ici-195739 and Candidiasis

ici-195739 has been researched along with Candidiasis* in 8 studies

Trials

1 trial(s) available for ici-195739 and Candidiasis

ArticleYear
A dose comparison study of a new triazole antifungal (D0870) in HIV-positive patients with oral candidiasis.
    AIDS (London, England), 1997, Volume: 11, Issue:6

    This multicentre study evaluated the clinical efficacy and tolerability of D0870 in treating oropharyngeal candidiasis in HIV-positive patients who had no history of clinical resistance to fluconazole.. Three regimens were evaluated in two phases. In phase I a 50 mg initial dose was followed by 10 mg for 4 days (Group 1). In phase II a 100 mg initial dose was followed by 25 mg for 4 days (Group 2), or 10 mg for 5 days (Group 3).. Clinical cure was obtained in 27 patients of a total of 35 (77%) and six other patients improved (17%). Two patients at the lowest dose failed and both had very low plasma concentration of D0870. No association was found between clinical outcome; minimum inhibitory concentration of D0870 pre-therapy for Candida albicans, maximum recorded plasma D0870 concentration, cfu of culture or CD4 cell count at entry. Overall, 37% of the patients experienced relapse during the 2 weeks post therapy. Tolerance was excellent. Mild adverse events possibly related to the study drug were recorded in five patients.. D0870 demonstrates excellent efficacy at low doses in the treatment of HIV-related OPC and exhibits a favourable safety profile.

    Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Candida; Candida albicans; Candidiasis; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mouth Diseases; Recurrence; Treatment Outcome; Triazoles

1997

Other Studies

7 other study(ies) available for ici-195739 and Candidiasis

ArticleYear
Colorimetric MTT assessment of antifungal activity of D0870 against fluconazole-resistant Candida albicans.
    Mycoses, 1998, Volume: 41, Issue:11-12

    The in vitro antifungal activity of D0870 against eight isolates of fluconazole-resistant Candida albicans was compared with that of itraconazole, ketoconazole and miconazole. The colorimetric MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] assay was used to assess the antifungal activities. The 50% minimum inhibitory concentration (MIC50) of D0870 was below 0.031 microgram ml-1 for seven isolates and 0.25 microgram ml-1 for one isolate. The activity of D0870 was superior to that of the other azoles. Ketoconazole was the most effective azole next to D0870. Therefore, the new bis-triazole, D0870, is expected to be promising for the therapy of fluconazole-resistant candidosis. The present data also confirmed that the MTT assay may be useful for evaluation of resistance and detection of resistant C. albicans.

    Topics: Antifungal Agents; Candida albicans; Candidiasis; Colorimetry; Drug Resistance, Microbial; Fluconazole; Humans; Microbial Sensitivity Tests; Tetrazolium Salts; Thiazoles; Triazoles

1998
Variations in DNA subtype and antifungal susceptibility among clinical isolates of Candida tropicalis.
    Diagnostic microbiology and infectious disease, 1997, Volume: 27, Issue:3

    Candida tropicalis has been known to be a major cause of invasive Candida infection. Numerous reports have documented C. tropicalis as the most common species of Candida other than C. albicans. The epidemiology and antifungal susceptibility of C. tropicalis are poorly defined. A series of 89 clinical isolates of C. tropicalis from 56 patients hospitalized at seven different U.S. medical centers were analyzed by restriction endonuclease analysis of genomic DNA (REAG) using the restriction enzymes Sfil and BssHII followed by pulsed-field gel electrophoresis (PFGE). The MICs of the isolates for amphotericin B, 5-fluorocytosine (5FC), fluconazole, itraconazole, and D0870 were determined by microbroth dilution testing. A total of 49 different DNA types were identified among the 89 isolates. Generally, each DNA type represented an individual patient, and serial isolates from the same patient were the same DNA type. Small clusters of patients infected with the same DNA type of C. tropicalis suggested possible nosocomial transmission. The MICs of the various antifungal agents were amphotericin B 0.5 to 2.0 micrograms/ml (MIC90 = 2.0 micrograms/ml), 5FC 0.25 to 1.0 microgram/ml (MIC90 = 0.5 microgram/ml), fluconazole 0.25 to 8.0 micrograms/ml (MIC90 = 1.0 microgram/ml), itraconazole 0.03 to 1.0 microgram/ml (MIC90 = 0.5 microgram/ml), and D0870 0.007 to 0.12 microgram/ml (MIC90 = 0.03 microgram/ml). These data support previous observations that infections caused by C. tropicalis frequently originate from the patient's own endogenous flora. Clusters of a single strain in individual hospitals also suggests that limited nosocomial transmission may occur.

    Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; DNA, Fungal; Electrophoresis, Gel, Pulsed-Field; Fluconazole; Flucytosine; Humans; Itraconazole; Microbial Sensitivity Tests; Mycological Typing Techniques; Polymorphism, Restriction Fragment Length; Triazoles

1997
Efficacy of D0870 treatment of experimental Candida vaginitis.
    Antimicrobial agents and chemotherapy, 1997, Volume: 41, Issue:7

    In this study, oral administration of the triazole D0870 was compared to oral administration of fluconazole in the treatment of experimental vaginal candidiasis. With an estrogen-dependent murine model of Candida albicans vaginal infection, the effects of D0870 on several isolates, including fluconazole-susceptible and -resistant isolates, were tested. D0870, at doses of 0.5 and 2.5 mg/kg of body weight given once over the course of a 10-day infection, was effective in eradicating vaginitis caused by fluconazole-susceptible laboratory and clinical isolates, respectively. In contrast, a stricter treatment regimen (every 24 to 48 h) with 10 and 25 mg of fluconazole per kg was required to achieve similar reductions in vaginal fungal titers induced by the same isolates. Whereas fluconazole was consistently ineffective in infections induced by fluconazole-resistant isolates, as predicted by in vitro susceptibility tests, D0870 was effective, although a daily regimen of 25 mg/kg was required. Additional studies showed that despite the in vitro activity of D0870 against two clinical Candida glabrata isolates, neither D0870 nor fluconazole was effective at daily doses as high as 100 and 125 mg/kg, respectively. Taken together, although D0870 failed to show efficacy against experimental C. glabrata vaginitis, D0870 was superior to fluconazole in the treatment of experimental C. albicans vaginitis caused by isolates that were either susceptible or resistant to fluconazole.

    Topics: Animals; Antifungal Agents; Candidiasis; Drug Resistance, Microbial; Female; Fluconazole; Mice; Mice, Inbred CBA; Microbial Sensitivity Tests; Triazoles; Vaginitis

1997
Activities of D0870, a novel triazole, against Candida lusitaniae and Trichosporon beigelii in experimental murine infections.
    Antimicrobial agents and chemotherapy, 1995, Volume: 39, Issue:2

    Candida lusitaniae and Trichosporon beigelii may cause life-threatening infections in the immunocompromised host and may be resistant to amphotericin B. We assessed the activities of a new triazole, D0870, against one T. beigelii and four C. lusitaniae strains, in comparison with those of fluconazole and amphotericin B. Immunosuppressed CF1 mice, intravenously infected with each fungal strain, received 3 days of therapy with oral D0870 (5 or 25 mg/kg of body weight daily), fluconazole (5 to 50 mg/kg daily), or parenteral amphotericin B (1 or 2 mg/kg daily). Survival was significantly prolonged and kidney fungus titers were reduced in mice treated with D0870 compared with untreated mice (P < or = 0.05). Treatment with D0870 was significantly more effective than that with amphotericin B or fluconazole in animals infected with two of the C. lusitaniae strains and equally effective for the remaining two C. lusitaniae strains and the T. beigelii strain. Fluconazole and amphotericin B failed to improve the survival of mice infected with one and two C. lusitaniae strains, respectively. D0870 was active against all the organisms tested, including those resistant to fluconazole and amphotericin B.

    Topics: Animals; Antifungal Agents; Candida; Candidiasis; Male; Mice; Microbial Sensitivity Tests; Mycoses; Triazoles; Trichosporon

1995
Fluconazole, D0870, and flucytosine treatment of disseminated Candida tropicalis infections in mice.
    Antimicrobial agents and chemotherapy, 1995, Volume: 39, Issue:4

