneem (0.03% EC), Nimbecidine (0.03% EC) and Neemark (0.03% EC) were examined against some plant pathogenic fungi such as (Fusarium oxysporum, Alternaria solani, Curvularia lunata, Helminthosporium sp. and Sclerotium rolfsii). Among these Achook (0.15% EC) was found to be more active in terms of Minimum Inhibition Concentration (MIC) value followed by Bioneem, Neemark and Nimbecidine. Remarkably, although all these formulations are oil based, Neem oil itself did not exhibit any fungicidal activity.     

酮康唑微囊对部分真菌的抑菌实验

目的　考察临床分离的几种致病真菌对酮康唑微囊的体外敏感性。方法　采用试管稀释法和琼脂稀释法进行体外药效学研究。结果　 2 1株念珠菌对酮康唑、酮康唑微囊、氟康唑片的MIC分别为 0 .0 2～ 2 .5、6 .2 5～ 10 0、0 .319～ 10 0 μg·ml-1;1株酵母菌对这 3种药物的MIC分别为 0 .0 8～ 0 .16、12 .5～ 2 5、2 5 μg·ml-1结论　酮康唑微囊具有一定的体外抗真菌活性。     

In vitro antifungal activity of naphthoquinone derivatives

In vitro antifungal activities of naphtoquinone-derivatives, which are constituents of Shikon, roots of Lithospermum erythrorhizon, were investigated against several fungal pathogens. When the biological activity of these compounds was tested against fungi, a wide range of sensitivity was recorded. Shikonin was found to have a stronger than fluconazole against yeast-like fungi: four-fold against Candida krusei (minimal inhibitory concentration (MIC); 4 microg/ml) and two-fold (MIC; 4 microg/ml) against Saccharomyces cerevisiae, though it showed the same potency as fluconazole against C. glabrata. Deoxyshikonin also exhibited four-fold stronger activity against C. krusei (MIC; 4 microg/mi) and three-fold (MIC; 2 microg/ml) stronger against S. cerevisiae. Acetylshikonin and beta-hydroxyisovaleryl shikonin showed lower activities against all fungal pathogens except for C. krusei compared with the standard. Against the filamentous fungus, Trichosporon cutaneum, all naphthoquinones were found to have a range of activity with lower potency than standard. This result provides a rational basis for the clinical use of shikon and shows the possibility of its use in medicinal treatment as an anti-inflammatory agent with antifungal activity.     

In vitro activity of novel imidazole antifungal agent NND-502 against Malassezia species

The in vitro activity of NND-502, a novel antifungal imidazole compound, was tested against the three major Malassezia species by an agar dilution method with modified Dixon medium and compared with the activities of three reference antifungal drugs of topical use, lanoconazole (LCZ), bifonazole (BFZ) and terbinafine (TBF). The geometric mean (GM)-MICs of NND-502 for 25 strains of M. furfur, 15 strains of M. sympodialis and ten strains of M. slooffiae were approximately 1.4, 0.1 and 1.0 mg/l, respectively, showing the greatest activity against M. sympodialis and the least against M. slooffiae. These values were similar to that of LCZ, but four to 69 times lower than that of BFZ and two to three times lower than that of TBF. The results suggest that NND-502 might be beneficial in the treatment of Malassezia-associated skin diseases.     

In vitro activity of taurolidine, chlorophenol-camphor-menthol and chlorhexidine against oral pathogenic microorganisms.

The antimicrobial activity of taurolidine (Taurolin, CAS 19388-87-5), a synthetic broad-spectrum antimicrobial agent and anti-toxin, and two conventional antiseptics, chlorophenol-camphor-menthol (CCM) and chlorhexidine digluconate (CHX) were compared using the serial dilution test on 10 potential oral pathogenic bacterial species. The minimum inhibitory and minimum bactericidal concentrations were lowest for CHX (MIC 0.03-0.12 mg/ml), followed by taurolidine (MIC 0.12-0.5 mg/ml) and CCM (MIC 0.5-2.0 mg/ml). However, if both bacterial efficacy and cytotoxicity are considered, only taurolidine achieves extensive bactericidal activity with tissue tolerability.     

