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Sample records for parte fluconazol itraconazol

  1. Fluconazole and itraconazole in pityriasis versicolor

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    Jaswal Ritu

    1999-01-01

    Full Text Available Pityriasis versicolor is a common superficial fungal infection caused by Malassezia species. It has a high incidence and prevalence in tropical climates. Although it responds well to treatment, relapses and recurrences are frequent. In the present study the therapeutic response of single dose fluconazole (400 mg with itraconazole (100mg twice daily ? 7 days was compared in sixty patients of pityriasis versicolor. No significant statistical difference (p>0.05% was observed between efficacy of two drugs. Therapy with fluconazole is preferable in view of single dose administration and lesser cost as compared to itraconazole.

  2. Effects of Cytochrome P 450 Inhibitors on Itraconazole and Fluconazole Induced Cytotoxicity in Hepatocytes

    International Nuclear Information System (INIS)

    Somchit, N.; Ngee, C.S.; Yaakob, A.; Ahmad, Z.; Zakaria, Z.A.

    2009-01-01

    Itraconazole and fluconazole have been reported to induce hepatotoxicity in patients. The present study was designed to investigate the role of cytochrome P450 inhibitors, SKF 525A, and curcumin pretreatment on the cytotoxicity of antifungal drugs fluconazole and itraconazole. For 3 consecutive days, female rats were administered daily SKF 525A or curcumin (5 and 25?mg/kg). Control rats received an equivalent amount of dosed vehicle. The animals were anaesthetised 24 hours after receiving the last dose for liver perfusion. Hepatocytes were then exposed to various concentrations of antifungal drugs. In vitro incubation of hepatocytes with itraconazole revealed significantly lower viability when compared to fluconazole as assessed by lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase activities. The cytotoxicity of itraconazole was enhanced when incubated with hepatocytes pretreated with SKF 525A. SKF 525A had no effects on the cytotoxicity of fluconazole. Curcumin failed to either increase or decrease the cytotoxicity of both antifungal drugs. ATP levels also showed significant decrease in both itraconazole and fluconazole incubated hepatocytes. However, SKF 525A pretreated hepatocytes had significantly lower ATP levels after itraconazole incubations. Collectively, these results confirm the involvement of cytochrome P450 in the cytoprotection in itraconazole induced hepatocyte toxicity. Differences of the effects of SKF 525A on the cytotoxicity induced by itraconazole and fluconazole may be due to the differences on the metabolism of each antifungal drug in vivo.

  3. Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats

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    Star Khoza

    2017-01-01

    Full Text Available Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p=0.0017 and AST levels (p=0.0008 than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (p<0.0001. The liver enzyme levels suggested that ketoconazole had the highest risk in causing liver injury followed by itraconazole, fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.

  4. Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats.

    Science.gov (United States)

    Khoza, Star; Moyo, Ishmael; Ncube, Denver

    2017-01-01

    Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels ( p = 0.0017) and AST levels ( p = 0.0008) than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment ( p terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.

  5. ACUTE EFFECT OF FLUCONAZOLE, ITRACONAZOLE AND VORICONAZOLE ON BLOOD GLUCOSE IN NORMOGLYCEAMIC & DIABETIC RATS: AN EXPERIMENTAL STUDY

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    Jadhav Amol, Nayak BB, Vakade Kiran P, Sanghishetti Vijay Prasad, Vijay Kumar AN, Vrushali Nibrad, Raul AR

    2015-01-01

    Full Text Available Anti-fungal and antimicrobials are frequently co-prescribed either to manage or treat either the secondary complications or other diseases. Among antifungal drugs Fluconazole, Itraconazole & Voriconazole are most commonly used. The present study was undertaken to further confirm the effect of Voriconazole as well as other antifungal drugs on blood Glucose level. Aim & Objectives: 1. To Study the effect of Fluconazole, Itraconazole & Voriaconazole in Normoglycemic & Diabetic Rats on Blood Glucose. 2. To compare the effects between all drugs. Material & Methodology: Grouping: Animals divided into 8 groups in each group 6 animals. Group 1- 4: Normoglycemic rats, Group 5-8 Diabetic rats (alloxan induced Group 1,5: received vehicle (Normal saline Group 2,6: received Fluconazole (18mg/kg BW, Group 3,7 received Itraconazole (18mg/kg BW Group 4,8 received Voriconazole (18mg/kg BW. The glucose levels were estimated by Glucometer method (Accu-check active at the interval of 0, ½ hr, 1hrs, 2hrs & 4hrs after drug administration. Results: Effect on blood glucose in Normoglycemic Rats: Voriconazole had a significant hypoglycaemic effect which appeared after 1 hr (‘p’ value= 0.0102 of administration & persisted up to 2 hrs (‘p’ value=0.0001. However effect of Voriconzole was found to be declined after 2 hrs. There was no significant change in blood glucose in normoglycemic rats with Fluconazole & Itraconazole. Effect on blood glucose in Diabetic Rats: (Table 2: Voriconazole had a significant hypoglycaemic effect which appeared after 1 hr (‘p’ value=0.013 of administration & persisted up to 2 hrs (‘p’ value=0.001 in acute studies. However effect of Voriconzole was found to be declined after 2 hrs. There was no significant change in blood glucose in diabetic rats with Fluconazole & Itraconazole treated. Conclusion: Itraconazole, Fluconazole can be safely used in diabetic with fungal infections. Voriconazole should be avoided in diabetics to

  6. International and multicenter comparison of EUCAST and CLSI M27-A2 broth microdilution methods for testing susceptibilities of Candida spp. to fluconazole, itraconazole, posaconazole, and voriconazole.

    NARCIS (Netherlands)

    Espinel-Ingroff, A.; Barchiesi, F.; Cuenca-Estrella, M.; Pfaller, M.A.; Rinaldi, M.; Rodriguez-Tudela, J.L.; Verweij, P.E.

    2005-01-01

    The aim of this study was to compare MICs of fluconazole, itraconazole, posaconazole, and voriconazole obtained by the European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI (formerly NCCLS) methods in each of six centers for 15 Candida albicans (5 fluconazole-resistant and 4

  7. In vitro susceptibility of Candida spp. to fluconazole, itraconazole and voriconazole and the correlation between triazoles susceptibility: Results from a five-year study.

    Science.gov (United States)

    Lei, J; Xu, J; Wang, T

    2018-06-01

    Candida spp. is a common cause of invasive fungal disease. The aim of this study was to examine the susceptibility of Candida spp. to fluconazole, itraconazole and voriconazole and explore the correlation between triazoles susceptibility. The antifungal susceptibility in the present study was measured by ATB Fungus 3 method, and the potential relationship was examined by obtaining the correlation of measured minimal inhibitory concentrations (MICs) of Candida spp. isolates. A total of 2099 clinical isolates of Candida spp. from 1441 patients were analyzed. The organisms included 1435 isolates of Candida albicans, 207 isolates of Candida glabrata, 65 isolates of Candida parapsilosis, 31 isolates of Candida krusei, 268 isolates of Candida tropicalis. Voriconazole and itraconazole were more active than fluconazole and against Candida spp. in vitro. The fluconazole, itraconazole and voriconazole MIC 90 (MIC for 90% of the isolates) for all Candida spp. isolates was 4mg/L, 1mg/L and 0.25mg/L, respectively. There was a moderate correlation between the fluconazole MIC s for Candida spp. isolates and this for voriconazole (R 2 =0.475; P<0.01) and itraconazole (R 2 =0.431; P<0.01). Voriconazole MICs for the Candida spp. isolates also correlated with those for itraconazole (R 2 =0.401; P<0.01). These observations suggest that the in vitro susceptibility of Candida spp. to fluconazole, itraconazole and voriconazole exhibits a moderate correlation. Published by Elsevier Masson SAS.

  8. Fluconazole

    Science.gov (United States)

    ... during pregnancy or abnormalities in developing babies when women are exposed to a single 150 mg dose of oral fluconazole to treat ... fluconazole (400-800 mg/day) taken by pregnant women for much longer than a single dose have resulted in reports of abnormalities at ...

  9. Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain

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    Grau Santiago

    2012-04-01

    Full Text Available Abstract Background We evaluated the cost-effectiveness of posaconazole compared with standard azole therapy (SAT; fluconazole or itraconazole for the prevention of invasive fungal infections (IFI and the reduction of overall mortality in high-risk neutropenic patients with acute myelogenous leukaemia (AML or myelodysplastic syndromes (MDS. The perspective was that of the Spanish National Health Service (NHS. Methods A decision-analytic model, based on a randomised phase III trial, was used to predict IFI avoided, life-years saved (LYS, total costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS over patients' lifetime horizon. Data for the analyses included life expectancy, procedures, and costs associated with IFI and the drugs (in euros at November 2009 values which were obtained from the published literature and opinions of an expert committee. A probabilistic sensitivity analysis (PAS was performed. Results Posaconazole was associated with fewer IFI (0.05 versus 0.11, increased LYS (2.52 versus 2.43, and significantly lower costs excluding costs of the underlying condition (€6,121 versus €7,928 per patient relative to SAT. There is an 85% probability that posaconazole is a cost-saving strategy compared to SAT and a 97% probability that the ICER for posaconazole relative to SAT is below the cost per LYS threshold of €30,000 currently accepted in Spain. Conclusions Posaconazole is a cost-saving prophylactic strategy (lower costs and greater efficacy compared with fluconazole or itraconazole in high-risk neutropenic patients.

  10. Effect of 2-Phenylethanol as Antifungal Agent and Common Antifungals (Amphotericin B, Fluconazole, and Itraconazole) on Candida Species Isolated from Chronic and Recurrent Cases of Candidal Vulvovaginitis.

