SEARCH · PubMed Health

Results for “Fluconazole”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1992

Combined effect of fluconazole and recombinant human interleukin-1 on systemic candidiasis in neutropenic mice.

The aim of the present study was to investigate the efficacy of treatment with a combination of fluconazole and human recombinant interleukin-1 alpha (IL-1 alpha) in normal or neutropenic mice with systemic Candida albicans infection. Six hours after intravenous injection of 5 x 10(4) CFU of C. albicans organisms, oral treatment twice daily with 2.5 or 10 mg of fluconazole per kg of body weight, a single intraperitoneal injection of 80 ng of IL-1, or a combination of the two was started. IL-1 had no influence on the antifungal activity of fluconazole in vitro or on the pharmacokinetics of fluconazole. For both normal and neutropenic mice, the number of C. albicans organisms cultured from the kidneys after 36 h of treatment was significantly lower in mice treated with IL-1 alone than in untreated animals. Treatment with fluconazole alone also significantly lowered the number of C. albicans organisms in the kidneys compared with that in untreated controls. In normal mice, the combination of fluconazole and IL-1 was not better than fluconazole alone. In neutropenic mice, combined treatment with IL-1 and 10 mg of fluconazole per kg led to significantly lower numbers of C. albicans organisms in the kidneys and the spleen than treatment with either agent alone. Although the precise mechanism by which IL-1 enhances resistance to infection is not clear, the additive effect of IL-1 and fluconazole in vivo indicates that combined therapy with immunomodulators and antifungal drugs is beneficial in immunocompromised mice with systemic fungal infections.

Animals↗

PubMed1992

Intraocular penetration and effect on the retina of fluconazole.

The intraocular concentration of fluconazole was measured in nonvitrectomized and vitrectomized eyes after an intravenous administration of 5 or 25 mg/kg fluconazole in albino rabbits. Respective fluconazole concentrations in the aqueous, vitreous and serum 1 hour after administration were 2.87, 1.72 and 4.60 micrograms/ml at 5 mg/kg administration, and 14.93, 7.05 and 20.63 micrograms/ml at 25 mg/kg administration, indicating high and dose-dependent intraocular penetration of fluconazole. Intraocular penetration of intravenously administered fluconazole was moderately, not very much, enhanced by vitrectomy. The in-vitro electroretinogram (ERG) remained unchanged after perfusion with 20 micrograms/ml of fluconazole. The in-vivo ERG and the visual evoked potential was unchanged after the daily administration of 25 mg/kg fluconazole for 8 days. The toxicity of fluconazole on the retina would be low and within safety limits so far as it is used at clinical dosage. Fluconazole may have a place in the treatment of fungal ocular infections.

Animals↗

PubMedDate not supplied

Prophylaxis and treatment of fungal infections with fluconazole in bone marrow transplant patients.

In an open study 31 patients undergoing bone marrow transplantation for various haematological diseases received fluconazole as prophylaxis or treatment of fungal infections. In 26 of these patients an antecedent oral prophylaxis with polyene antimycotics had failed to prevent infections with Candida species. Five of the 31 patients received fluconazole as primary prophylaxis because of non-compliance for polyene antimycotics. Fluconazole was administered orally at a daily dose of 100 mg and 200 mg, respectively (n = 29), or intravenously at a dose of 100 mg and 400 mg (n = 2). Cure or efficient prophylaxis was achieved in 22/31 patients (71%) after a median of 52 (9 to 493+) treatment days. In three patients (10%) Candida was eradicated but the infection reappeared 14-28 days after cessation of the drug; in 6 patients (20%) the infection was persistent or progressive. Four patients developed lethal Aspergillus infection while on fluconazole medication. A moderate and reversible elevation of liver function tests under therapy was observed in 9 patients and was possibly attributable to fluconazole in three of them (10%). One patient developed tremor which resolved after cessation of fluconazole. No other adverse drug reactions could be noted. We conclude that fluconazole is a relatively safe and effective drug for the prevention and treatment of superficial and, possibly, deep Candida infections in severely immunocompromised patients. However, it is presumably without preventive value in Aspergillus infections.

Adult↗

PubMed1992

Effects of culture media on the in vitro susceptibility of selected opportunistic fungi to fluconazole and itraconazole.

