Disease relevance of Fungata

• Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality [1].
• Amphotericin versus fluconazole in cryptococcal meningitis [2].
• There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25) [3].
• Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved [4].
• Fluconazole and Candida krusei fungemia [5].

Psychiatry related information on Fungata

• Itraconazole (intravenous 200 mg daily, or oral solution 2.5 mg/kg 3 times daily) and fluconazole (intravenous or oral, 400 mg daily) were administered with the start of conditioning therapy, until at least 120 days after SCT [6].
• Alcohol drinking, elevated CD8 lymphocyte counts and fluconazole therapy were associated with a decreased risk, and cigarette smoking with increased risk [7].
• We hypothesized that poor patient compliance with thrice-weekly fluconazole prophylaxis would correlate with the occurrence of clinical events [8].
• For both outcomes of total mortality and invasive fungal infections, almost all trials of fluconazole and ketoconazole separately showed a non-significant risk reduction with prophylaxis [9].
• These results demonstrate that by rapidly reducing the colonization of the alimentary tract, fluconazole eliminates the major reservoir for infection with yeasts other than C. glabrata and C. krusei during the critical period of neutropenia [10].

High impact information on Fungata

• Mutations of POR also affect drug-metabolizing P450 enzymes, explaining the association of ABS with maternal fluconazole ingestion [11].
• Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008) [12].
• RESULTS: The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, and base-line risk factors for fungal infection [12].
• Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks (95 percent confidence interval for the difference in percentages, -100 to 21) [13].
• There was no statistically significant difference in outcome: of the 103 patients treated with amphotericin B, 81 (79 percent) were judged to have been treated successfully, as were 72 of the 103 patients treated with fluconazole (70 percent P = 0.22; 95 percent confidence interval for the difference, -5 to 23 percent) [14].

Chemical compound and disease context of Fungata

• In addition, fluconazole is effective for selected patients with serious candida syndromes such as candidemia, and itraconazole is the most effective of the azoles for the treatment of aspergillosis [15].
• In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis [3].
• More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available [14].
• In a randomised, double-blind study the efficacy and toxicity of oral fluconazole 50 mg daily and ketoconazole 200 mg daily were compared for the treatment of oropharyngeal candidiasis in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) [16].
• CONCLUSION: Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS [17].

Biological context of Fungata

• Here we show that the C.albicans FK506 binding protein FKBP12 homolog is required for FK506 synergistic action with fluconazole [18].
• Computer analysis of the x-ray spectra allowed elemental microanalysis of the nucleus, cytoplasm, and late anaphase-early telophase chromatin regions in the cryptal and villus enterocytes [19].
• OBJECTIVE: To determine the effect of fluconazole on rifabutin pharmacokinetics [20].
• The three patterns of gene expression were also identified in fluconazole-resistant clinical isolates, providing further evidence that these patterns represent common programs of adaptation to fluconazole [21].
• By in situ analysis, methylation was patchy and located mainly in the cryptal regions close to the lumen [22].

Anatomical context of Fungata

• Prophylactic administration of fluconazole to recipients of bone marrow transplants reduces the incidence of both systemic and superficial fungal infections [4].
• Among the three, fluconazole has the most attractive pharmacologic profile, including the capacity to produce high concentrations of active drug in cerebrospinal fluid and urine [15].
• In contrast, KGF receptor transcripts were localized to the cryptal region of the mucosal epithelium in both normal and IBD tissue, with no apparent differences in the level of expression [23].
• Computer analysis of the X-ray spectra allowed elemental microanalysis of the nucleus, cytoplasm, and mitotic chromatin regions in the cryptal and villus enterocytes [24].
• The HFE protein was shown by immunohistochemistry to be expressed in certain epithelial cells throughout the human alimentary tract and to have a unique localization in the cryptal cells of small intestine, where signals to regulate iron absorption are received from the body [25].

Associations of Fungata with other chemical compounds

• There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001) [26].
• In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1) [27].
• The epithelial surface pH was 7.13 +/- 0.08 at the apex of mucosal villus and 7.42 +/- 0.11 (n = 5) in the cryptal area between the villi, i.e., greater than 1 pH unit higher than that of the luminal bulk solution (pH 6), thus suggesting active alkalization of the epithelial surface [28].
• In vitro susceptibility tests to fluconazole and ketoconazole were also performed [29].
• First, CRZ1 was not involved in tolerance to antifungal agents (fluconazole, terbinafine) on the opposite to calcineurin [30].

Gene context of Fungata

• Here we show that disruption of C. glabrata PDR1 conferred equivalent fluconazole hypersensitivity (MIC = 2 microg ml(-1)) to both F15 and 66032 and eliminated both constitutive and fluconazole-induced CDR1-PDH1 expression [31].
• Several clinical fluconazole-resistant isolates overexpress some Cka2p-responsive genes [32].
• In the current study, we investigated the effect of ketoconazole and other azole-derived drugs, miconazole and fluconazole, on the transcriptional activity of the human GR (hGR) in HeLa and HepG2 cells, and in primary human hepatocytes [33].
• The potency of fluconazole as a CYP3A4 inhibitor is much lower [34].
• We tested the susceptibility of ERG11 deletion strains of Saccharomyces cerevisiae (SC) expressing PCERG11, PCERG11-SDM, and wild-type SCERG11 to three azole antifungals: fluconazole, itraconazole, and voriconazole [35].

Analytical, diagnostic and therapeutic context of Fungata

• Prophylactic fluconazole and marrow transplantation [36].
• A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group [27].
• Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group [3].
• Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34) [3].
• We describe the unanticipated problems we encountered in collecting data for a meta-analysis comparing a new antifungal agent, fluconazole, with amphotericin B in patients with cancer complicated by neutropenia [37].

References