• Title/Summary/Keyword: antifungal resistance

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Candida non albicans with a High Amphotericin B Resistance Pattern Causing Candidemia among Cancer Patients

  • Kalantar, Enayatollah;Assadi, Mojan;Pormazaheri, Helen;Hatami, Shiva;Barari, Maryam Agha;Asgari, Esfandiar;Mahmoudi, Elaheh;Kabir, Kourosh;Marashi, Seyed Mahmoud Amin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10933-10935
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    • 2015
  • Background: Many scientists have reported Candida species to be of great concern because of the high frequency that they colonize and infect human hosts, particularly cancer patients. Moreover, in the last decades Candida species have developed resistance to many antifungal agents. Based on this, we aimed to identify and determine the prevalence of Candida spp from blood culture bottles among cancer patients and their antifungal resistance pattern. Materials and Methods: From the blood culture bottles isolation and identification of the Candida spp were performed by conventional microbiological techniques. The in vitro antibiotic resistance pattern of the isolates was determined by CLSI guidelines. Genomic DNA was isolated and amplified. Each gene was separated by agar gel electrophoresis. Results: Identification of Candida spp was based on the presence of yeast cells in direct examination, culture and DNA extraction. Of the 68 blood samples collected during the study period (April 2013 to October 2013), five (7.35%) were positive for the presence of Candida spp, 2 (40%) of which were identified as Candida albicans and 3 (60%) were Candida non-albicans. Conclusions: High resistance to amphotricin B was observed among all the Candida non-albicans isolates. Regular investigations into antifungal resistance will help us to get an updated knowledge about their antibiotic resistance pattern which may help the physician in selecting the antibiotics for empirical therapy.

항진균성 항생물질을 생산하는 streptoverticillium sp. NA-4803의 분리 및 동정

  • Lim, Dae-Seog;Yoon, Sang-Kun;Lee, Myung-Sub;Yoon, Won-Ho;Kim, Chang-Han
    • Microbiology and Biotechnology Letters
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    • v.24 no.6
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    • pp.664-670
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    • 1996
  • The aim of the present research program was to develop a strain of actinomycetes producing antifungal substance. Soil samples were collected from various sites in Korea and a number of actinomycetes were isolated from the soil samples by applying selective agar for actinomycetes. Among over 440 isolates, a strain (NA-4803) producing antifungal substance against Trichophyton spp. Nannizzia otae and Pyricularia oryzae was selected. The strain NA-4803 was identified as strain similar to Streptoverticillium blastmyceticum with respect to morphological and physiological characteristics, lecithinase and lipolytic activity, degradation of organic compounds, resistance to antibiotics and utilization of carbon and nitrogen sources. But it showed some differences such as positive reaction of nitrate reduction, negative reaction of L-tyrosine degradation, resistance to cephaloridine, and utilization of I -rhamnose and inulin. The strain NA-4803 was named as Streptoverticillium sp. NA-4803.

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In Vitro Antifungal Activities of Amphotericin B, Fluconazole, Itraconazole, Terbinafine, Caspofungin, Voriconazole, and Posaconazole against 30 Clinical Isolates of Cryptococcus neoformans var. neoformancs

  • Lee, Young-Ki;Fothergill, Annette W.
    • Mycobiology
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    • v.31 no.2
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    • pp.95-98
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    • 2003
  • Aantifungal agents were tested against 30 clinical isolates of Cryptococcus neoformans var. neoformans using the NCCLS method(M27-A2). Posaconazole, itraconazole and amphotericin B had lower MIC than the remaining four antifungal agents. The MIC result for posaconazole was over 220-fold lower active than fluconazole. Fluconazole MICs for most isolates fell within the dose-dependant range. The overall MIC ranges and $MIC_{50}s$ were amphotericin B(0.03-0.25; 0.25), fluconazole(0.5-64; 16), itraconazole(0.015-1; 0.125), terbinafine(0.06->2; 1), caspofungin(8-32; 32), voriconazole(0.015-0.5; 0.25), and posaconazole(0.015-0.25; 0.06 ${\mu}g/ml$), respectively. In conclusion, the $MIC_{50}s$ of these drugs did not exhibit any sign of an upward shift with the exception of fluconazole and tendency cross-resistance between the seven drugs was not observed. We conclude that in vitro resistance to antifungal agents has not significantly changed despite the recent wide-spread use of triazoles for long-term treatment of Cryptococcal meningitis.