The sensitivity of 23 isolates of opportunistic fungi, Aspergillus fumigatus (5), A. flavus (5), A. niger (5), Pseudallescheria boydii (5), Alternaria alternata (2) and Xylohypha bantiana (1), was investigated against fluconazole and itraconazole, using Sabouraud's dextrose broth (SD) and a high-resolution (HR) medium (Pfizer, Inc.). The procedure followed was a standard tube dilution (1 ml/tube) method. Candida albicans Y01 09 was included as reference strain to monitor quality and reproducibility. Results indicated that the minimal inhibitory concentrations (MICs) of fluconazole for all Aspergillus spp. and C. albicans were greater than or equal to 100 micrograms/ml in SD medium, whereas, for P. boydi, A. alternata and X. bantiana, the MICs were 50 micrograms/l. The MICs of itraconazole in SD medium were less than 0.195-1.56 micrograms/ml for the fungi tested. In HR medium, the MICs of fluconazole for the Aspergillus spp, were greater than or equal to 100 micrograms/ml, and those for P. boydii, A. alternata and X. bantiana were 0.78, 50 and 50 micrograms/ml, respectively. The MICs of itraconazole for all fungi ranged from less than 0.198 to 0.78 micrograms/ml in the HR medium. The values for the reference strain were 1.56 and 100 micrograms/ml in the HR medium for fluconazole and itraconazole, respectively. The HR medium was more suitable for testing P. boydii against fluconazole. This culture medium did not appear to significantly affect the MICs of itraconazole as compared to those of fluconazole, for the fungi investigated.

Alternaria↗

PubMed1992

Efficacy of fluconazole in the treatment of systemic fungal infections.

The efficacy of fluconazole in the treatment of systemic fungal infections was evaluated in an open non-comparative trial. A total of 48 patients with proven or suspected fungal infections were enrolled in 40 of whom efficacy was evaluable. Candida albicans accounted for 90% of the infections. Candida parapsilosis, Candida glabrata, Histoplasma capsulatum and Aspergillus fumigatus caused the infection in one case each. Fluconazole was administered at a dosage of 200-400 mg daily for a mean duration of 15 days. Fluconazole treatment was successful in 53% of the patients. In patients with proven or probable Candida albicans infections a clinical and mycological response was achieved in 62% and 65%, respectively. In 11 patients elevation of liver enzymes was considered to be possibly related to fluconazole treatment; modification of treatment was not necessary in any case. Fluconazole was found to be a well tolerated and effective agent for the treatment of systemic Candida albicans infections.

Adolescent↗

PubMed1992

Effects of fluconazole on the sterol and carbohydrate composition of four species of Candida.

The effects of fluconazole, a bis-triazole antifungal agent, on the sterol and carbohydrate composition of Candida albicans, Candida tropicalis, Candida krusei and Candida parapsilosis were investigated. Exposure of Candida species to fluconazole resulted in a profound depletion of ergosterol with a corresponding increase in lanosterol content versus control cells. Carbohydrate analysis revealed a significant increase in chitin and either a decrease (Candida albicans, Candida tropicalis and Candida parapsilosis) or an increase (Candida krusei) in glucan content in fluconazole-treated cells. The decreased ergosterol and increased lanosterol content is consistent with 14-alpha-demethylase inhibition by fluconazole. The increase in cell wall chitin is most likely due to deregulation of chitin synthesis secondary to ergosterol depletion in the cell membrane. Because chitin, glucan and ergosterol are critical components of the fungal cell, perturbation of the production and localization of these components by fluconazole is likely to contribute to the selective toxicity of this compound to Candida species and other fungi.

Candida↗

PubMed1992

Persistence of the same Candida albicans strain despite fluconazole therapy. Documentation by pulsed-field gel electrophoresis.

Candida albicans and other Candida species have emerged as major nosocomial pathogens associated with a high mortality. Therapeutic options for fungal infections are limited. Amphotericin B has been the mainstay of treatment for serious systemic candidal infections, but it is relatively toxic and associated with a variety of side effects. Fluconazole has been proposed as alternative therapy for the treatment of systemic candidiasis including candidemia. We report the case of a patient with fungemia in whom fluconazole failed to eradicate C. albicans and C. tropicalis. These pathogens were recovered from sputum and urine cultures, respectively, on day 12 of intravenous fluconazole therapy. Molecular epidemiologic techniques employing pulsed-field gel electrophoresis confirmed the persistence of the same C. albicans strain. Susceptibility studies showed a marked change in MICs of fluconazole between 24 and 48 hr, with an increase from less than or equal to 1.25 to greater than 80 micrograms/ml. Controlled trials will be needed to delineate the role of fluconazole in the treatment of disseminated candidiasis and its efficacy in comparison with amphotericin B. Amphotericin B should remain the drug of choice for such infections until data from controlled trials are available.

