Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new diflucan research articles will be listed here shortly after becoming available to us.
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Medical research on diflucan
Mol Microbiol. 2008 May 27;
Dunkel N, Blaß J, Rogers PD, Morschhäuser J
Overexpression of the MDR1 gene, encoding a multi-drug efflux pump of the major facilitator superfamily, is a major cause of resistance to the widely used antifungal agent fluconazole and other toxic substances in the fungal pathogen Candida albicans. We found that all tested clinical and in vitro generated C. albicans strains that had become fluconazole-resistant by constitutive MDR1 upregulation contained mutations in the MRR1 gene, which encodes a transcription factor that controls MDR1 expression. Introduction of the mutated alleles into a drug-susceptible C. albicans strain resulted in activation of the MDR1 promoter and multi-drug resistance, confirming that the amino acid substitutions in Mrr1p were gain-of-function mutations that rendered the transcription factor constitutively active. The majority of the MDR1 overexpressing strains had become homozygous for the mutated MRR1 alleles, demonstrating that the increased resistance level conferred by two gain-of-function alleles provides sufficient advantage to select for the loss of heterozygosity in the presence of fluconazole both in vitro and within the human host during therapy. Loss of heterozygosity usually occurred by mitotic recombination between the two chromosome 3 homologues on which MRR1 is located, but evidence for complete loss of one chromosome and duplication of the chromosome containing the mutated MRR1 allele was also obtained in two in vitro generated fluconazole-resistant strains. These results demonstrate that gain-of-function mutations in MRR1 are the major, if not the sole, mechanism of MDR1 overexpression in fluconazole-resistant strains and that this transcription factor plays a central role in the development of drug resistance in C. albicans.
J Med Assoc Thai. 2008 Mar; 91(3): 309-15
Isipradit S
OBJECTIVE: To assess the efficacy of 2% fluconazole subconjunctival injection as an adjunctive treatment in severe recalcitrant fungal corneal ulcer. DESIGN: Retrospective, non-comparative interventional case series. MATERIAL AND METHOD: From January 2007 to August 2007, the present study included six eyes of six patients with severe fungal corneal ulcer that did not respond to therapy with topical antifungal drugs, oral itraconazole (200 mg) twice a day and 10 microg intracameral amphotericin B. All of them were treated with 0.5 ml of 2% fluconazole subconjunctival injection twice a day as adjunctive therapy for 5 days then once a day till 14 days RESULTS: Three patients were successfully treated within 14 days. Two patients partially responded, and one of them underwent evisceration. The last patient did not respond to treatment and enucleation was done. Severe local and systemic side effects were not found. CONCLUSION: 0.5 ml of 2% Fluconazole subconjunctival injection can be a very useful treatment as adjunctive therapy for severe fungal keratitis, with a few mild complications, especially in cases of impending perforation or post operative such as glue application for ruptured cornea.
Antonie Van Leeuwenhoek. 2008 Jun 24;
Galgóczy L, Papp T, Pócsi I, Hegedűs N, Vágvölgyi C
Strains of five dermatophyte species (Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton rubrum and Trichophyton tonsurans) were selected for testing against Penicillium chrysogenum antifungal protein (PAF) and its combination with fluconazole (FCZ). Inhibition of microconidia germination and growth was detected with MICs of PAF ranging from 1.56 to 200 mug ml(-1) when it was used alone, or at constant concentration (100 mug ml(-1)) in combination with FCZ at from 0.25 to 32 mug ml(-1). The MICs for FCZ were found to be between 0.25 and 128 mug ml(-1). PAF caused a fungicidal effect at 200 mug ml(-1) and reduced growth at between 50 and 200 mug ml(-1). Total growth inhibition with fungistatic activity was detected at 64 mug ml(-1) of FCZ for M. gypseum, T. mentagrophytes, and T. tonsurans, and at 32 mug ml(-1) FCZ for M. canis and T. rubrum. PAF and FCZ acted synergistically and/or additively on all of the tested fungi except M. gypseum, where no interactions were detected.
Ocular distribution of intravenously administered micafungin in rabbits.
J Infect Chemother. 2008 Jun; 14(3): 204-7
Suzuki T, Uno T, Chen G, Ohashi Y
The ocular distribution of micafungin (MCFG), which has antifungal activity against Candida and Aspergillus species, was followed after the systemic administration of MCFG in rabbits. After MCFG (10 mg/kg) plus fluconazole (FLCZ; 10 mg/kg) was administered intravenously, the rabbits were killed, and MCFG and FLCZ concentrations in retina-choroid, vitreous humor, and plasma were determined by high performance liquid chromatography or liquid chromatography/mass spectrometry. The mean concentrations of MCFG in the retina-choroid at 0.25, 0.75, 4, 8, and 24 h after administration were 20.18, 15.97, 13.19, 6.27, and 0.75 mug/g, respectively, and were comparable with the MCFG plasma concentrations. The MCFG concentrations in retina-choroid and plasma exceeded the minimal antifungal inhibitory concentrations for endophthalmitis, although MCFG was not detected in the vitreous humor. These results suggest that the intravenous administration of MCFG is an effective treatment for endogenous fungal endophthalmitis when the causative fungus is localized in the retina and choroid.
Reduced Biocide Susceptibility in Candida albicans Biofilms.
