Diflucan
Carboxylic acid and phosphate ester derivatives of fluconazole: synthesis and antifungal activities.

Nam NH, Sardari S, Selecky M, Parang K.

Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 41 Lower College Road, Kingston, RI 02881, USA.

Two classes of fluconazole derivatives, (a) carboxylic acid esters and (b) fatty alcohol and carbohydrate phosphate esters, were synthesized and evaluated in vitro against Cryptococcus neoformans, Candida albicans, and Aspergillus niger. All carboxylic acid ester derivatives of fluconazole (1a-l), such as O-2-bromooctanoylfluconazole (1g, MIC=111 microg/mL) and O-11-bromoundecanoylfluconazole (1j, MIC=198 microg/mL), exhibited higher antifungal activity than fluconazole (MIC > or = 4444 microg/mL) against C. albicans ATCC 14053 in SDB medium. Several fatty alcohol phosphate triester derivatives of fluconazole, such as 2a, 2b, 2f, 2g, and 2h, exhibited enhanced antifungal activities against C. albicans and/or A. niger compared to fluconazole in SDB medium. For example, 2-cyanoethyl-omega-undecylenyl fluconazole phosphate (2b) with MIC value of 122 microg/mL had at least 36 times greater antifungal activity than fluconazole against C. albicans in SDB medium. Methyl-undecanyl fluconazole phosphate (2f) with a MIC value of 190 microg/mL was at least 3-fold more potent than fluconazole against A. niger ATCC 16404. All compounds had higher estimated lipophilicity and dermal permeability than those for fluconazole. These results demonstrate the potential of these antifungal agents for further development as sustained-release topical antifungal chemotherapeutic agents.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15519168&dopt=Abstract fluconazole Diflucan



Diflucan
Randomized comparison between fluconazole and itraconazole for the treatment of candidemia in a pediatric intensive care unit: a preliminary study.

Mondal RK, Singhi SC, Chakrabarti A, M J.

Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

OBJECTIVE: Candida bloodstream infections have shown an increase in hospitalized patients, especially those receiving intensive care. The effectiveness of various azoles, especially itraconazole, in treatment of candidemia has not been fully evaluated. Our objective was to compare the efficacy and safety of enterally administered itraconazole vs. fluconazole in treatment of candidemia. DESIGN: Randomized, double-blind, controlled trial. SETTING: Pediatric intensive care unit of a referral and teaching hospital. SUBJECTS: Forty-three pediatric patients with candidemia, INTERVENTION: Patients received either fluconazole (n = 22) or itraconazole (n = 21), about 10 mg/kg orally or through a gastric tube, and were monitored for clinical and mycological cure (sterile fungal blood culture), blood counts, and liver and renal functions. MEASUREMENTS AND MAIN RESULTS: The clinical characteristics of two groups were comparable. The cure rate was similar in both the groups: itraconazole 17 of 21 (81%) and fluconazole 18 of 22 (82%). Crude mortality rate (itraconazole 9.5% and fluconazole 13.6%) was also comparable in two groups of patients. The frequency of electrolyte disturbance was very low and similar in both the groups. Blood urea, creatinine, liver enzymes, and serum bilirubin were not adversely affected. CONCLUSIONS: Itraconazole was as effective as fluconazole in nosocomial candidiasis in children receiving intensive care and was devoid of serious side effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15530193&dopt=Abstract fluconazole Diflucan



Diflucan
In vitro fluconazole susceptibility of 1565 clinical isolates of Candida species evaluated by the disk diffusion method performed using NCCLS M44-A guidelines.

Testore GP, Dori L, Buonomini AR, Schito GC, Soro O, Fortina G, Andreoni S, Carlone N, Tullio V, Andreoni M.

University of Rome Tor Vergata, Department of Public Health, Rome, Italy.

We determined the in vitro activity of fluconazole against 1565 clinical Candida spp. isolates collected from different specimens of non-AIDS outpatients and inpatients in 3 different regions of Italy. Susceptibility testing was performed by agar disk diffusion using the NCCLS document M44-A guidelines. Candida albicans was the most frequently isolated yeast (68%) followed by C. glabrata (15%), C. tropicalis (5%), C. parapsilosis (5%), and C. krusei (5%). Other yeasts represented 4% of all isolates. Of the 1565 isolates tested, 1449 (92.6%) were susceptible (S) to fluconazole, 43 (2.7%) were susceptible dose-dependent (S-DD) and 73 (4.7%) were resistant (R). Almost all (98.2%) of the C. albicans isolates were classified as S or S-DD. Despite its widespread use, fluconazole displayed good activity against the isolates we tested, and the disk diffusion method was confirmed as a reliable approach to the evaluation of in vitro susceptibility of yeasts to this antimycotic agent.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15541604&dopt=Abstract fluconazole Diflucan



Diflucan
Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation.

van Burik JA, Ratanatharathorn V, Stepan DE, Miller CB, Lipton JH, Vesole DH, Bunin N, Wall DA, Hiemenz JW, Satoi Y, Lee JM, Walsh TJ; National Institute of Allergy and Infectious Diseases Mycoses Study Group.

University of Minnesota, Minneapolis, MN, USA.