    Science.gov (United States)

    Majdabadi, Niloufar; Falahati, Mehraban; Heidarie-Kohan, Fariba; Farahyar, Shirin; Rahimi-Moghaddam, Parvaneh; Ashrafi-Khozani, Mahtab; Razavi, Tandis; Mohammadnejad, Sina

    2018-04-01

    The antifungal effects of 2-phenylethanol are clearly visible through its intervention in Candida morphogenesis. Chronic and recurrent vulvovaginitis, however, does not respond to this standard experimental therapy; therefore, the study presented in this article investigated the effect of common antifungal drugs (amphotericin B [AMB], fluconazole [FLU], and itraconazole [ITC]), in combination with 2-phenylethanol, on the Candida species isolated from cases of chronic and recurrent vulvovaginitis, thereby allowing the recommendation of a more appropriate treatment option. Forty isolates from patients with chronic and recurrent vaginal candidiasis were investigated in this experimental study. The specimens were examined by direct microscopy, culturing, and PCR to identify the species. The antifungal effects of 2-phenylethanol and conventional drugs, both alone and in combination, were determined in duplicate. Finally, the findings were analyzed. In this study, 40 strains of Candida species were identified, whose agents were Candida albicans (95%) and Candida africana (5%). After 48 h, the minimum inhibitory concentration (MIC) range of the 2-phenylethanol was 800-3,200 μg/mL. Also, in the final study on the MIC levels of common antifungal drugs, AMB (0.42 μg/mL) had the lowest MIC, FLU (40.51 μg/mL) had the highest MIC, and the combination of ITC and 2-phenylethanol had the lowest fractional inhibitory concentration index (FICI) of any of the combinations (FICI range, 0.26-1.03). Combining FLU and ITC with 2-phenylethanol can effectively increase their antifungal effect.

  11. Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates

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    Laura Bedin Denardi

    2015-03-01

    Full Text Available In vitro interaction between tacrolimus (FK506 and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%, followed by that of the combination with ketoconazole (37%, against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata, a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%, itraconazole (73%, voriconazole (63% and fluconazole (60%. The synergisms that we observed in vitro, notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.

  12. Is empiric therapy with fluconazole appropriate for esophageal candidiasis?

    Science.gov (United States)

    Sajith, Kattiparambil Gangadharan; Dutta, Amit Kumar; Sahni, Rani Diana; Esakimuthu, Saritha; Chacko, Ashok

    2014-03-01

    We studied the prevalence of fluconazole resistance in esophageal candidiasis. Patients with suspected esophageal candidiasis during gastroscopy underwent culture of white plaques. Minimum inhibitory concentration (MIC) >64 μg/mL of fluconazole for Candida was indicative of resistance. Sensitivity of itraconazole was tested in a subset of resistant strains. Sixty-five patients were included. Mean (SD) age was 50.03 (13.5) years and 67.7 % were males. Predisposing factors for candidiasis were found in 42 (64.6 %) patients. C. albicans was identified in 64 (97.4 %) patients and C. glabrata in one patient. Fluconazole resistance was seen in 38 (59.4 %) patients with C. albicans and also in the one patient with C. glabrata. All the fluconazole resistant isolates of C. albicans had MIC >128 μg/mL suggesting very high resistance. Twelve patients with fluconazole resistance had itraconazole resistance as well. The study shows a high rate of fluconazole resistance in patients with esophageal candidiasis.

  13. Growth inhibitory action of ebselen on fluconazole-resistant Candida albicans: role of the plasma membrane H+-ATPase.

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    Billack, Blase; Santoro, Michelle; Lau-Cam, Cesar

    2009-06-01

    PMA1 is a yeast gene that codes for the plasma membrane H(+)-ATPase, a protein commonly referred to as Pma1p. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a synthetic selenium-containing compound that has recently been shown to display antimicrobial activity owing to its ability to inhibit Pma1p. Ebselen is able to block the activity of Pma1p not only in opportunistic pathogens such as Cryptococcus neoformans and Candida albicans but also in nonpathogenic yeasts such as Saccharomyces cerevisiae. A series of in vitro studies aimed at evaluating the antifungal activity of ebselen were performed. At low concentrations (ebselen was fungistatic against three strains of S. cerevisiae (IC(50) approximately 3 microM) and one fluconazole-resistant strain of C. albicans (IC(50) approximately 6 microM), and at a high concentration (30 microM) it was fungicidal against C. albicans. Moreover, ebselen was found to inhibit medium acidification by the fluconazole-resistant strain of C. albicans in a concentration-dependent manner. In comparison to currently used antifungal agents represented by azole (itraconazole, ketoconazole, fluconazole) and polyene (amphotericin B) compounds, ebselen was at least 10-fold more potent than fluconazole but less active than the other compounds tested. The present results suggest that the growth inhibitory activity of ebselen toward fluconazole-resistant yeast cells is due, at least in part, to inhibition of Pma1p. Ebselen may also serve as a useful agent in the treatment of infections caused by fluconazole-resistant fungi.

  14. Antifungal Activity of Aqueous Extracts from Ferula Assa foetida Aerial parts on Candida Albicans and its Comparison with Fluconazole in vitro

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    AA Jafari

    2014-09-01

    Results:Concentrations of 8.75 mg/ml aerial parts of Ferula assafoetida completely inhibited the growth of Candida albicans and killed all viable cells (MFC. Concentrations of 0.273 and 4.4 mg/ml Ferula aqueous extracts were also determined as MIC50 and MIC90. In case of Fluconazole, 128 µg/ml concentrationis determined as MFC and 0.5 µg/ml concentration is also known as MIC50. Conclusion:Results of the current study showed that the aqueous extract of Ferula assafoetida aerial parts has inhibitory and candidacidal effect against Candida albicans and further in vivo studies are suggested.

  15. Fluconazol og amning

    DEFF Research Database (Denmark)

    Pedersen, Andreas James Thestrup; Hessellund, Anne; Bergmann, Troels Korshøj

    2016-01-01

    Når lokalbehandling til candidainfektion ikke er nok, er næste valg systemisk behandling. Men hvad, hvis kvinden ammer? Kan systemisk behandling med tablet fluconazol anvendes? Svaret er ja – men langvarig behandling (> 2 uger) bør undgås. Fluconazol vil udskilles i brystmælk, men mængden af...... fluconazol, som barnet derved indtager, er lav....

  16. Longitudinal genotyping of Candida dubliniensis isolates reveals strain maintenance, microevolution, and the emergence of itraconazole resistance.

    LENUS (Irish Health Repository)

    Fleischhacker, M

    2010-05-01

    We investigated the population structure of 208 Candida dubliniensis isolates obtained from 29 patients (25 human immunodeficiency virus [HIV] positive and 4 HIV negative) as part of a longitudinal study. The isolates were identified as C. dubliniensis by arbitrarily primed PCR (AP-PCR) and then genotyped using the Cd25 probe specific for C. dubliniensis. The majority of the isolates (55 of 58) were unique to individual patients, and more than one genotype was recovered from 15 of 29 patients. A total of 21 HIV-positive patients were sampled on more than one occasion (2 to 36 times). Sequential isolates recovered from these patients were all closely related, as demonstrated by hybridization with Cd25 and genotyping by PCR. Six patients were colonized by the same genotype of C. dubliniensis on repeated sampling, while strains exhibiting altered genotypes were recovered from 15 of 21 patients. The majority of these isolates demonstrated minor genetic alterations, i.e., microevolution, while one patient acquired an unrelated strain. The C. dubliniensis strains could not be separated into genetically distinct groups based on patient viral load, CD4 cell count, or oropharyngeal candidosis. However, C. dubliniensis isolates obtained from HIV-positive patients were more closely related than those recovered from HIV-negative patients. Approximately 8% (16 of 194) of isolates exhibited itraconazole resistance. Cross-resistance to fluconazole was only observed in one of these patients. Two patients harboring itraconazole-resistant isolates had not received any previous azole therapy. In conclusion, longitudinal genotyping of C. dubliniensis isolates from HIV-infected patients reveals that isolates from the same patient are generally closely related and may undergo microevolution. In addition, isolates may acquire itraconazole resistance, even in the absence of prior azole therapy.

  17. In Vitro Comparison of Activities of Terbinafine and Itraconazole against Paracoccidioides brasiliensis

    Science.gov (United States)

    Hahn, R. C.; Fontes, C. J. F.; Batista, R. D.; Hamdan, J. S.

    2002-01-01

    In vitro, terbinafine is highly active against a broad spectrum of pathogenic fungi. We evaluated the activities of terbinafine and itraconazole against 31 isolates of Paracoccidioides brasiliensis. The tests were conducted by using a broth macrodilution procedure. MICs, in micrograms per milliliter, were as follows: terbinafine, 0.015 to 1.0 (geometric mean, 0.1188); itraconazole, 0.007 to 0.5 (geometric mean, 0.03165). The usual therapy for paracoccidioidomycosis is sulfonamides, amphotericin B, and azole derivatives (ketoconazole, itraconazole, and fluconazole). In comparison to amphotericin B, azole derivatives allow shorter treatment courses, can be administered orally, and are equally effective. Itraconazole has as high efficacy as ketoconazole, but with superior tolerance. It is the current drug of choice for treatment of paracoccidioidomycosis. The data obtained in this study indicate that terbinafine is active against P. brasiliensis in vitro and suggest that this allylamine can be considered a new option as drug therapy for paracoccidioidomycosis. PMID:12149337

  18. Fluconazole and Pregnancy

    Science.gov (United States)

    ... small increase of birth defects. Can taking fluconazole cause other pregnancy problems? Studies have not found an increase in ... to suggest that a father’s use of fluconazole causes infertility or birth ... to a pregnancy. For more information, please see the MotherToBaby fact ...