Antimicrob Agents Chemother. 2008 Jun 23;
Nett JE, Guite KM, Ringeisen A, Holoyda KA, Andes DR
Candida biofilm formation is common during infection and environmental growth. We tested the impact of three biocides (EtOH, H2O2, and SDS) on C. albicans, C. parapsilosis, and C. glabrata biofilms. Efficacy required higher concentrations than planktonic controls. Combination study of two biocides (EtOH and H2O2) and fluconazole, demonstrated enhanced efficacy.
Long-term use of fluconazole for verrucous plaques of cutaneous candidiasis in KID syndrome.
Eur J Dermatol. 2008 Jun 23; 18(4): 469-470
Mansur AT, Aydingöz IE, Uygur T, Gündüz S
J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jun 11;
Liu HX, He YQ, Hu Y, Liu Y, Zhang JW, Li W, Wang ZT, Yang L
A rapid and specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) method was developed for the qualitative and quantitative determination of UGT2B7 activity using 3'-azido-3'-deoxythymidine (AZT) as probe substrate in human liver microsomes (HLMs). The method was validated for the determination of AZT glucuronidation (AZTG) with respect to specificity, linearity, detection limit, recovery, stability, precision and accuracy. The chromatographic separation was achieved on a UPLC BEH C(18) column (50mmx2.1mm i.d., 1.7mum), with phase of acetonitrile-water (ratio 6:94). Selective ion reaction (SIR) monitor was specific for AZT, AZTG and I.S. The method was linear over the concentration range 0.5-500muM for AZTG in spiked HLMs. Good precision and accuracy were obtained for concentrations over the standard curve range. AZTG was stable at 4 degrees C for at least 72h in spiked liver microsomes samples. The method was successfully used to determine the kinetics of UGT activities toward AZT in HLMs. In addition, the method could determine the effects of fluconazole, a known UGT2B7 selective inhibitor, on AZTG in HLMs. Therefore, this method is suitable for in vitro studies using AZTG formation as an index reaction for UGT2B7 activity.
Biophys Chem. 2008 Jun 5;
Kumar RS, Arunachalam S
A new class of surfactant-cobalt(III) complex ions of the type, cis-[Co(X)(2)(C(14)H(29)NH(2))Cl](2+) (where X=ethylenediamine (en), or 2,2'-bipyridyl (bpy), or 1,10-phenanthroline (phen)) and cis-[Co(trien)(C(14)H(29)NH(2))Cl](2+) (trien=triethylenetetramine) were synthesized and characterized by IR, NMR, UV-visible electronic absorption spectra, elemental analysis and metal analysis. The critical micelle concentration (CMC) values of these surfactant-cobalt(III) complexes in aqueous solution were obtained from conductance measurements. Specific conductivity data (at 298, 308, 318 and 328 K) served for the evaluation of the temperature-dependent CMC and the thermodynamics of micellization (DeltaG(0)(m), DeltaH(0)(m) and DeltaS(0)(m)). Interactions between calf thymus DNA and the surfactant-cobalt(III) complexes in aqueous solution have been investigated by electronic absorption spectroscopy, emission spectroscopy and viscosity measurements. The electrostatic interactions, van der Waals interactions and/or partial intercalative binding have been observed in these systems. The surfactant-cobalt(III) complexes were screened for their antibacterial and antifungal activities against various microorganisms. The results were compared with the standard drugs, Ciprofloxacin and Fluconazole respectively.
J Enzyme Inhib Med Chem. 2008 Jun; 23(3): 347-51
Gopalakrishnan M, Sureshkumar P, Thanusu J, Kanagarajan V
Compound 26 is more potent against Escherichia coli. and 24 is more active against Staphylococcus aureus, beta-Heamolytic streptococcus, Vibreo cholerae, Salmonella typhii, and Shigella flexneri than the standard drug ciprofloxacin. Moreover, of all the compounds tested, 26 is more effective against Aspergillus flavus and Mucor, than the standard drug fluconazole.
Southeast Asian J Trop Med Public Health. 2008 May; 39(3): 492-5
Nadagir SD, Chunchanur SK, Halesh LH, Yasmeen K, Chandrasekhar MR, Patil BS
Oropharyngeal candidiasis (OPC) continues to be a common opportunistic infection in patients infected with Human Immunodeficiency Virus (HIV) and is predictive of increasing immunosuppression. Though Candida albicans remains the predominant isolate, a rise in the frequency of isolation of non-albicans Candida (NAC) species is being observed. The levels of virulence and the sensitivities to available antifungal drugs vary among these species. Of 340 HIV seropositive patients in this study, 132 (38.8%) had oral lesions suggestive of candidiasis. Samples were collected from the lesion using sterile cotton swabs. Isolation and speciation were done by standard techniques. Antifungal drug susceptibility testing was done by macro broth dilution. The total number of Candida isolates was 135, of which, 45 (33.3%) were NAC species and 90 were C.albicans (66.6%). Of the NAC species, C. dubliniensis was the predominant pathogen (22,48.9%). Antifungal susceptibility testing showed that 14 (31.1%) of the NAC species and 11 (12.2%) of C. albicans were resistant to fluconazole (MIC > 8 microg/ml). A very high MIC of > 32 microg/ml was noted among the NAC species resistant to fluconazole.