In vitro evaluation of sulfadrugs against fungi causing otomycosis

The efficacy of four sulfadrugs i.e., sulfadiazine, sulfamethoxazole, sulfaguanidine and sulfamoxole were taken in different doses (500, 1000, 1500, 2000 and 2500 ppm) to test their effectiveness against five pathogenic organisms for the control of mycelial growth and sporulation. Amongst the drugs tested sulfamethoxazole seems to be most effective against most of the test fungi showing 96.78, 90.53, 86.62, 54.16 and 43.91 percent inhibition in mycelial growth of P. nigricans, A. flavus, A. corymbifera, A. niger and C. albicans, respectively at its 2500 ppm dose in the basal medium. Gradual reduction in sporulation in all the test organisms almost in all the sulfadrugs have caused inhibition in sporulation, in comparison to their respective controls. Maximum inhibitory effect of sulfadiazine was recorded in A. niger showing 77.26 percent inhibition in the mycelial growth at a dose of 2500 ppm. Sulfaguanidine at its higher dose i.e., 2500 ppm proved to be most toxic against A. corymbifera causing 56.39 percent inhibition in the mycelial growth, while the same dose could not be found much effective against other test fungi. Sulfamoxole was found to be quite effective against most of the test fungi causing 47.16 to 85.86 percent inhibition in the mycelial growth. A gradual inhibition in the vegetative growth and sporulation or budding in all the test fungi was noted by increasing the concentrations of the test sulfadrugs.     

In vitro activity of protoanemonin, an antifungal agent

Protoanemonin, the lactone of gamma-hydroxy-vinylacrylic acid, isolated from Pulsatilla alpina has in vitro activity against fungi. The MIC is 15 micrograms/ml and RNA inhibition seems to be the first target of the drug. The LD50 of protoanemonin in male Swiss albino mice was 190 mg/kg.     

In vivo and in vitro antifungal activity of fluconazole

We examined in vivo efficacy and in vitro activity of fluconazole, a novel triazole antifungal agent, and obtained results which are summarized as follows: 1. Fluconazole showed a higher serum concentration than ketoconazole after oral administration to mice. The 50% effective dose of fluconazole administered orally to mice was similar to that of fluconazole injected to mice intraperitoneally in a systemic candidiasis model. 2. Prophylactic effects of fluconazole were excellent against systemic candidiasis, cryptococcosis and aspergillosis in mice in comparison with those of ketoconazole and miconazole. 3. The multiple administration of fluconazole effectively decreased the number of viable cells of Candida albicans colonized in kidneys of mice when the serum level of fluconazole was kept to exceed its IC99 values against the inoculated pathogen. Thus, a good correlation between the in vitro activity of fluconazole and its in vivo efficacy was confirmed. In vivo efficacies of ketoconazole and miconazole, however, failed to reflect their marked in vitro activities. 4. C. albicans No. 32 developed no drug-resistance to fluconazole during transfers in medium containing fluonazole at a concentration of 1 micrograms/ml.     

In vitro antifungal activity of itraconazole, a new triazole antifungal agent, against clinical isolates from patients with dermatomycoses]

In vitro antifungal activities of itraconazole (ITZ), a triazole antifungal agent, against clinical isolates obtained from patients with superficial and subcutaneous mycoses were examined using the agar dilution method on casitone agar. The clinical isolates tested were 7 species and 263 isolates including Trichophyton mentagrophytes (104 isolates), Trichophyton rubrum (103 isolates), Microsporum canis (3 isolates), Epidermophyton floccosum (2 isolates), Candida albicans (32 isolates), Malassezia furfur (7 isolates) and Sporothrix schenckii (12 isolates). The results are summarized as follows: 1. MIC values of ITZ for the isolates of dermatophytes and M. furfur distributed in a range of less than 0.0012-5 micrograms/ml indicating that ITZ had greater in vitro activities. These in vitro activities of ITZ were greater than those of clotrimazole or bifonazole. 2. C. albicans isolates were divided into 2 groups in terms of ITZ-susceptibilities, a high susceptibility group and low-susceptibility group with MIC values of 0.02-0.08 micrograms/ml and greater than 10 micrograms/ml, respectively. 3. The in vitro activities of ITZ against S. schenckii isolates with a geometric mean MIC of 0.119 micrograms/ml were greater than those of ketoconazole, miconazole or amphotericin B used as reference drugs.     

Ciclopiroxolamine: in vitro antifungal activity against clinical yeast isolates

The in vitro susceptibility of 225 clinical isolates of yeasts to ciclopiroxolamine (CPO) was compared with that of clotrimazole, econazole, ketoconazole, miconazole, tioconazole, fluconazole, itraconazole and nystatin using a standardized agar diffusion method (NeoSensitabs). Two hundred and eight strains of yeasts comprising 16 species of Candida and 22 strains belonging to other yeast genera were tested. One strain (0.4%) was resistant, four strains (1.8%) of intermediate susceptibility and 220 strains (97.3%) susceptible to CPO. More strains were susceptible to CPO than to the other antifungals studied. Susceptibility patterns of antifungal agents were not linked to species. The in vitro antifungal susceptibility profile of CPO was better than topical azole derivatives or fluconazole and itraconazole against a wide variety of clinically important yeasts.