  19. A Case Report of Penile Infection Caused by Fluconazole- and Terbinafine-Resistant Candida albicans.

    Science.gov (United States)

    Hu, Yongxuan; Hu, Yanqing; Lu, Yan; Huang, Shiyun; Liu, Kangxing; Han, Xue; Mao, Zuhao; Wu, Zhong; Zhou, Xianyi

    2017-04-01

    Candida albicans is the most common pathogen that causes balanoposthitis. It often causes recurrence of symptoms probably due to its antifungal resistance. A significant number of balanitis Candida albicans isolates are resistant to azole and terbinafine antifungal agents in vitro. However, balanoposthitis caused by fluconazole- and terbinafine-resistant Candida albicans has rarely been reported. Here, we describe a case of a recurrent penile infection caused by fluconazole- and terbinafine-resistant Candida albicans, as well as the treatments administered to this patient. The isolate from the patient was tested for drug susceptibility in vitro. It was sensitive to itraconazole, voriconazole, clotrimazole and amphotericin B, but not to terbinafine and fluconazole. Thus, oral itraconazole was administrated to this patient with resistant Candida albicans penile infection. The symptoms were improved, and mycological examination result was negative. Follow-up treatment of this patient for 3 months showed no recurrence.

  20. Clinical effectiveness of posaconazole versus fluconazole as antifungal prophylaxis in hematology–oncology patients: a retrospective cohort study

    International Nuclear Information System (INIS)

    Kung, Hsiang-Chi; Johnson, Melissa D; Drew, Richard H; Saha-Chaudhuri, Paramita; Perfect, John R

    2014-01-01

    In preventing invasive fungal disease (IFD) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), clinical trials demonstrated efficacy of posaconazole over fluconazole and itraconazole. However, effectiveness of posaconazole has not been investigated in the United States in real-world setting outside the environment of controlled clinical trial. We performed a single-center, retrospective cohort study of 130 evaluable patients ≥18 years of age admitted to Duke University Hospital between 2004 and 2010 who received either posaconazole or fluconazole as prophylaxis during first induction or first reinduction chemotherapy for AML or MDS. The primary endpoint was possible, probable, or definite breakthrough IFD. Baseline characteristics were well balanced between groups, except that posaconazole recipients received reinduction chemotherapy and cytarabine more frequently. IFD occurred in 17/65 (27.0%) in the fluconazole group and in 6/65 (9.2%) in the posaconazole group (P = 0.012). Definite/probable IFDs occurred in 7 (10.8%) and 0 patients (0%), respectively (P = 0.0013). In multivariate analysis, fluconazole prophylaxis and duration of neutropenia were predictors of IFD. Mortality was similar between groups. This study demonstrates superior effectiveness of posaconazole over fluconazole as prophylaxis of IFD in AML and MDS patients. Such superiority did not translate to reductions in 100-day all-cause mortality

  1. Oral fluconazole in tinea versicolor

    Directory of Open Access Journals (Sweden)

    Sankara Rao I

    1997-01-01

    Full Text Available 25 patients with extensive tinea versicolor were treated with single oral dose of 400 mg of fluconazole. 25 patients returned for follow-up. Follow-up at 3 weeks, 6 weeks and 8 weeks showed 100% clinical cure rate and 92% mycological cure rate. No significant side effects were noticed. The majority of patients found the treatment effective, safe and convenient.

  2. Susceptibility testing of Cryptococcus diffluens against amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole

    NARCIS (Netherlands)

    Kantarcioglu, A.S.; Boekhout, T.; Yucel, A.; Altas, K.

    2009-01-01

    Cryptococcus diffluens is a recently re-established species that shares several phenotypic features with Cryptococcus neoformans. We evaluated the application of the Clinical Laboratory Standards Institute (CLSI, formerly NCCLS) macro- and microbroth dilution methods and the E-test agar diffusion

  3. Skin rash during treatment with generic itraconazole.

    Science.gov (United States)

    De Vuono, Antonio; Palleria, Caterina; Scicchitano, Francesca; Squillace, Aida; De Sarro, Giovambattista; Gallelli, Luca

    2014-04-01

    Generic drugs have the same active substance, the same pharmaceutical form, the same therapeutic indications and a similar bioequivalence with the reference medicinal product (branded). Although a similar efficacy is postulated, some cases of clinical inefficacy during treatment with generic formulations have been reported. In this case, we describe a woman with onychomycosis that developed a skin rash during treatment with a generic formulation of itraconazole. Drug administration and its re-challenge confirmed the association between itraconazole and skin rash. Both Naranjo probability scale and World Health Organization causality assessment scale documented a probable association between generic-itraconazole and skin rash. The switch from generic formulation to brand one induced an improvement of symptoms. Since we are unable to evaluate the role of each excipient in the development of skin rash, we cannot rule out their involvement. However, more data are necessary to better define the similarities or differences between branded and generic formulations.

  4. Itraconazole-resistant Candida auris with phospholipase, proteinase and hemolysin activity from a case of vulvovaginitis.

    Science.gov (United States)

    Kumar, Dharmendra; Banerjee, Tuhina; Pratap, Chandra Bhan; Tilak, Ragini

    2015-04-15

    Since the emergence of pathogenic non-albicans Candida species, a number of new isolates have been added to the list. One such unusual species is Candida auris (C. auris), recently isolated and studied in few reports. In this study, a case of vulvovaginitis caused by Candida auris incidentally identified by molecular methods using internal transcribed spacer polymerase chain reaction (ITS PCR) is described. Antifungal susceptibility testing revealed the isolate to be resistant to itraconazole (MIC ≥ 2 µg/ml) and expressed important virulence factors including phospholipase, proteinase and hemolysin activity. The patient was successfully treated with oral fluconazole and did not have any invasive fungemia. Very few cases of this emerging pathogen have been reported. However, its isolation from clinical specimens reveals the significance of non-albicans candida species over C. albicans and the diversity of Candida spp causing infections.

  5. Skin rash during treatment with generic itraconazole

    OpenAIRE

    De Vuono, Antonio; Palleria, Caterina; Scicchitano, Francesca; Squillace, Aida; De Sarro, Giovambattista; Gallelli, Luca

    2014-01-01

    Generic drugs have the same active substance, the same pharmaceutical form, the same therapeutic indications and a similar bioequivalence with the reference medicinal product (branded). Although a similar efficacy is postulated, some cases of clinical inefficacy during treatment with generic formulations have been reported. In this case, we describe a woman with onychomycosis that developed a skin rash during treatment with a generic formulation of itraconazole. Drug administration and its re...

  6. Failure of itraconazole to prevent T-helper type 2 cell immune deviation: Implications for chronic rhinosinusitis.

    Science.gov (United States)

    Kennedy, Joshua L; Steinke, John W; Liu, Lixia; Negri, Julie; Borish, Larry; Payne, Spencer C

    2016-11-01

    T-helper (Th) type 2 cell inflammation is the hallmark of several disease processes, including asthma, atopic dermatitis, and some forms of chronic rhinosinusitis. Itraconazole has been used as both an antifungal and an anti-inflammatory agent, with some success in many of these diseases, in part, by altering Th2 cytokine expression by T cells. It is not known whether this merely reflects inhibition of established Th2-like cells or the inhibition of differentiation of naive T cells into Th2-like cells. To evaluate the role of itraconazole in the differentiation of naive T cells during activation. Naive CD45RA+ T cells were isolated from peripheral blood mononuclear cells from healthy volunteers. Th1 and Th2 type cells were differentiated in the presence of varying concentrations of itraconazole. After stimulation with anti-CD3 and anti-CD28 beads, carboxyfluorescein succinimidyl ester dilution was performed to evaluate proliferation and intracellular cytokine staining for interleukin (IL) 4 and interferon (IFN) gamma within proliferating T cells was measured along with enzyme-linked immunosorbent assay for secreted IL-5, IL-13, and IFN gamma. Itraconazole had no effect on proliferation of unbiased, Th1, or Th2 cells. Similarly, there was no effect of itraconazole on either intracellular cytokine staining of IL-4 and IFN gamma or secreted cytokine expression of IFN gamma, IL-5, and IL-13 in any of the cell populations. Itraconazole did not alter the ability of naive T cells to proliferate or secrete cytokines under Th1 or Th2 deviating conditions in vitro. As such, reported inhibition of Th2-like lymphocyte function by itraconazole reflected action on mature effector cells and may have underscored why antifungal treatment failed in many clinical trials of eosinophilic chronic rhinosinusitis.

  7. Fluconazole inhibits human adrenocortical steroidogenesis in vitro

    NARCIS (Netherlands)

    R. van der Pas (Rob); L.J. Hofland (Leo); J. Hofland (Johannes); A.E. Taylor (A.); W. Arlt (Wiebke); J. Steenbergen (Jacobie); P.M. van Koetsveld (Peter); W.W. de Herder (Wouter); F.H. de Jong (Frank); R.A. Feelders (Richard)

    2012-01-01

    textabstractThe antifungal agent ketoconazole is often used to suppress cortisol production in patients with Cushing's syndrome (CS). However, ketoconazole has serious side effects and is hepatotoxic. Here, the in vitro effects of ketoconazole and fluconazole, which might be less toxic, on human

  8. Successful Treatment of Fluconazole-Resistant Oropharyngeal Candidiasis by a Combination of Fluconazole and Terbinafine

    Science.gov (United States)

    Ghannoum, Mahmoud A.; Elewski, Boni

    1999-01-01

    Increasing incidence of resistance to conventional antifungal therapy has demanded that novel therapies be introduced. Recent in vitro studies have shown that combinations involving azoles and allylamines may be effective in inhibiting fluconazole-resistant fungi. In this report, we describe the case of a 39-year-old woman who presented with white patches on her buccal mucosa, tongue, and palate with a bright erythematous erosive base. A fungal culture revealed Candida albicans. The patient failed to respond to the initially prescribed fluconazole therapy. Failure of therapy can be attributed to a developed resistance to fluconazole from the patient’s intermittent use of this antifungal agent at varying dosages for the preceding 2 years due to a diagnosis of onychomycosis. In vitro testing of the culture from the patient showed elevated MICs of fluconazole, itraconzole, and terbinafine (MICs were 32, 0.5, and 64 μg/ml, respectively). Our goal was to combine therapies of fluconazole and terbinafine in an attempt to clear the fungal infection. Impressively, this combination resulted in the clearing of the clinical symptoms and the patient has successfully been asymptomatic for more than 12 months posttreatment. PMID:10548586

  9. Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats.