Candida↗

PubMed1992

Biliary concentrations of fluconazole in a patient with candidal cholecystitis: case report.

A patient with acute cholecystitis due to Candida albicans and Candida parapsilosis was treated with a percutaneous cholecystostomy and daily intravenous fluconazole. Fluconazole levels in serum and bile were measured by gas chromatography. Fluconazole levels in the bile were equal to those in the blood for the first 8 hours after a dose and were slightly higher than serum levels after that. Bile levels after an oral dose of fluconazole were 15% higher than levels achieved after intravenous administration of the drug. The infection was cured after 2 weeks of treatment. This experience suggests that sufficient fluconazole is excreted in the bile to be effective for treatment of biliary infections due to susceptible yeasts.

Aged↗

PubMed1992

Modulation of interactions of Candida albicans and endothelial cells by fluconazole and amphotericin B.

Using an in vitro model of intravascular infection, we examined the effects of exposure to subinhibitory concentrations of fluconazole and amphotericin B on the ability of Candida albicans to adhere to and damage human umbilical vein endothelial cells. Incubation of the organisms for 18 h in 0.5x the MICs of fluconazole and amphotericin B inhibited endothelial cell adherence by 22 and 91%, respectively (P less than 0.001 for each drug). Candida-induced endothelial cell injury was also decreased by exposing the organisms to the antifungal drugs while in contact with the endothelial cells. Fluconazole inhibited damage by approximately 50% at concentrations ranging from 0.25x to 5x the MIC (P less than 0.01 for each concentration). Exposure to amphotericin B at 0.5x the MIC completely blocked the ability of the organisms to injure endothelial cells. The capacities of the antifungal agents to inhibit endothelial cell injury paralleled their abilities to suppress candidal germination. Organisms exposed to up to 5x the MIC of fluconazole had diminished, but still detectable, germ tube production and elongation, whereas incubation in 0.5x the MIC of amphotericin B completely abrogated germination. In addition to their direct effects on the growth of C. albicans, fluconazole and amphotericin B may decrease the ability of the fungus to disseminate hematogenously by inhibiting the organisms' capacity to adhere to and injure endothelial cells.

Amphotericin B↗

PubMed1992

Fluconazole compared with ketoconazole for the treatment of Candida esophagitis in AIDS. A randomized trial.

OBJECTIVE: To determine the clinical and endoscopic response of candida esophagitis to antifungal therapy and to compare the two oral antifungal agents, fluconazole and ketoconazole. DESIGN: Multicenter, randomized, double-blind trial. SETTING: Fifteen U.S. centers including university, private practice, and county hospital settings. PATIENTS: A total of 169 patients with the acquired immunodeficiency syndrome (AIDS); odynophagia, dysphagia, or retrosternal pain; white esophageal plaques at endoscopy; and pseudohyphae on esophageal brushings or biopsies. INTERVENTION: Patients were randomly assigned to fluconazole (100 mg/d) or ketoconazole (200 mg/d). Doses were doubled at week 1 or 2 if no symptomatic improvement had occurred during the preceding week. Therapy was continued for 2 weeks after resolution of symptoms or for a maximum of 8 weeks. MEASUREMENTS: Patients were clinically evaluated weekly, and laboratory tests were done every 2 weeks. Endoscopy was repeated within 5 days after the end of therapy. RESULTS: A total of 143 patients were clinically evaluable (assessed within 7 days after therapy), and 129 patients were endoscopically evaluable (endoscopy repeated after therapy). Endoscopic cure occurred in 91% of patients treated with fluconazole and in 52% of those given ketoconazole for a difference of 39% (95% Cl, 24% to 52%; P less than 0.001). Esophageal symptoms resolved in 85% of fluconazole-treated patients and in 65% of ketoconazole-treated patients for a difference of 20% (Cl, 6% to 34%; P = 0.006). Intention-to-treat analyses also yielded statistically significant differences for the comparisons listed above. Side effects were minimal and comparable in the two groups; only one patient in each group had therapy discontinued for adverse effects that were possibly related to the study medications. CONCLUSIONS: Fluconazole is associated with significantly greater rates of endoscopic and clinical cure than ketoconazole in patients with AIDS and candida esophagitis. Both drugs appear to be safe and well tolerated.

Acquired Immunodeficiency Syndrome↗

PubMed1992

[In vitro evaluation of the sensitivity to fluconazole of different species of yeasts isolated in pathology].