Novel Approaches for Efficient Antifungal Drug Action

  • Lee, Heejeong;Lee, Dong Gun
    • Journal of Microbiology and Biotechnology
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    • v.28 no.11
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    • pp.1771-1781
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    • 2018
  • The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

Purification and Identification of a Novel Antifungal Protein Secreted by Penicillium citrinum from the Southwest Indian Ocean

  • Wen, Chao;Guo, Wenbin;Chen, Xinhua
    • Journal of Microbiology and Biotechnology
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    • v.24 no.10
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    • pp.1337-1345
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    • 2014
  • A novel antifungal protein produced by the fungal strain Penicillium citrinum W1, which was isolated from a Southwest Indian Ocean sediment sample, was purified and characterized. The culture supernatant of P. citrinum W1 inhibited the mycelial growth of some plant pathogenic fungi. After saturation of P. citrinum W1 culture supernatants with ammonium sulfate and ion-exchange chromatography, an antifungal protein (PcPAF) was purified. The N-terminal amino acid sequence analysis showed that PcPAF might be an unknown antifungal protein. PcPAF displayed antifungal activity against Trichoderma viride, Fusarium oxysporum, Paecilomyces variotii, and Alternaria longipes at minimum inhibitory concentrations of 1.52, 6.08, 3.04, and $6.08{\mu}g/disc$, respectively. PcPAF possessed high thermostability and had a certain extent of protease and metal ion resistance. The results suggested that PcPAF may represent a novel antifungal protein with potential application in controlling plant pathogenic fungal infection.

Antifungal Effect of Tanshinone from Salvia miltiorrhiza against Disseminated Candidiasis (Tanshinone 단삼성분의 전신성 캔디다증에 대한 항균효과)

  • Han, Yongmoon;Joo, Inkyung
    • YAKHAK HOEJI
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    • v.57 no.2
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    • pp.119-124
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    • 2013
  • The aim of this present study was to investigate the antifungal effect of tanshinones isolated from Salvia miltiorrhiza against Candida ablicans, a polymorphic fungus. For the work, tanshinone IIA (TSN), cryptotanshinone (CTS), and dihydrotanshinone I (DTS) were chosen. Initially, their antifungal effect was analyzed by in-vitro susceptibility test. Data from the susceptibility test showed that while all of these three compounds had antifungal activity, DTS was the most potent. At $100{\mu}g$ DTS/ml, there was about 80% CFU (colony forming unit) reduction as compared to DTS-untreated C. albicans yeast cells (P<0.05). Thus, DTS was selected to determine its antifungal activity in a murine model of disseminated candidiasis due to C. albicans. Results showed that DTS enhanced resistance of mice against disseminated candidiasis. During the entire period of 30-day observation, 60% of DTS-given mice groups survived whereas control animals all died within 14 days (P<0.05). Moreover, DTS inhibited the hyphal production, one of the virulence factors of this fungus, from the blastoconidial form of the fungus. Therefore, the tanshinone appears to have antifungal activity specific for C. albicans infection, which could possibly be mediated by the blockage of hyphal production.

Genomic Tandem Quadruplication is Associated with Ketoconazole Resistance in Malassezia pachydermatis

  • Kim, Minchul;Cho, Yong-Joon;Park, Minji;Choi, Yoojeong;Hwang, Sun Young;Jung, Won Hee
    • Journal of Microbiology and Biotechnology
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    • v.28 no.11
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    • pp.1937-1945
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    • 2018
  • Malassezia pachydermatis is a commensal yeast found on the skin of dogs. However, M. pachydermatis is also considered an opportunistic pathogen and is associated with various canine skin diseases including otitis externa and atopic dermatitis, which usually require treatment using an azole antifungal drug, such as ketoconazole. In this study, we isolated a ketoconazole-resistant strain of M. pachydermatis, designated "KCTC 27587," from the external ear canal of a dog with otitis externa and analyzed its resistance mechanism. To understand the mechanism underlying ketoconazole resistance of the clinical isolate M. pachydermatis KCTC 27587, the whole genome of the yeast was sequenced using the PacBio platform and was compared with M. pachydermatis type strain CBS 1879. We found that a ~84-kb region in chromosome 4 of M. pachydermatis KCTC 27587 was tandemly quadruplicated. The quadruplicated region contains 52 protein coding genes, including the homologs of ERG4 and ERG11, whose overexpression is known to be associated with azole resistance. Our data suggest that the quadruplication of the ~84-kb region may be the cause of the ketoconazole resistance in M. pachydermatis KCTC 27587.