    Directory of Open Access Journals (Sweden)

    Jeong Hun Bae

    Full Text Available Choroidal neovascularization (CNV is a major cause of severe visual loss in patients with age-related macular degeneration (AMD. Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS as controls. On day 14 after laser induction, fluorescein angiography (FA was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2 mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA. Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume. Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006. Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001. Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or

  10. Fixed drug eruption resulting from fluconazole use: a case report

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    Tavallaee Mahkam

    2009-07-01

    Full Text Available Abstract Introduction Fluconazole is a widely used antifungal agent with a possible side effect of fixed drug eruption. However, this adverse drug effect is absent from the reported list of possible side effects of fluconazole. We are presenting a rare case in our report. Case presentation A 25-year-old Iranian woman developed fixed drug eruptions on different sites of her body after taking five doses of fluconazole to treat vaginal candidiasis. A positive patch test, positive oral challenge test and skin biopsy were all found to be consistent with fixed drug eruption. Conclusion Fluconazole is a widely prescribed drug, used mainly to treat candidiasis. Fixed drug eruption as a possible side effect of Fluconazole is not well known and thus, the lesions may be misdiagnosed and mistreated. Based on our findings, which are consistent with a number of other practitioners, we recommend adding fixed drug eruption to the list of possible side effects of fluconazole.

  11. Fluconazole use and safety in the nursery.

    Science.gov (United States)

    Castagnola, E; Jacqz-Aigrain, E; Kaguelidou, F; Maragliano, R; Stronati, M; Rizzollo, S; Farina, D; Manzoni, P

    2012-05-01

    Fluconazole is a triazole antifungal agent that is widely used in the nursery. It is available in both intravenous and oral formulation, and is active against most of the fungal pathogens that require treatment when retrieved from culture samples in neonatal intensive care units. Although clinical use has been wide for over 15 years, there have been small safety and efficacy studies completed in young infants. Randomised clinical trials assessing effectiveness of this agent in prevention of systemic fungal infections in neonates have been published in the last decade, and one large additional randomised study has been recently completed. Nevertheless, a certain degree of uncertainty still exists regarding the kinetics and appropriate dosing of this agent in premature and term infants, as well as regarding safety. Areas of poignant debate include the feasibility of loading dose strategies, appropriate dosages in the early days of life in the different subgroups of preterm infants, and long-term safety of fluconazole administered in prophylaxis during the first weeks of life in extremely premature infants. This paper reviews the most recent evidence on fluconazole and its role in the NICU settings. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Verstoring van de pilcyclus tijdens het gelijktijdig gebruik van itraconazol en orale anticonceptiva

    NARCIS (Netherlands)

    van Puijenbroek, E P; Feenstra, J; Meyboom, R H

    1998-01-01

    Since the introduction of itraconazole in the Netherlands, the Netherlands Pharmacovigilance Foundation LAREB and the Inspectorate for Health Care received 15 reports of pill cycle disturbances and one of pregnancy occurring during simultaneous use of itraconazole and oral contraceptives. Twelve

  13. Comparison of Compounded, Generic, and Innovator-Formulated Itraconazole in Dogs and Cats.

    Science.gov (United States)

    Renschler, Janelle; Albers, Amanda; Sinclair-Mackling, Hanna; Wheat, Lawrence Joseph

    2018-05-14

    The triazole antifungal itraconazole may be cost prohibitive in brand name form; therefore, compounded and generic products are often used as alternatives. Itraconazole blood concentrations have not been studied in clinical patients receiving these formulations. Itraconazole bioassay was performed on serum/plasma from 95 dogs and 20 cats receiving itraconazole (compounded from bulk powder, generic pelletized, or brand name) for systemic mycosis treatment. Mean itraconazole concentration was lower in the compounded group (n = 42) as compared with the generic (n = 40) or brand name (n = 33) groups (0.5 µg/mL versus 8.3 µg/mL and 6.5 µg/mL, respectively; P 10 µg/mL; 37.5 and 24%, respectively). Compounded itraconazole should be avoided, but generic itraconazole appears to serve as a reasonable alternative to brand name itraconazole. Therapeutic drug monitoring may be beneficial in all cases.

  14. Oral itraconazole for the treatment of severe seborrhoeic dermatitis

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    Jayasri Das

    2011-01-01

    Full Text Available Background : Seborrheic dermatitis (SD is an inflammatory skin disorder in which colonies of Malassezia furfur have been found in affected areas. Aim: The aim of this study was to evaluate the efficacy of itraconazole in the treatment of severe SD. Materials and Methods: Itraconazole was given to 30 patients of SD in a dose of 100 mg twice daily for 1 week followed by 200 mg/day for first 2 days of the following 2 months. The response was noted on day 15, 30, 60, and 90. The clinical response was graded as markedly effective, effective, or ineffective. Results: Clinical improvement (evaluated as markedly effective or effective was observed in 83.3% cases. Conclusion : The anti-inflammatory activity of oral itraconazole suggests that it should be the first-line therapy in severe SD.

  15. Triclosan antagonizes fluconazole activity against Candida albicans.

    LENUS (Irish Health Repository)

    Higgins, J

    2012-01-01

    Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg\\/L. However, at subinhibitory concentrations (0.5-2 mg\\/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Δ and cdr2Δ strains. Triclosan did not affect fluconazole uptake or alter total membrane sterol content, but did induce the expression of FAS1 and FAS2, indicating that its mode of action may involve inhibition of fatty acid synthesis, as it does in prokaryotes. However, FAS2 mutants did not exhibit increased susceptibility to triclosan, and overexpression of both FAS1 and FAS2 alleles did not alter triclosan susceptibility. Unexpectedly, the antagonistic effect was specific for C. albicans under hypha-inducing conditions and was absent in the non-filamentous efg1Δ strain. This antagonism may be due to the membranotropic activity of triclosan and the unique composition of hyphal membranes.

  16. Design, synthesis, and evaluation of caffeic acid amides as synergists to sensitize fluconazole-resistant Candida albicans to fluconazole.

    Science.gov (United States)

    Dai, Li; Zang, Chengxu; Tian, Shujuan; Liu, Wei; Tan, Shanlun; Cai, Zhan; Ni, Tingjunhong; An, Maomao; Li, Ran; Gao, Yue; Zhang, Dazhi; Jiang, Yuanying

    2015-01-01

    A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 μg/ml, decreased the MIC₈₀ of fluconazole from 128.0 μg/ml to 1.0-0.5 μg/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides.

  17. Use of Pinus sylvestris L. (Pinaceae), Origanum vulgare L. (Lamiaceae), and Thymus vulgaris L. (Lamiaceae) essential oils and their main components to enhance itraconazole activity against azole susceptible/not-susceptible Cryptococcus neoformans strains.

    Science.gov (United States)

    Scalas, Daniela; Mandras, Narcisa; Roana, Janira; Tardugno, Roberta; Cuffini, Anna Maria; Ghisetti, Valeria; Benvenuti, Stefania; Tullio, Vivian

    2018-05-03

    Cryptococcal infections, besides being a problem for immunocompromised patients, are occasionally being a problem for immunocompetent patients. In addition, the lower susceptibility of this yeast to azoles is a growing problem in health care. To date, there are very few molecules with any activity towards Cryptococcus neoformans, leading to heightened interest in finding new alternatives or adjuvants to conventional drugs for the treatment of mycosis caused by this yeast. Since the essential oils (EOs) are considered as a potential rich source of bioactive antimicrobial compounds, we evaluated the antifungal activity of Origanum vulgare (oregano), Pinus sylvestris (pine), and Thymus vulgaris (thyme red) EOs, and their components (α-pinene, carvacrol, thymol) compared with fluconazole, itraconazole, and voriconazole, against C.neoformans clinical strains. Then, we investigated the effect of EOs and components in combination with itraconazole. EO composition was analysed by Gas chromatography-mass spectrometry (GC-MS). A broth microdilution method was used to evaluate the susceptibility of C.neoformans to azoles, EOs and components. Checkerboard tests, isobolograms and time-kill assays were carried out for combination studies. Six C.neoformans isolates were susceptible to azoles, while one C.neoformans exhibited a reduced susceptibility to all tested azole drugs. All EOs exerted a good inhibitory activity against all C.neoformans strains. Pine EO was the most effective. Among components, thymol exerted the most remarkable activity. By checkerboard testing and isobolographic analysis, combinations of itraconazole with oregano, pine, or thyme EOs, and carvacrol were found to be synergistic (FICI≤0.5) against azole susceptible C.neoformans. Regarding the azole not susceptible C.neoformans strain, the synergistic effect with itraconazole was observed with thyme EO (chemotype: thymol 26.52%; carvacrol 7.85%), and carvacrol. Time-kill assays confirmed the synergistic

  18. Disseminated cryptococcosis and fluconazole resistant oral candidiasis in a patient with acquired immunodeficiency syndrome (AIDS).

    Science.gov (United States)

    Kothavade, Rajendra J; Oberai, Chetan M; Valand, Arvind G; Panthaki, Mehroo H

    2010-10-28

    Disseminated cryptococcosis and recurrent oral candidiasis was presented in a-heterosexual AIDS patient. Candida tropicalis (C.tropicalis) was isolated from the oral pseudomembranous plaques and Cryptococcus neoformans (C. neoformans) was isolated from maculopapular lesions on body parts (face, hands and chest) and body fluids (urine, expectorated sputum, and cerebrospinal fluid). In vitro drug susceptibility testing on the yeast isolates demonstrated resistance to fluconazole acquired by C. tropicalis which was a suggestive possible root cause of recurrent oral candidiasis in this patient.

  19. Disseminated primary cutaneous histoplasmosis successfully treated with itraconazole

    Directory of Open Access Journals (Sweden)

    Singhi M

    2003-11-01

    Full Text Available A 60-year-old immunocompetent lady with disseminated primary cutaneous histoplasmosis is reported. Histology showed a granulomatous skin infiltrate with numerous intracellular PAS positive rounded yeast cells within macrophages. Culture on Sabouraud′s dextrose agar yielded a typical cottony white colony characteristic of Histoplasma capsulatum. Treatment with itraconazole showed an excellent response.

