In vitro and in vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gattii: an emerging fungal pathogen.
Objectives: T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against the majority of fungal pathogens. In this study, the antifungal activity of T-2307 against Cryptococcus gattii was evaluated in comparison with those of amphotericin B, fluconazole and voriconazole in vitro an...
| Publicado en: | Journal of Antimicrobial Chemotherapy (JAC) Vol. 72; no. 6; pp. 1709 - 1714 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Jun2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=123183629&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 123183629 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03057453 N5O jtl: Journal of Antimicrobial Chemotherapy (JAC) issn: 03057453 maglogo: N pubinfo: dt: Jun2017 vid: 72 iid: 6 pid: 622 pub: Oxford University Press / USA artinfo: ui: 123183629 123183629 NLM28201509 123183629 10.1093/jac/dkx020 NLM28201509 123183629 ppf: 1709 ppct: 5 formats: tig: atl: In vitro and in vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gattii: an emerging fungal pathogen. aug: au: Hiroshi Nishikawa Yoshiko Fukuda Junichi Mitsuyama Masato Tashiro Akitaka Tanaka Takahiro Takazono Tomomi Saijo Kazuko Yamamoto Shigeki Nakamura Yoshifumi Imamura Taiga Miyazaki Hiroshi Kakeya Yoshihiro Yamamoto Katsunori Yanagihara Hiroshi Mukae Shigeru Kohno Koichi Izumikawa Nishikawa, Hiroshi Fukuda, Yoshiko Mitsuyama, Junichi affil: Research Laboratories, Toyama Chemical Co., Ltd, 2-4-1 Shimookui, Toyama, Japan sug: subj: Antifungal Agents Pharmacodynamics Cryptococcus Drug Effects Organic Chemicals Administration and Dosage Cryptococcosis Drug Therapy Organic Chemicals Pharmacodynamics Antifungal Agents Therapeutic Use Lung Diseases, Fungal Microbiology Amphotericin B Administration and Dosage Amphotericin B Pharmacodynamics Animal Studies Mice Organic Chemicals Adverse Effects Lung Microbiology Models, Biological Brain Microbiology Voriconazole Pharmacodynamics Cryptococcus Organic Chemicals Therapeutic Use Antifungal Agents Administration and Dosage Fluconazole Therapeutic Use Amphotericin B Adverse Effects Drug Resistance, Microbial Amphotericin B Therapeutic Use Drug Discovery Antifungal Agents Adverse Effects Fluconazole Pharmacodynamics Microbial Culture and Sensitivity Tests Voriconazole Therapeutic Use Cryptococcosis Microbiology Lung Diseases, Fungal Drug Therapy ab: Objectives: T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against the majority of fungal pathogens. In this study, the antifungal activity of T-2307 against Cryptococcus gattii was evaluated in comparison with those of amphotericin B, fluconazole and voriconazole in vitro and in vivo .Methods: The MICs for 15 clinical isolates were determined according to CLSI guidelines and time-kill studies were performed using C. gattii YF2784. In a murine model for intranasal pulmonary infection caused by C. gattii YF2784, the test compounds were administered once daily for 7 days from 2 h or 14 days post-infection. The viable counts in the lungs and brain were determined at 21 days post-infection.Results: The MIC range, MIC 50 , MIC 90 and geometric mean MIC of T-2307 were 0.0078-0.0625, 0.0313, 0.0625 and 0.0394 mg/L, respectively. The MIC of T-2307 was significantly lower than those of fluconazole, voriconazole and amphotericin B. T-2307 showed concentration-dependent fungicidal activity at 4 times the MIC or higher. Administration of T-2307 at 2 mg/kg/day, amphotericin B at 1 mg/kg/day and fluconazole at 160 mg/kg/day from 2 h post-infection significantly reduced viable counts in the lungs and brain. However, when the administration was started 14 days post-infection, only T-2307 significantly reduced the viable counts in both the lungs and the brain at 1 mg/kg/day.Conclusions: T-2307 shows excellent in vitro and in vivo antifungal activities against C. gattii and would be a promising new candidate for the treatment of cryptococcosis. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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