We hypothesized that chemoprophylaxis with the echinocandin micafungin would be an effective agent for antifungal prophylaxis during neutropenia in patients undergoing hematopoietic stem cell transplantation (HSCT). We therefore conducted a randomized, double-blind, multi-institutional, comparative phase III trial, involving 882 adult and pediatric patients, of 50 mg of micafungin (1 mg/kg for patients weighing <50 kg) and 400 mg of fluconazole (8 mg/kg for patients weighing <50 kg) administered once per day. Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and as the absence of proven or probable IFI through the end of the 4-week period after treatment. The overall efficacy of micafungin was superior to that of fluconazole as antifungal prophylaxis during the neutropenic phase after HSCT (80.0% in the micafungin arm vs. 73.5% in the fluconazole arm [difference, 6.5%]; 95% confidence interval, 0.9%-12%; P=.03). This randomized trial demonstrates the efficacy of an echinocandin for antifungal prophylaxis in neutropenic patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15546073&dopt=Abstract fluconazole Diflucan



Diflucan
Rapid flow-cytometric susceptibility testing of Candida species.

Rudensky B, Broidie E, Yinnon AM, Weitzman T, Paz E, Keller N, Raveh D.

Clinical Microbiology Laboratory, and Infectious Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel.

OBJECTIVES: To develop a rapid flow-cytometric antifungal susceptibility test and to compare results with the standard methods. METHODS: Reference and laboratory strains of Candida were tested for susceptibility to fluconazole and echinocandin by fluorescent flow cytometry using Acridine Orange as indicator of viability. Flow cytometry results were compared with MICs as determined by macrodilution and/or Etest. RESULTS: Seventy Candida strains were tested for susceptibility to fluconazole, and 74 strains for susceptibility to echinocandin. Minimal concentration of fluconazole causing 40% cell damage, as determined by flow cytometry, showed excellent association with MIC, as determined by other methods. The flow method, completed within 5 h, had excellent sensitivity and specificity to distinguish between sensitive, susceptible dose-dependent and resistant strains. The flow cytometry method for echinocandin was completed within 3 h, and minimal concentration causing 50% cell damage was associated with MIC as determined by macrodilution. CONCLUSIONS: Antifungal susceptibility testing by FACS is a reliable, rapid method for determining susceptibility of Candida to fluconazole and echinocandin. The method allows same-day results, assisting in the selection of appropriate antifungal therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15546969&dopt=Abstract fluconazole Diflucan



Diflucan
Etest for assessing the susceptibility of filamentous fungi.

Doczi I, Dosa E, Varga J, Antal Z, Kredics L, Nagy E.

Department of Clinical Microbiology, Faculty of Medicine, University of Szeged, Somogyi Bela ter 1, H-6725 Szeged, Hungary.

The purpose of this study was to evaluate the Etest as an in vitro antifungal susceptibility test method for different moulds originating from human samples and from the environment. A total of 50 isolates (1 Acremonium, 18 Aspergillus, 2 Cladosporium, 1 Epicoccum, 15 Penicillium, 2 Scopulariopsis and 11 Trichoderma strains) were tested by the Etest. Forty-six of the tested moulds (92%) were resistant to fluconazole with minimal inhibitory concentrations (MICs) > or = 256 microg ml(-1). There were strains resistant to ketoconazole among Aspergillus niger, A. ochraceus and Cladosporium spp. with MICs > 32 microg ml(-1). For fluconazole, no differences were observed using two different inocula, while for itraconazole, ketoconazole and amphotericin B, a 1 or less step 2-fold dilution difference in MIC was seen for the most of 10 selected strains. The MICs of fluconazole and amphotericin B obtained for Trichoderma strains by the Etest and the agar dilution method were also compared. MICs for fluconazole were in agreement, while MICs for amphotericin B were higher with 1 or 2 steps of 2-fold dilutions for most of Trichoderma strains in the case of the agar dilution method.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15571067&dopt=Abstract fluconazole Diflucan



Diflucan
Successful public/private donation programs: a review of the Diflucan Partnership Program in South Africa.

Wertheimer AI, Santella TM, Lauver HJ.

Center for Pharmaceutical Health Services Research, Temple University School of Pharmacy, 3307 No. Broad Street, Philadelphia, PA 19140, USA. albert.wertheimer temple.edu

A review of the partnership between Pfizer Inc. and the South African Ministry of Health to distribute free Diflucan (fluconazole) in the Diflucan Partnership Program (DPP) demonstrates that product donations may be a useful response to AIDS if they are coupled with efforts to build means of drug distribution and enhance professional healthcare capacity to treat patients. Equally important is the creation of a new set of productive working relationships between stakeholders who came to the project with different backgrounds and perspectives, as well as a frankly disparate set of objectives. A decision tree illustrates how these relationships were built into the DPP. This review concludes with a few lessons learned in providing medicines not only to South Africa, but also to the 77 other African countries now participating in the DPP. As the search for new treatments and vaccines continues, increasing access to existing medicines through targeted donations--including training and infrastructure support--is the most practical way for the health community to address the problem of ill health among the poor. In addition to a detailed analysis of the DPP, there is also a discussion of the benefits of a donation program that addresses the AIDS crises on a global scale. This review may serve as a blueprint for establishing programs that are successful in fighting AIDS and improving the lives of millions of people.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15573711&dopt=Abstract fluconazole Diflucan



Diflucan
Comparison of antifungal susceptibilities to fluconazole and voriconazole of oral Candida glabrata isolates from head and neck radiation patients.

Burn AK, Fothergill AW, Kirkpatrick WR, Coco BJ, Patterson TF, McCarthy DI, Rinaldi MG, Redding SW.

Department of General Dentistry, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA. burn uthscsa.edu

The antifungal susceptibilities of 79 oral Candida glabrata isolates to fluconazole and voriconazole were compared. The MICs at which 90% of the isolates tested were inhibited were 1 microg of voriconazole/ml and 32 microg of fluconazole/ml. Oral C. glabrata isolates for which the fluconazole MICs are elevated are commonly those for which the voriconazole MICs are elevated, but these increases may be transient for voriconazole, as they are for fluconazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15583322&dopt=Abstract fluconazole Diflucan