  20. In Vitro Comparison of Terbinafine and Itraconazole against Penicillium marneffei

    Science.gov (United States)

    McGinnis, Michael R.; Nordoff, Nicole G.; Ryder, Neil S.; Nunn, Gary B.

    2000-01-01

    We evaluated terbinafine and itraconazole against 30 isolates of Penicillium marneffei using a modification of the National Committee for Clinical Laboratory Standards broth macrodilution MIC testing protocol for yeasts. The minimal fungicidal concentration (MFC) was determined by plating 100 μl from each MIC drug dilution having no growth onto Sabouraud glucose agar incubated at 30°C. The MFC was the dilution at which growth was absent at 72 h of incubation. The MICs, in micrograms per milliliter, were as follows: terbinafine, 0.03 to 1.0 (geometric mean titer, 0.09); itraconazole, 0.03 to 0.5 (geometric mean titer, 0.04). The MFCs, in micrograms per milliliter, were as follows: terbinafine, 0.03 to 8 (geometric mean titer, 2.60); itraconazole, 0.03 to 8 (geometric mean titer, 2.45). Primary fungicidal activity (MFC within 2 dilutions of MIC) was observed with terbinafine in eight isolates and with itraconazole in four isolates. The data indicate that terbinafine is active against P. marneffei in vitro and may have a previously unrealized role in the management of infections caused by this fungus. PMID:10770792

  1. Fluconazole Therapy in Febrile Granulocytopenic Cancer Patients

    International Nuclear Information System (INIS)

    Faris, L.; Al-Shaarawy, I.; Abd Al-Karim, K.; Iskandar, N.A.

    2004-01-01

    This study was conducted to evaluate the efficacy and safety of fluconazole oral or IV solution in the treatment of systemic fungal infections. Thirty-two febrile granulocytopenic patients with hematologic malignancies were included. They were 21 males (65.6%) and 11 females (34.4%). Their ages ranged between 21.5 to 72 years with a mean age of 44.8 ±13.1 years. Primary diagnosis was Lymphoma in 28 patients (87.5%), Acute Lymphocytic Leukemia in 3 patients (9.4%) and Acute Myeloid Leukemia in 1 patient (3.1%). Duration of fever and neutropenia ranged between 3-20 days and 3-50 days respectively. Fever of unknown origin (FUO)was reported in 25 patients (78.1%). Following initial assessment all patients received broad-spectrum antibiotics. Persistence of fever and neutropenia for 4 days while on broad-spectrum antibiotics necessitated addition of fluconaz-ole. At baseline visit body temperature and leucocyte count measures ranged between 38.2-40.1 degree with a mean of 39.3 degree 110-1800/cm 3 with a mean of 1080/cm 3 respectively. Besides, clinical picture of infection included most commonly cough and expectoration, and moniliasis. Mycological cultures showed positive fungal growth of all collected specimens (100%). All patients were assigned to receive 400-800 mg of fluconazole once daily either orally or parentally. Marked clinical improvement in signs and symptoms of infection was achieved as early as second visit (day-4). Significant reduction in number of growing colonies of fungi was reported by the first follow-up mycological culture (day-8). At final visit (day-14-21) complete clinical cure was achieved in 26 patients (81.3%) and improvement in 4 patients (18.7%). Mycological cultures showed complete eradication of growing colonies in 21 patients (70%) and significant reduction in number of growing colonies in 9 patients (30%). Duration of therapy ranged between 14 and 21 days with a mean of 15 days

  2. Antifungal Effects of Gold Nanoparticles Conjugated Fluconazole against Fluconazole Resistant Strains of Candida albicans Isolated From Patients with Chronic Vulvovaginitis

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    Mehrdad Memarian

    2016-09-01

    Full Text Available Background and Objectives: A number of women with volvuvaginal candidiasis suffer from certain chronic and recurrent types of this infection that affect their quality of life. Meanwhile, increased use of antifungal drugs, especially azoles, for treatment of chronic candidiasis is an important factor for incidence of drug resistance in Candida isolates from patients with vulvovaginal candidiasis. The aim of this study was to investigate anticandidal effects of gold nanoparticles conjugated fluconazole to develop better drugs for treatment of patients with candidal vaginitis, especially its chronic type. Methods: After collection of 300 vaginal swab specimens and culture and isolation of primary colonies and determination of Candida species, fluconazole resistant strains of Candida albicans were detected using disc diffusion. Finally, antifungal effects of gold nanoparticles conjugated fluconazole and fluconazole were compared by broth microdilution. Results: Only one fluconazole resistant strain of C. albicans was isolated from patients (MIC=64µg/ml. The results obtained from drug susceptibility test showed that this strain was sensitive to gold nanoparticles conjugated fluconazole (MIC=2µg/ml. Conclusion: Given the optimal anticandidal effects of gold nanoparticles conjugated fluconazole on resistant strains of C. albicans, a suitable compound with great anticandidal properties may be achieved in the future.

  3. Confluent And Reticulated Papillomatosis : Treatment Response to Fluconazole

    Directory of Open Access Journals (Sweden)

    Ravikumar B C

    1997-01-01

    Full Text Available A case of confluent and reticulated papillomatosis with classical flexual pigmented papules distributed in reticular pattern is described. Patient responded well to a one- month course of Fluconazole therapy.

  4. Thermoanalytical study of polymorphic transformation in Fluconazole drug

    International Nuclear Information System (INIS)

    Desai, S.R.; Shaikh, M.M.; Dharwadkar, S.R.

    2003-01-01

    Polymorphic transformation in Fluconazole (I) drug has been studied employing differential scanning calorimetry (DSC), X-ray diffraction and FT-IR techniques. Fluconazole (I) exhibited the sharp melting point at 138.4 deg. C. Considerable under cooling was, however, observed for the drug during cooling. No indication of freezing of molten Fluconazole (I) was evident in the DSC curve recorded up to a temperature of 25 deg. C in the cooling cycle. Reheating of the sample obtained after cooling, produced the DSC pattern much different compared to that obtained in the first heating and consisted of a sharp exothermic peak beginning at 81 deg. C preceding the twin endothermic peak with an onset temperature of 135.3 deg. C. In addition to these two peaks, a small endothermic peak was also observed around 31 deg. C, which could be attributed to a glass transition with an associated relaxation. The precise glass transition temperature derived from the data collected from six different independent experiments was found to be (31.67±0.13) deg. C. X-ray diffraction pattern of the Fluconazole (I) indicated that the as received sample was crystalline. The molten Fluconazole on cooling, however, produced a glassy amorphous mass. The amorphous product on heating to temperature >81 deg. C transformed to Fluconazole (II) which subsequently changed to Fluconazole (I) prior to melting. The split endothermic peak beginning at 135.3 deg. C recorded for the solidified Fluconazole sample is consistent with the observations made by X-ray diffraction. The observations made by employing DSC and X-ray diffraction were corroborated by FT-IR data on the samples isolated at different stages in the experiments

  5. Thermoanalytical study of polymorphic transformation in Fluconazole drug

    Energy Technology Data Exchange (ETDEWEB)

    Desai, S.R.; Shaikh, M.M.; Dharwadkar, S.R

    2003-03-24

    Polymorphic transformation in Fluconazole (I) drug has been studied employing differential scanning calorimetry (DSC), X-ray diffraction and FT-IR techniques. Fluconazole (I) exhibited the sharp melting point at 138.4 deg. C. Considerable under cooling was, however, observed for the drug during cooling. No indication of freezing of molten Fluconazole (I) was evident in the DSC curve recorded up to a temperature of 25 deg. C in the cooling cycle. Reheating of the sample obtained after cooling, produced the DSC pattern much different compared to that obtained in the first heating and consisted of a sharp exothermic peak beginning at 81 deg. C preceding the twin endothermic peak with an onset temperature of 135.3 deg. C. In addition to these two peaks, a small endothermic peak was also observed around 31 deg. C, which could be attributed to a glass transition with an associated relaxation. The precise glass transition temperature derived from the data collected from six different independent experiments was found to be (31.67{+-}0.13) deg. C. X-ray diffraction pattern of the Fluconazole (I) indicated that the as received sample was crystalline. The molten Fluconazole on cooling, however, produced a glassy amorphous mass. The amorphous product on heating to temperature >81 deg. C transformed to Fluconazole (II) which subsequently changed to Fluconazole (I) prior to melting. The split endothermic peak beginning at 135.3 deg. C recorded for the solidified Fluconazole sample is consistent with the observations made by X-ray diffraction. The observations made by employing DSC and X-ray diffraction were corroborated by FT-IR data on the samples isolated at different stages in the experiments.

  6. Fluconazole prophylaxis in preterm infants: a systematic review.

    Science.gov (United States)

    Rios, Juliana Ferreira da Silva; Camargos, Paulo Augusto Moreira; Corrêa, Luísa Petri; Romanelli, Roberta Maia de Castro

    This article aims to review the use of antifungal prophylaxis with intravenous fluconazole in premature newborns and the occurrence of Invasive Candidiasis. This is a systematic review with search at databases: PubMed, Capes Portal, Virtual Health Library (BVS - Biblioteca Virtual em Saúde)/Lilacs, Scopus and Cochrane. The keywords used were: "Antifungal", "Candida" "Fluconazole prophylaxis" and "Preterm infants". Invasive Candidiasis was evaluated in all the twelve items. In eleven of them, there was a statistically significant difference between the groups receiving prophylactic fluconazole, with lower frequency of Invasive Candidiasis, compared to placebo or no prophylaxis group. Colonization by Candida species was also evaluated in five studies; four of them presented statistically lower proportion of colonization in patients with Fluconazole prophylaxis, compared to placebo or no drugs. In one study, there was a significant difference, favoring the use of fluconazole, and reduction of death. Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  7. Assessment of the quality of compounded fluconazole capsules marketed in the region of Araraquara (SP, Brazil

    Directory of Open Access Journals (Sweden)

    Josilene Chaves Ruela Corrêa

    2014-04-01

    Full Text Available The quality control of drugs has an important role in public health, in ensuring the efficacy and safety of medicines. In the public health system, compounding pharmacies play a vital part. They provide medicines tailored to the individual patient, for example dermatological products and specific doses for children. Unfortunately, many cases of compounded products falling below the minimum quality standard have been reported in Brazil. In this study, the quality of compounded 150 mg fluconazole capsules was assessed and the results were compared with values stipulated in the Brazilian pharmacopoeia. The results suggest that, while it is certainly possible to prepare products meeting pharmacopoeial specifications, there are pharmacies where the quality control is deficient or nonexistent. Fluconazole is an important drug in combatting fungal infections. The use of fluconazole in dosage forms manufactured without high standards of quality control is strongly linked to treatment failure and cases of intoxication, as well as the emergence of resistant microorganisms. This highlights the urgent need for process improvement in compounding pharmacies. There are validated methods that can be successfully employed for routine quality control analysis that can be implemented by any compounding pharmacy.