In a previous study, the authors developed a technique for evaluating the in vitro susceptibility (or resistance) of Candida albicans to fluconazole, using casitone broth and agar. Photometric readings of growth in liquid media proved more accurate for evaluating antifungal activity and consistently agreed with clinical findings in all studied cases. This method was consequently extended from C. albicans to other yeasts recovered from high-risk patients (C. glabrata, C. famata, C. tropicalis, C. krusei, C. pseudotropicalis, C. parapsilosis, etc...). High resolution antifungal assay medium (broth and agar) and casitone medium (broth and agar) with or without agitation (Autobac System) were used to study the activity of fluconazole against approximately one hundred yeast strains. MICs above 3.12 micrograms/ml were found for several strains, particularly belonging to the C. glabrata and C. krusei species. These values are equal to or greater than serum levels achieved during treatment with fluconazole, a fact which raises practical questions concerning fluconazole therapy and may explain the failure of fluconazole to eradicate yeasts in some patients.

Candida↗

PubMed1992

Primary prophylaxis with fluconazole against systemic fungal infections in HIV-positive patients.

OBJECTIVE: To investigate the efficacy of fluconazole prophylaxis against systemic fungal infections in HIV-positive patients. DESIGN: Open label treatment compared with historical controls. SETTING: Patients were seen at the Parkland Memorial Hospital HIV Clinic, Dallas, Texas, USA between 1 March 1990 and 28 February 1991. PATIENTS, PARTICIPANTS: Three hundred and thirty-seven historical controls were followed for 157 patient-years, and 329 fluconazole-treated patients for 145 patient-years. INTERVENTIONS: Fluconazole (100 mg daily) was administered to all patients with CD4 lymphocyte counts less than 68 x 10(6)/l seen at our HIV clinic after 1 March 1990. MAIN OUTCOME MEASURES: Lysis-centrifugation blood cultures were recorded monthly for all patients during both study periods. RESULTS: Twenty infections (16 cryptococcosis, four histoplasmosis) occurred in 337 historical reference control patients (product-limit 1-year incidence, 7.5 +/- 2.0/year). Four infections (one cryptococcosis, three histoplasmosis) occurred in the treated patient group (product-limit 1-year incidence, 1.8 +/- 0.9/year). CONCLUSIONS: Fluconazole warrants further evaluation for prophylaxis against systemic fungal infections in HIV-positive patients.

Adult↗

PubMedDate not supplied

Shorter treatment for vaginal candidosis: comparison between single-dose oral fluconazole and three-day treatment with local miconazole.

Fluconazole is an effective, simple and safe, although slightly expensive, agent for the treatment of vaginal candidosis. Single-dose fluconazole (150 mg) administered orally in capsule form was compared with three-day local treatment with miconazole pessaries in the treatment of vaginal candidosis in a randomized study in Finland. Cure rates were good (> 80%) in randomized patient groups assessed both clinically and by the results of yeast cultures. Oral administration was preferred to local therapy by patients in both the miconazole and fluconazole groups. For the time being, fluconazole is not recommended for use during pregnancy or lactation.

Administration, Oral↗

PubMed2025

Landscape of essential growth and fluconazole-resistance genes in the human fungal pathogen Cryptococcus neoformans.

Fungi can cause devastating invasive infections, typically in immunocompromised patients. Treatment is complicated both by the evolutionary similarity between humans and fungi and by the frequent emergence of drug resistance. Studies in fungal pathogens have long been slowed by a lack of high-throughput tools and community resources that are common in model organisms. Here we demonstrate a high-throughput transposon mutagenesis and sequencing (TN-seq) system in Cryptococcus neoformans that enables genome-wide determination of gene essentiality. We employed a random forest machine learning approach to classify the C. neoformans genome as essential or nonessential, predicting 1,465 essential genes, including 302 that lack human orthologs. These genes are ideal targets for new antifungal drug development. TN-seq also enables genome-wide measurement of the fitness contribution of genes to phenotypes of interest. As proof of principle, we demonstrate the genome-wide contribution of genes to growth in fluconazole, a clinically used antifungal. We show a novel role for the well-studied RIM101 pathway in fluconazole susceptibility. We also show that insertions of transposons into the 5' upstream region can drive sensitization of essential genes, enabling screenlike assays of both essential and nonessential components of the genome. Using this approach, we demonstrate a role for mitochondrial function in fluconazole sensitivity, such that tuning down many essential mitochondrial genes via 5' insertions can drive resistance to fluconazole. Our assay system will be valuable in future studies of C. neoformans, particularly in examining the consequences of genotypic diversity.