    D0870 is a recently developed triazole with characteristics of a broad spectrum of activity and slow clearance by nonrenal mechanisms. Herein we have evaluated the efficacy of D0870, alone and combined with flucytosine, in a murine model of disseminated Candida tropicalis infection. Four isolates of C. tropicalis were evaluated. Two were highly susceptible in vitro to fluconazole, and two were resistant to fluconazole. All were highly susceptible to flucytosine and D0870. Animals were pretreated with 5-fluorouracil 1 day before infection because C. tropicalis has reduced virulence in immunocompetent mice. This was done to render them neutropenic for > 10 days. Mice were infected intravenously and treated orally with D0870 or fluconazole, alone or combined with flucytosine. Survival and tissue burden of the spleen and kidneys were used to evaluate the efficacy of antifungal therapy. Fluconazole was less effective for treatment of resistant C. tropicalis than susceptible C. tropicalis. D0870 was more potent than fluconazole and was effective in fluconazole-resistant isolates. Flucytosine was consistently effective when used alone but did not consistently add to the benefit of D0870 or fluconazole. D0870 has potential in treatment of candidiasis caused by C. tropicalis, including fluconazole-resistant isolates.

    Topics: Animals; Antifungal Agents; Candidiasis; Drug Therapy, Combination; Fluconazole; Flucytosine; Mice; Mice, Inbred ICR; Triazoles

1995
Treatment of disseminated Torulopsis glabrata infection with DO870 and amphotericin B.
    Antimicrobial agents and chemotherapy, 1994, Volume: 38, Issue:7

    Torulopsis glabrata, an opportunist pathogen in immunosuppressed patients, is resistant to many antifungal agents, and there are no established treatment regimens for this organism. The mouse model was used to evaluate treatment with DO870, amphotericin B, fluconazole, and their combination. Mice were immunosuppressed with 5 mg of gold sodium thiomalate given intraperitoneally 1 day prior to intravenous infection with 10(8) T. glabrata cells. Treatment with a new antifungal triazole, DO870, at doses ranging from 1 to 50 mg/kg of body weight administered per os either daily or on alternate days; fluconazole at 100 mg/kg twice a day per os; or amphotericin B at 3 mg/kg/day intraperitoneally was begun 1 day after infection. Treatment for 5 days was followed by sacrifice 2 days later for determining CFU counts in spleen and kidney tissue. For a fluconazole-sensitive isolate (MIC of DO870, < 1.25 micrograms/ml), DO870 at 5 mg/kg/day significantly reduced counts in kidney and spleen tissue (P < 0.05), amphotericin B was modestly effective, and the combination of DO870 (25 mg/kg) and amphotericin B (3 mg/kg) was markedly more effective than either drug alone (P < 0.01). Three additional isolates were resistant in vitro to DO870 (MIC, 4 micrograms/ml). No reduction in CFU in kidney or spleen tissue was observed with DO870 when compared with counts in control tissue. DO870 is effective in vivo against at least some isolates of T. glabrata and when combined with amphotericin B can exert additive effects.

    Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Drug Synergism; Drug Therapy, Combination; Fluconazole; Immunosuppression Therapy; Kidney; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Spleen; Triazoles

1994
Candida albicans--do mycelia matter?
    Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology, 1990, Volume: 28, Issue:3

    Growth of Candida albicans in the mycelial phase is neither necessary for initiation of infection in the kidney of the mouse, following intravenous inoculation, nor for the establishment of chronic renal colonization. However, mycelial formation would appear to be important in the establishment of pelvic lesions with their associated pathological changes. Two mycelia-less mutants, CA-2 and MM2002, in the early stages of infection tended to develop in the glomeruli of the mouse kidney cortex while the wild-type parent strains spread throughout the cortex and medulla, with only occasional involvement of glomeruli. The mutants appeared to stimulate a milder inflammatory response than the parent strains. In chronic infections with wild-type strains, tangled masses of mycelia filled the renal pelvis, but pyelonephritis and hydronephrosis did not depend on a persistent cortical infestation. Yeasts of the mutant strains persisted in the body of the kidney and stimulated a continuing neutrophil response. Systemic infections with wild-type strains were eliminated by treatment with low doses of an azole antifungal drug, ICI 195,739, or with amphotericin B, whereas systemic infections with the mutant strains were much reduced, but not eliminated, by relatively high doses of either of the two drugs. Unlike azole drugs, amphotericin B does not show differential activity against the two morphological forms of C. albicans. Because kidney infections with the mutant strains are relatively resistant to amphotericin B as well as the azole tested, we conclude that the impressive activity of azoles in vivo may not be explained entirely by their inhibition of mycelial growth.

    Topics: Amphotericin B; Animals; Candida albicans; Candidiasis; Culture Media; Kidney Cortex; Kidney Diseases; Kidney Glomerulus; Mice; Triazoles

1990