  8. Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis

    Directory of Open Access Journals (Sweden)

    Jan Susilo

    2011-08-01

    Full Text Available Background: Vaginal candidiasis (VC is one of the most common fungal diseases. Candida albicans is the most common causative fungus and has been isolated from more than 80% of specimens obtained from women with VC. Ketoconazole is the first orally active antifungal, the dosage for VC is 200 mg twice daily for 5 days. Fluconazole is the newer oral antifungal, its dosage for VC is a single oral dose of 150 mg. Since fluconazole 150 mg is considerably expensive, a single dose of 100 mg ketoconazole and 40 mg fluconazole in combination has been tested for the treatment of VC. The results showed that from 11 women with confirmed VC, 1-2 weeks after drug administration, the mycological culture was negative in 8 women, positive in 1 woman, and 2 woman lost to follow-up. This promising result led to the present study with the objective to confirm the efficacy and safety of the above combination in a formal clinical trial.Methods: A total of 165 female patients, aged 18 years or older, with the diagnosis of VC from clinical symptoms (pruritus or burning or excessive discharge and positive microscopic smear (pseudohyphae and/or yeast cells were randomized to receive a single dose of either keto-fluco combination (n = 85 or fluconazole (n = 80, and returnedfor follow-up visit on day 8.Results: Among these patients, 39 patients had negative baseline culture, leaving 126 patients eligible for efficacy evaluation. The mycological eradication in the keto-fluco group was 74.5% (41 patients from a total of 55 patients with available mycological culture, while that in the fluconazole group was 70.2% (40 patients from 57 patients with available culture and this difference was not significant. The clinical favorable response (clinical cure and clinical improvement in the keto-fluco arm (n = 60 was 98.3%, while that in the fluconazole group (n = 66 was 100%. Adverse events were found in 5 patients, 3 patients in the keto-fluco group (3/85 = 3.5% and 2

  9. A meta-analysis comparing efficacy of continuous terbinafine with intermittent itraconazole for toenail onychomycosis

    Directory of Open Access Journals (Sweden)

    Trivedi N

    2010-01-01

    Full Text Available Background: Toenail onychomycosis is a challenge for clinicians to treat. While both Itraconazole and terbinafine have proven to be effective against onychomycosis, very little is known about their comparative efficacy in achieving mycological and clinical cure. Aim: The purpose of this meta-analysis is to compare the efficacy of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis. Material and Methods: all RCTs comparing continuous terbinafine with intermittent itraconazole were identified from PUBMED and BIDS electronic database. Results: analysis of total eight trials including 1181 patients state that treatment with continuous terbinafine is more likely to produce mycological and clinical cure compared to intermittent itraconazole with odds ratio 2.3(95% CI, 1.7 to 3.0 P< 0.0001 Conclusion: though both itraconazole and terbinafine are well tolerated and highly effective drugs, continuous terbinafine is more effective than intermittent itraconazole at achieving mycological cure of toenail onychomycosis

  10. Fluconazole-Warfarin Interaction: A case report with deadly consequences

    Directory of Open Access Journals (Sweden)

    Elliot V Hersh

    2017-06-01

    Full Text Available Adverse drug-drug interactions are more common in the elderly because of the commonality of polypharmacy. When one of the interacting drugs has a low therapeutic index, the consequences can be life-threatening or fatal. This case describes a fatal cerebral haemorrhage in an 80-year old male on stable doses of warfarin prescribed by his cardiologist, who was prescribed fluconazole 200mg, once daily, for 14 days by an oral and maxillofacial surgeon to treat an intraoral fungal infection. The oral surgeon was aware that the patient was on warfarin and his INR two days prior to the appointment was 2.4. While a drug interaction alert was sent to the patient’s primary care family physician regarding fluconazole and the simvastatin she had been prescribing, the interaction was not reviewed by her for another 9- days. She then informed the patient that “it was fine” to finish the fluconazole. However, this phone conversation prompted the patient to discontinue the fluconazole after 8 doses. Two days later, the patient was confused and driving his car erratically. His son rushed him to the hospital where a CAT scan revealed a large frontal intraparenchymal haemorrhage. His INR was a 9.6. This event illustrates that this well-documented adverse drug interaction needs to be better highlighted in dental and medical training. Warfarin’s primary metabolic pathway involves the cytochrome P-450 2C9 isoform and fluconazole is a strong inhibitor of this enzyme, with the potential outcome being excessive warfarin blood levels. Frequent INR monitoring with potential warfarin dosage adjustments downward if fluconazole is prescribed, or the complete avoidance of fluconazole is recommended in patients taking warfarin. The importance of communication and coordinated care between different health care providers cannot be overstated.

  11. Fluconazole resistance in Candida species: a current perspective

    Directory of Open Access Journals (Sweden)

    Berkow EL

    2017-07-01

    Full Text Available Elizabeth L Berkow, Shawn R Lockhart Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract: Candida albicans and the emerging non-albicans Candida spp. have significant clinical relevance among many patient populations. Current treatment guidelines include fluconazole as a primary therapeutic option for the treatment of these infections, but it is only fungistatic against Candida spp. and both inherent and acquired resistance to fluconazole have been reported. Such mechanisms of resistance include increased drug efflux, alteration or increase in the drug target, and development of compensatory pathways for producing the target sterol, ergosterol. While many mechanisms of resistance observed in C. albicans are also found in the non-albicans species, there are also important and unexpected differences between species. Furthermore, mechanisms of fluconazole resistance in emerging Candida spp., including the global health threat Candida auris, are largely unknown. In order to preserve the utility of one of our fundamental antifungal drugs, fluconazole, it is essential that we fully appreciate the manner by which Candida spp. manifest resistance to it. Keywords: Candida, fluconazole resistance, ERG11, drug efflux, ergosterol

  12. In vitro synergism of simvastatin and fluconazole against Candida species

    Directory of Open Access Journals (Sweden)

    Everardo Albuquerque Menezes

    2012-08-01

    Full Text Available Systemic fungal infections are responsible for high mortality rates. Several species of fungi may be involved, but Candida spp. is the most prevalent. Simvastatin is used to lower cholesterol and also exhibits antifungal action. The aim of this study was to evaluate the synergistic action of simvastatin with fluconazole against strains of Candida spp. Susceptibility testing was performed according to protocol M27-A3, by broth microdilution method and the synergistic effect of simvastatin and fluconazole was calculated based on FICI (Fractional Inhibitory Concentration Index. Eleven strains were evaluated, and simvastatin showed a synergistic effect with fluconazole against 10 (91% of the Candida spp. strains tested. Simvastatin may be a valuable drug in the treatment of systemic infections caused by Candida spp.

  13. Fluconazole and testosterone: in vivo and in vitro studies.

    Science.gov (United States)

    Hanger, D P; Jevons, S; Shaw, J T

    1988-05-01

    Fluconazole (UK-49,858), a novel bis-triazole antifungal agent, was given orally to groups of 10 male volunteers at doses of 25 and 50 mg/day for 28 days. Blood samples for testosterone estimation were taken from these and from a placebo group at several time points on days 1, 14, and 28 of the study, and the assay results demonstrated that the compound had no significant effect on circulating testosterone levels. Similarly, in studies with rat Leydig cells in vitro, fluconazole at concentrations up to 10 micrograms/ml was found to be only a weak inhibitor of testosterone production, whereas ketoconazole caused more than 50% inhibition at 0.1 microgram/ml. It is concluded that fluconazole, in contrast to ketoconazole, has little effect on the biosynthesis of testosterone by mammalian cells.

  14. Competitive Fitness of Fluconazole-Resistant Clinical Candida albicans Strains.

    Science.gov (United States)

    Popp, Christina; Hampe, Irene A I; Hertlein, Tobias; Ohlsen, Knut; Rogers, P David; Morschhäuser, Joachim

    2017-07-01

    The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis. Resistance is often caused by gain-of-function mutations in the transcription factors Mrr1 and Tac1, which result in constitutive overexpression of multidrug efflux pumps, and Upc2, which result in constitutive overexpression of ergosterol biosynthesis genes. However, the deregulated gene expression that is caused by hyperactive forms of these transcription factors also reduces the fitness of the cells in the absence of the drug. To investigate whether fluconazole-resistant clinical C. albicans isolates have overcome the fitness costs of drug resistance, we assessed the relative fitness of C. albicans isolates containing resistance mutations in these transcription factors in competition with matched drug-susceptible isolates from the same patients. Most of the fluconazole-resistant isolates were outcompeted by the corresponding drug-susceptible isolates when grown in rich medium without fluconazole. On the other hand, some resistant isolates with gain-of-function mutations in MRR1 did not exhibit reduced fitness under these conditions. In a mouse model of disseminated candidiasis, three out of four tested fluconazole-resistant clinical isolates did not exhibit a significant fitness defect. However, all four fluconazole-resistant isolates were outcompeted by the matched susceptible isolates in a mouse model of gastrointestinal colonization, demonstrating that the effects of drug resistance on in vivo fitness depend on the host niche. Collectively, our results indicate that the fitness costs of drug resistance in C. albicans are not easily remediated, especially when proper control of gene expression is required for successful adaptation to life within a mammalian host. Copyright © 2017 American Society for Microbiology.