Cryptococcus neoformans↗

PubMed1992

Subcellular distribution and antifungal effects of fluconazole in human phagocytic cells. Demonstration of the antifungal agent in neutrophil polymorphonuclear leucocytes and monocytes by autoradiography and electron micrography.

Electron microscopic autoradiography was used to demonstrate the presence of [3H] fluconazole (CAS 86386-73-4) in neutrophils and monocytes isolated from volunteers. Quantitative analysis of the autoradiographs showed significant accumulation of fluconazole in both phagocytic cells. The distribution of fluconazole was equal in the different intracellular compartments such as cytoplasm and nucleus. Fluconazole (20 micrograms/ml) induced ultrastructural changes in Candida albicans cells which had been phagocytized by neutrophils or monocytes (macrophages) in vitro. Particularly, changes in the plasma membrane and in the cytoplasmic structure of the intraphagocytic yeast cells were observed electron microscopically.

Antifungal Agents↗

PubMed1992

The comparative efficacy of cilofungin, fluconazole and amphotericin B in disseminated Candida tropicalis infection in neutropenic mice.

There is insufficient in vivo data on the efficacy of new antifungal agents against invasive Candida tropicalis infection. Disseminated infection with Candida tropicalis in neutropenic mice was treated with cilofungin, fluconazole, or amphotericin B intraperitoneally, and compared to untreated controls. Early survival rates at the end of treatment (day 10) were similar for amphotericin B (97.5%) and fluconazole (100%), and superior to cilofungin (62.6%) which was better than no treatment (0%). Late survival rates (day 31) were highest for amphotericin B (95%), and significantly lower for cilofungin (48.7%) and fluconazole (43.9%), p = 0.0001. Rates of sterilization of the lung, liver, and spleen were high in survivors for all regimens (85.1-100%) but lower for the kidneys: fluconazole, 21.3%; amphotericin B, 39.3%; and cilofungin, 65.5%. Amphotericin B was the most effective agent in this study of disseminated Candida tropicalis (C. tropicalis) infection.

Amphotericin B↗

PubMed1992

Single dose oral fluconazole vs intravaginal terconazole in treatment of Candida vaginitis. Comparison and pilot study.

Candida vaginitis develops in approximately one-fourth of women in their childbearing years. Conventional management consists of antifungal creams or tablets/suppositories administered intravaginally. Many patients have stated preferences for oral therapy. A randomized, double-blind placebo trial compared the efficacy of a single oral 200 mg dose of fluconazole with the application of terconazole 80 mg vaginal suppository daily for 3 days. Twenty-two patients (fluconazole = 12, terconazole = 10) were evaluated during a four-month period and favorable clinical responses were observed at both early and late evaluations. Mycologic cure was attained by 75% of the fluconazole group and 50% of the terconazole group at the early evaluation. At the late evaluation, mycologic cure was 75% and 100% respectively. The mean time to onset of symptom relief was 2.4 (1.7) days for the fluconazole group and 1.8 (1.8) days for the terconazole group. The mean time to complete relief of symptoms was 6.08 (2.84) and 6.6 (2.95) days respectively. A statistically significant difference did not exist for any of these measures. Seventy-three percent of the patients preferred oral therapy.

Administration, Intravaginal↗

PubMed1992

[Comparative clinical study of a new imidazole molecule (fluconazole) and ketaconazole in the treatment of Candida albicans vulvovaginitis].

A multicentre trial was carried out in Italy with the aim of comparing the efficacy, safety and tolerability of the oral administration of fluconazole with the oral administration of ketoconazole in the treatment of patients affected by Candida vulvovaginitis. A total of 174 patients with symptomatic Candida vulvovaginitis were identified both by objective examination and cell culture tests: of these 87 were treated using a single oral administration of fluconazole (150 mg) whereas the other 87 received 2 200 mg capsules of ketoconazole daily for 5 days. Tests to assess the efficacy, safety and tolerability of both treatments were carried out approximately 7 days and 5-6 weeks from the start of therapy. The results obtained showed a success rate of 92% for fluconazole-treated patients and 83% for those treated with ketoconazole. In addition to the rapid and safe efficacy of treatment, the most important findings which emerged from this study were the extreme simplicity of use, excellent patient compliance and the complete absence of collateral effects of variations in the hematochemical and urine parameters taken into consideration caused by fluconazole.

Adult↗