Fluconazole

Fluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections.

Primary Prophylaxis for Cryptococcosis With Fluconazole in Human Immunodeficiency Virus-Infected Patients With CD4 T-Cell Counts <100 Cells/microL and Receiving Antiretroviral Therapy.[Pubmed:28362939]

Clin Infect Dis. 2017 Apr 1;64(7):967-970.

A prospective observational cohort study was conducted in 302 human immunodeficiency virus-infected patients who had a CD4 T-cell count <100 cells/microL and negative serum cryptococcal antigen initiating antiretroviral therapy in a resource-limited setting. During 2-year follow-up, there were no differences of survival rates and occurrences of newly diagnosed cryptococcosis between patients with and without Fluconazole for primary prophylaxis of cryptococcosis.

Oral mucositis caused by Candida glabrata biofilms: failure of the concomitant use of fluconazole and ascorbic acid.[Pubmed:28357061]

Ther Adv Infect Dis. 2017 Jan;4(1):10-17.

OBJECTIVES: Candida glabrata is becoming one of the most prevalent pathogenic yeasts in cases of oral diseases. Mucositis is an recurrent oral infection in immunocompromised patients, and the actual guidelines recommend the use of Fluconazole (Flu) for many cases. However, the azole resistance by C. glabrata is renowned, causing a reduced therapeutic response, especially when it occurs in biofilms. In this study, we performed an in vitro evaluation of an alternative pharmacotherapy for C. glabrata biofilm infections, combining ascorbic acid (AA) with Flu. AA is recognized for degrading beta-glucans, an important compound of the biofilm matrices, which prevent drug diffusion. MATERIALS AND METHODS: Routine clinical 30 or 40 mg/l doses of Flu were applied to C. glabrata biofilms simultaneously with 200 or 300 mg/l of AA. RESULTS: The results showed that this combination effectively promoted the degradation of the biofilm network, but unfortunately, also stimulated the growth of the yeasts population due to release of several glucose monomers during beta-glucans hydrolysis. DISCUSSION: AA lead to the hydrolysis of the beta-glucans of the matrix, liberating glucose molecules which are used as carbon souce by the yeasts, thus suppressing the desired antifungal effect of the drug combination with Flu. CONCLUSIONS: Unlike to what happens in treatment of bacterial infection, AA should not be used together with Flu in the treating oral mucositis caused by Candida.

Regression analysis and categorical agreement of fluconazole disk zone diameters and minimum inhibitory concentration by broth microdilution of clinical isolates of Candida.[Pubmed:28363817]

J Mycol Med. 2017 Jun;27(2):220-226.

AIM AND OBJECTIVES: Rampant use of Fluconazole in Candida infections has led to predominance of less susceptible non-albicans Candida over Candida albicans. The aim of the study was to determine if zone diameters around Fluconazole disk can be used to estimate the minimum inhibitory concentration (MIC) for clinical isolates of Candida species and vice versa. Categorical agreement between the Clinical & Laboratory Standards Institute (CLSI) recommended disk diffusion and CLSI broth microdilution method was sought for. MATERIAL AND METHODS: Antifungal susceptibility testing by disk diffusion and Broth microdilution was done as per CLSI document M44-S3 and CLSI document M27-S4 for Candida isolates respectively. Regression analysis correlating zone diameters to MIC value was done. Pearson's correlation coefficient was calculated to determine correlation between disk zone diameters and MICs. RESULTS: Candida albicans (33.3%) was clearly outnumbered by other non-albicans species predominantly Candida tropicalis (42.5%) and Candida glabrata (18.4%). Ten percent of the strains were resistant to Fluconazole by disk diffusion and 13% by broth microdilution. MIC range for Candida albicans and Candida tropicalis ranged from

Clinical impact and management of fluconazole discontinuation on sirolimus levels in bone marrow transplant patients.[Pubmed:28355970]

J Oncol Pharm Pract. 2018 Apr;24(3):235-238.

Sirolimus, an immunosuppressant, is indicated post-allogeneic stem cell transplant to reduce the risk of graft-versus-host-disease. Sirolimus is metabolized by cytochrome P450 3A4 and is a substrate of the P-glycoprotein (P-gp) drug efflux pump. Interactions with known inhibitors of the CYP3A4 enzyme and P-glycoprotein, such as Fluconazole, are anticipated. Co-administration of Fluconazole leads to an increase in sirolimus blood concentrations due to an inhibition of metabolism. The discontinuation of Fluconazole will likely result in a decline in sirolimus blood concentrations, leaving patients at risk of graft-versus-host-disease. We report on three patients managed by the Hematology, Oncology Blood and Marrow Transplant Program at the Alberta Children's Hospital. The discontinuation of Fluconazole showed a marked reduction in sirolimus trough levels, requiring >200% increase in sirolimus dose to achieve therapeutic levels.

Azole antifungal agents: emphasis on new triazoles.[Pubmed:2831809]

Antimicrob Agents Chemother. 1988 Jan;32(1):1-8.

Many advances have been made in antifungal therapy over the last three decades. Itraconazole and Fluconazole, two investigational triazole agents, are the most recent additions to the list of antifungal drugs. This review has focused primarily on their mechanisms of action, favorable pharmacologic properties, and spectra of activity against a broad range of systemic pathogens. Itraconazole and Fluconazole show much promise as orally active agents, with less potential for toxicity than the currently available azoles. Fluconazole and, to a lesser degree, itraconazole are especially promising therapies for cryptococcal meningitis. In addition, Fluconazole may prove to be highly effective in urinary tract infections caused by Candida species and other fungi. Ongoing and future clinical trials will more clearly define the specific roles of itraconazole and Fluconazole in the treatment of systemic mycoses.