  15. Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide

    DEFF Research Database (Denmark)

    Skov, M; Main, K M; Sillesen, Ida Blok

    2002-01-01

    . Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition...

  16. Potent synergistic in vitro interaction between nonantimicrobial membrane-active compounds and itraconazole against clinical isolates of Aspergillus fumigatus resistant to itraconazole.

    NARCIS (Netherlands)

    Afeltra, J.; Vitale, R.G.; Mouton, J.W.; Verweij, P.E.

    2004-01-01

    To develop new approaches for the treatment of invasive infections caused by Aspergillus fumigatus, the in vitro interactions between itraconazole (ITZ) and seven different nonantimicrobial membrane-active compounds--amiodarone (AMD), amiloride, lidocaine, lansoprazole (LAN), nifedipine (NIF),

  17. Incorporation of fluconazole in copolymer PMMA-g-PEG derivatives

    International Nuclear Information System (INIS)

    Silveira, B.M.; Santos, V.M.R. dos; Novack, K.M.; Lopes, S.A.

    2014-01-01

    The graft copolymer PMMA-g-PEG went through chemical transformations in its chain through acetylation, halogenation, methylation and esterification followed by hydrolysis reactions. Subsequently, the copolymer PMMA-g-PEG derivatives passed through the process of emulsification and incorporation of the drug fluconazole. Derivatives copolymers were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) after incorporation in order to evaluate their effectiveness. The efficiency of incorporation was observed and it was also verified that the complexity of polymer chain influence in the incorporated fluconazole content. (author)

  18. Mesomorphous versus traces of crystallinity: The itraconazole example

    Energy Technology Data Exchange (ETDEWEB)

    Atassi, Faraj, E-mail: fatassi@yahoo.com; Behme, Robert J.; Patel, Phenil J.

    2013-12-20

    Highlights: • Characterizing partially disordered pharmaceuticals is very challenging due to the fact that more than one discrete disordered phase can be present. • Dynamic mechanical analysis and dielectric analysis are extremely helpful in characterizing pharmaceutical mesophases (liquid crystals). • Thermotropic pharmaceutical mesophases, often mistaken as amorphous or partially crystalline, can show different phases of liquid crystallinity at different temperature. • Liquid crystalline pharmaceutical materials often show amorphous behavior along with other characteristics specific to mesomorphous materials. • The thermal and mechanical history of pharmaceutical disordered samples has a significant effect on their phase composition. - Abstract: Characterizing disordered pharmaceutical materials can be challenging, especially materials with partially disordered structures that lose one or two directional order (mesophases) and do not fit the traditional characterization categories of amorphous, crystalline or a combination of the two. Itraconazole, an antifungal agent, was chosen as a model compound that, when quench cooled, exhibits atypical disordered structure. Five different analytical tools were used to map out the molecular structure of this material and how it changes with changing temperature. X-ray diffraction showed some remnant crystallinity while dielectric analysis, dynamic mechanical analysis, DSC and hot stage microscopy gave more detailed molecular structure of the disordered material and explained all temperature related structural changes. The characterization of mesomorphous Itraconazole described here will help characterize a wide range of pharmaceuticals that exhibit thermotropic (temperature induced) mesomorphism at the molecular level.

  19. Mesomorphous versus traces of crystallinity: The itraconazole example

    International Nuclear Information System (INIS)

    Atassi, Faraj; Behme, Robert J.; Patel, Phenil J.

    2013-01-01

    Highlights: • Characterizing partially disordered pharmaceuticals is very challenging due to the fact that more than one discrete disordered phase can be present. • Dynamic mechanical analysis and dielectric analysis are extremely helpful in characterizing pharmaceutical mesophases (liquid crystals). • Thermotropic pharmaceutical mesophases, often mistaken as amorphous or partially crystalline, can show different phases of liquid crystallinity at different temperature. • Liquid crystalline pharmaceutical materials often show amorphous behavior along with other characteristics specific to mesomorphous materials. • The thermal and mechanical history of pharmaceutical disordered samples has a significant effect on their phase composition. - Abstract: Characterizing disordered pharmaceutical materials can be challenging, especially materials with partially disordered structures that lose one or two directional order (mesophases) and do not fit the traditional characterization categories of amorphous, crystalline or a combination of the two. Itraconazole, an antifungal agent, was chosen as a model compound that, when quench cooled, exhibits atypical disordered structure. Five different analytical tools were used to map out the molecular structure of this material and how it changes with changing temperature. X-ray diffraction showed some remnant crystallinity while dielectric analysis, dynamic mechanical analysis, DSC and hot stage microscopy gave more detailed molecular structure of the disordered material and explained all temperature related structural changes. The characterization of mesomorphous Itraconazole described here will help characterize a wide range of pharmaceuticals that exhibit thermotropic (temperature induced) mesomorphism at the molecular level

  20. Synergistic inhibition of endothelial cell proliferation, tube formation, and sprouting by cyclosporin A and itraconazole.

    Directory of Open Access Journals (Sweden)

    Benjamin A Nacev

    Full Text Available Pathological angiogenesis contributes to a number of diseases including cancer and macular degeneration. Although angiogenesis inhibitors are available in the clinic, their efficacy against most cancers is modest due in part to the existence of alternative and compensatory signaling pathways. Given that angiogenesis is dependent on multiple growth factors and a broad signaling network in vivo, we sought to explore the potential of multidrug cocktails for angiogenesis inhibition. We have screened 741 clinical drug combinations for the synergistic inhibition of endothelial cell proliferation. We focused specifically on existing clinical drugs since the re-purposing of clinical drugs allows for a more rapid and cost effective transition to clinical studies when compared to new drug entities. Our screen identified cyclosporin A (CsA, an immunosuppressant, and itraconazole, an antifungal drug, as a synergistic pair of inhibitors of endothelial cell proliferation. In combination, the IC(50 dose of each drug is reduced by 3 to 9 fold. We also tested the ability of the combination to inhibit endothelial cell tube formation and sprouting, which are dependent on two essential processes in angiogenesis, endothelial cell migration and differentiation. We found that CsA and itraconazole synergistically inhibit tube network size and sprout formation. Lastly, we tested the combination on human foreskin fibroblast viability as well as Jurkat T cell and HeLa cell proliferation, and found that endothelial cells are selectively targeted. Thus, it is possible to combine existing clinical drugs to synergistically inhibit in vitro models of angiogenesis. This strategy may be useful in pursuing the next generation of antiangiogenesis therapy.

  1. Synergistic inhibition of endothelial cell proliferation, tube formation, and sprouting by cyclosporin A and itraconazole.

    Science.gov (United States)

    Nacev, Benjamin A; Liu, Jun O

    2011-01-01

    Pathological angiogenesis contributes to a number of diseases including cancer and macular degeneration. Although angiogenesis inhibitors are available in the clinic, their efficacy against most cancers is modest due in part to the existence of alternative and compensatory signaling pathways. Given that angiogenesis is dependent on multiple growth factors and a broad signaling network in vivo, we sought to explore the potential of multidrug cocktails for angiogenesis inhibition. We have screened 741 clinical drug combinations for the synergistic inhibition of endothelial cell proliferation. We focused specifically on existing clinical drugs since the re-purposing of clinical drugs allows for a more rapid and cost effective transition to clinical studies when compared to new drug entities. Our screen identified cyclosporin A (CsA), an immunosuppressant, and itraconazole, an antifungal drug, as a synergistic pair of inhibitors of endothelial cell proliferation. In combination, the IC(50) dose of each drug is reduced by 3 to 9 fold. We also tested the ability of the combination to inhibit endothelial cell tube formation and sprouting, which are dependent on two essential processes in angiogenesis, endothelial cell migration and differentiation. We found that CsA and itraconazole synergistically inhibit tube network size and sprout formation. Lastly, we tested the combination on human foreskin fibroblast viability as well as Jurkat T cell and HeLa cell proliferation, and found that endothelial cells are selectively targeted. Thus, it is possible to combine existing clinical drugs to synergistically inhibit in vitro models of angiogenesis. This strategy may be useful in pursuing the next generation of antiangiogenesis therapy.

  2. Myopati hos en patient i behandling med simvastatin og fluconazol

    DEFF Research Database (Denmark)

    Pedersen, Jens Kristian; Lydolph, Magnus Christian; Somnier, Finn

    2016-01-01

    A 69-year-old female was admitted due to progressive loss of muscle strength following addition of fluconazole to long-term simvastatin treatment. Rhabdomyolysis was suspected and both drugs were discontinued. Forced diuresis was initiated together with a short course of prednisolone. After 21...

  3. Fluconazole prophylaxis in preterm infants: a systematic review

    Directory of Open Access Journals (Sweden)

    Juliana Ferreira da Silva Rios

    2017-05-01

    Conclusion: Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens.

  4. Fluconazole treatment hyperpolarizes the plasma membrane of Candida cells

    Czech Academy of Sciences Publication Activity Database

    Elicharová, Hana; Sychrová, Hana

    2013-01-01

    Roč. 51, č. 8 (2013), s. 785-798 ISSN 1369-3786 R&D Projects: GA ČR GAP302/12/1151 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : drug resistance * fluconazol * yeast * hyperpolarization Subject RIV: EE - Microbiology, Virology Impact factor: 2.261, year: 2013

  5. Preparation And Evaluation Of Fluconazole Gels | Abdel-Mottaleb ...

    African Journals Online (AJOL)

    Gels dosage forms are successfully used as drug delivery systems considering their ability to control drug release and to protect medicaments from a hostile environment. Thus, it was desired in this study to formulate fluconazole into a gel that could be used locally in the treatment of different skin fungal infections. Cellulose ...