Synergistic Antifungal Activity against Disseminated Candidiasis by Combination Therapy of Crataegi Fructus Extract and Fluconazole (전신성 캔디다증에 대한 산사자 추출물과 Fluconazole의 병용요법에 의한 항진균 상승효과)

  • Han, Yongmoon
    • YAKHAK HOEJI
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    • v.59 no.6
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    • pp.259-265
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    • 2015
  • In recent, there are increasing reports about pharmacological activities of Crataegi Fructus which has been used for many centuries as medicinal and food sources in East Asia. However, its antifungal efficacy needs to be investigated. Thus, in the current study, we determined synergistic antifungal activity of the Crataegi Fructus extract (CFE) when combined with fluconazole (FLC) against disseminated candidiasis due to Candida albicans. This fungus is one of the most problematic fungal pathogens. Data resulting from a microdilution susceptibility test showed that CFE had a dose-dependent antifungal activity. When the extract was combined with FLC, the activity was synergistic. For example, the antifungal activity by the combination of CFE at $20{\mu}g/ml$ plus FLC at $0.1{\mu}g/ml$ was 4 times more effective than antifungal activity by FLC alone at the same concentration (P<0.05). In the murine model of disseminated candidiasis, the combination therapy potentiated resistance of mice, resulting in 80% of C. albicans-infected animals surviving the entire period of 40 days observation, whereas mice given CFE alone or FLC alone all died with 17 and 23 days, respectively, although they survived longer than the untreated control animals (P<0.05). The CFE's antifungal activity seemed to be related to the blockage of hyphal production of C. albicans yeast cells. In summary, CFE has a synergistic antifungal activity, which can be produced by combining CFE with FLC. Thus, our data strongly indicate that CFE may be a potential candidate as an antifungal agent for combination therapy.

Antifungal Synergy of Theaflavin and Epicatechin Combinations Against Candida albicans

  • Betts, Jonathan W.;Wareham, David W.;Haswell, Stephen J.;Kelly, Stephen M.
    • Journal of Microbiology and Biotechnology
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    • v.23 no.9
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    • pp.1322-1326
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    • 2013
  • New antifungal agents are required to compensate for the increase in resistance to standard antifungal agents of Candida albicans, which is an important opportunistic fungal pathogen that causes minor infections in many individuals but very serious infections in those who are immune-compromised. In this study, combinations of theaflavin and epicatechin are investigated as potential antifungal agents and also to establish whether antifungal synergy exists between these two readily accessible and cost-effective polyphenols isolated from black and green tea. The results of disc diffusion assays showed stronger antibacterial activity of theaflavin:epicatechin combinations against C. albicans NCTC 3255 and NCTC 3179, than that of theaflavin alone. Minimum inhibitory concentrations (MICs) of 1,024 ${\mu}g/ml$ with theaflavin and 128-256 ${\mu}g/ml$ with theaflavin:epicatechin combinations were found. The fractional inhibitory concentration indexes were calculated, and the synergy between theaflavin and epicatechin against both isolates of C. albicans was confirmed. Theaflavin:epicatechin combinations show real potential for future use as a treatment for infections caused by C. albicans.

Antifungal Activity of Glycycoumarin to Candida albicans (Glycycoumarin 감초성분의 항진균효과)

  • Lee, Jue-Hee;Lee, Young-Mi;Han, Yong-Moon
    • YAKHAK HOEJI
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    • v.55 no.3
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    • pp.234-239
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    • 2011
  • Glycycoumarin, a 3-arylcoumarine isolated from Glycyrrhizae radix (a family of Leguminosae), is reported to have anti-bacterial activity. However, its antifungal activity is still unknown. In this present study, the antifungal activity of glycycoumarin (GLM) against Candida albicans, a polymorphic fungus was investigated. Possible mechanism such as blocking of the hyphal induction was also analyzed. By the in-vitro susceptibility analysis, GLM showed anticandidal activity, resulting in an almost complete inhibition of the fungal growth at a concentration of 320 ${\mu}g/ml$, which was equivalent to the efficacy of fluconazole at the same dose. In the murine model of disseminated candidiasis GLM enhanced resistance of mice against the disseminated disease (P<0.05), resulting in 60% protection of GLM-treated mice group during a period of 21-day observation. As for its mechanism of the antifungal activity, GLM blocked hyphal production, one of the important of virulence factors by the fungus, from the yeast form of C. albicans (P<0.01). These data indicate that GLM may contribute to the perspectives that focus on the development of a novel agent with antifungal activity specific for C. albicans infection.