  6. Subinhibitory concentrations of fluconazole increase the intracellular sodium content in both fluconazole-resistant and -sensitive Candida albicans strains

    Czech Academy of Sciences Publication Activity Database

    Kolecká, A.; Krauke, Yannick; Bujdáková, H.; Sychrová, Hana

    2009-01-01

    Roč. 55, č. 5 (2009), s. 605-610 ISSN 0008-4166 R&D Projects: GA MŠk(CZ) LC531 Grant - others:EC(XE) MRTN-CT-2004-512481 Institutional research plan: CEZ:AV0Z50110509 Keywords : Candida albicans * fluconazol * salt tolerance Subject RIV: EE - Microbiology, Virology Impact factor: 1.262, year: 2009

  7. Thermodynamic scaling of molecular dynamics in supercooled liquid state of pharmaceuticals: Itraconazole and ketoconazole.

    Science.gov (United States)

    Tarnacka, M; Madejczyk, O; Adrjanowicz, K; Pionteck, J; Kaminska, E; Kamiński, K; Paluch, M

    2015-06-14

    Pressure-Volume-Temperature (PVT) measurements and broadband dielectric spectroscopy were carried out to investigate molecular dynamics and to test the validity of thermodynamic scaling of two homologous compounds of pharmaceutical activity: itraconazole and ketoconazole in the wide range of thermodynamic conditions. The pressure coefficients of the glass transition temperature (dT(g)/dp) for itraconazole and ketoconazole were determined to be equal to 183 and 228 K/GPa, respectively. However, for itraconazole, the additional transition to the nematic phase was observed and characterized by the pressure coefficient dT(n)/dp = 258 K/GPa. From PVT and dielectric data, we obtained that the liquid-nematic phase transition is governed by the relaxation time since it occurred at constant τ(α) = 10(-5) s. Furthermore, we plotted the obtained relaxation times as a function of T(-1)v(-γ), which has revealed that the validity of thermodynamic scaling with the γ exponent equals to 3.69 ± 0.04 and 3.64 ± 0.03 for itraconazole and ketoconazole, respectively. Further analysis of the scaling parameter in itraconazole revealed that it unexpectedly decreases with increasing relaxation time, which resulted in dramatic change of the shape of the thermodynamic scaling master curve. While in the case of ketoconazole, it remained the same within entire range of data (within experimental uncertainty). We suppose that in case of itraconazole, this peculiar behavior is related to the liquid crystals' properties of itraconazole molecule.

  8. Comparison of Oral Terbinafine with Itraconazole in the Treatment of Tinea Pedis

    Directory of Open Access Journals (Sweden)

    Memet Bilgili

    2014-03-01

    Full Text Available Aim: The aim of this study was to evaluate the efficacy and safety of oral terbinafine and itraconazole in the treatment of the patients with interdigital tinea pedis. Material and Method: A total 60 patients with clinically and mycologically diagnosed as interdigital tinea pedis were enrolled to the study. Patients were divided into two groups. The first group received oral terbinafine 250 mg/day for two weeks (n:30. The second group received itraconazole 200 mg daily for 7 days (n:30. At the first visit and 15, 30, 60 days after the start of the study, signs and symptoms were assessed clinically and scales were taken for mycological assessments. Results: Six patients who did not return after the first visit were excluded from the study (2 on terbinafine, 4 on itraconazole. The effectiveness of therapy was evaluated at day 15, 30, 60. Symptoms were absent in 57.1% of terbinafine group and 46.1% of the itraconazole group in the first control. The effectiveness of the terbinafine group was 82.1% and 73.1% of the itraconazole group in second control. At day 60, the cure rates were similar (89.3% for terbinafine, 84.6% for itraconazole. No statistical significant differences between the two groups was observed (p>0.05. Discussion: Oral terbinafine and itraconazole have the same effectiveness and tolerability in the treatment of interdigital tinea pedis.

  9. In Vitro Interaction of Terbinafine with Itraconazole against Clinical Isolates of Scedosporium prolificans

    Science.gov (United States)

    Meletiadis, Joseph; Mouton, Johan W.; Rodriguez-Tudela, Juan L.; Meis, Jacques F. G. M.; Verweij, Paul E.

    2000-01-01

    In order to develop new approaches for the chemotherapy of invasive infections caused by Scedosporium prolificans, the in vitro interaction between itraconazole and terbinafine against 20 clinical isolates was studied using a checkerboard microdilution method. Itraconazole and terbinafine alone were inactive against most isolates, but the combination was synergistic against 95 and 85% of isolates after 48 and 72 h of incubation, respectively. Antagonism was not observed. The MICs obtained with the terbinafine-itraconazole combination were within levels that can be achieved in plasma. PMID:10639389

  10. Azasordarins: Susceptibility of Fluconazole-Susceptible and Fluconazole-Resistant Clinical Isolates of Candida spp. to GW 471558

    OpenAIRE

    Cuenca-Estrella, Manuel; Mellado, Emilia; Díaz-Guerra, Teresa M.; Monzón, Araceli; Rodríguez-Tudela, Juan L.

    2001-01-01

    The in vitro activity of the azasordarin GW 471558 was compared with those of amphotericin B, flucytosine, itraconazole, and ketoconazole against 177 clinical isolates of Candida spp. GW 471558 showed potent activity against Candida albicans, Candida glabrata, and Candida tropicalis, even against isolates with decreased susceptibility to azoles. Candida krusei, Candida parapsilosis, Candida lusitaniae, and Candida guilliermondii are resistant to GW 471558 in vitro (MICs, >128 μg/ml).

  11. Successful Long-Term Use of Itraconazole for the Treatment of Aspergillus Diskospondylitis in a Dog

    Directory of Open Access Journals (Sweden)

    Emiko Van Wie

    2013-01-01

    Full Text Available A 5-year-old spayed female German shepherd dog was admitted with a history of generalized stiffness. Neurologic examination revealed mild paraparesis with multifocal spinal pain. Spinal radiographs and magnetic resonance imaging revealed diskospondylitis at L6-7 and multiple sites throughout the thoracolumbar spine. Biopsy of the intervertebral disk at L6-7 revealed a positive culture for Aspergillus species, and the dog was placed on itraconazole indefinitely. Clinical signs were significantly improved after two weeks of itraconazole. The dog was reevaluated 8 years later for unrelated reasons. No spinal pain was detected. Spinal radiographs revealed a fused L6-7 disk space and collapsed and sclerotic disk spaces at multiple sites. Itraconazole was tolerated by the dog with normal yearly liver enzyme values. To our knowledge, this is the first reported case of successful long-term use of itraconazole for the treatment of Aspergillus diskospondylitis in a dog.

  12. The Possible Efficacy of Artichoke in Fluconazole Related Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Hüseyin Kurt

    2014-01-01

    Full Text Available Although fluconazole related hepatotoxicity (FRH is rare, mortal acute hepatic necrosis and jaundice were reported in immunocompromised states such as acquired immunodeficiency syndrome (AIDS and bone marrow transplant (BMT. We present a case of a patient with multiple sclerosis who developed hepatotoxicity with the use of a single 150 mg fluconazole tablet for fungal vaginitis, 10 days after methylprednisolone pulse treatment. Our patient’s alanine aminotransferase (ALT and aspartate aminotransferase (AST levels were decreased, 1200 U/L and 800 U/L, respectively, and bilirubin levels were consistent at 37 mg/dL. Artichoke which has anticholestatic and antioxidant properties was used by our patient. She consumed a 30 mg artichoke leaf extract tea 3 times a day. The bilirubin levels significantly declined at the end of the first week and all liver function tests were normalized within 2 months.

  13. Prevalence & susceptibility to fluconazole of Candida species causing vulvovaginitis.

    Science.gov (United States)

    Mohanty, Srujana; Xess, Immaculata; Hasan, Fahmi; Kapil, Arti; Mittal, Suneeta; Tolosa, Jorge E

    2007-09-01

    Vulvovaginal candidiasis is an important cause of morbidity in women of reproductive age. This study was carried out to determine the species prevalence and susceptibility pattern to fluconazole of yeasts isolated from the vagina of symptomatic women. This prospective study was conducted in a rural primary health care center of north India from May 2003 to April 2004 and included 601 married, sexually active women (18-49 yr) with the self reported symptoms of vaginal discharge and/or genital itching and/or genital burning. Specific aetiology of the genitourinary symptoms including candidal infection were determined. Specimens from the lateral wall of vagina were subjected to direct wet mount microscopy and fungal culture on Sabouraud's dextrose agar. Susceptibility testing to fluconazole was carried out using broth microdilution method. Yeasts were isolated in 111 (18.5%) women and these consisted of Candida glabrata (56, 50.4%), C. albicans (39, 35.1%), C. tropicalis (12, 10.8%), C. krusei (3, 2.7%) and C. parapsilosis (1, 0.9%). Susceptibility testing carried out on 30 representative isolates (15 C. glabrata, 10 C. albicans, 4 C. tropicalis and 1 C. parapsilosis) revealed that 21 isolates (70%) were susceptible (MIC, < or = 8 microg/ml) to fluconazole while 9 (30%) were susceptible-dose dependent (S-DD, MIC 16-32 microg/ml). Our findings suggest a low prevalence of fluconazole resistance in vaginal candida isolates in our population. However, a high prevalence of non-albicans candida species and increased dose-dependent resistance in these isolates necessitates vigilance since this may warrant a change in the optimal therapy of non-albicans candida vaginitis.

  14. CLINICAL EVALUATION OF EFFECTIVENESS OF ITRACONAZOLE IN PREOPERATIVE AND REFRACTORY POSTOPERATIVE PATIENTS OF ALLERGIC FUNGAL SINUSITIS

    Directory of Open Access Journals (Sweden)

    Ch. Venkatasubbaiah

    2016-07-01

    Full Text Available BACKGROUND Allergic Fungal Sinusitis (AFS is a noninvasive type of fungal sinusitis, clinically and pathologically a unique entity of chronic rhinosinusitis. The aetiology, pathogenesis, and treatment of AFS are subject to controversy. In spite of aggressive endoscopic surgery, pre- and postoperative steroids and immunotherapy recurrence rates are high. Many additions are made to its original description and management since its early description in 1980. The aim of the present paper was to evaluate clinically. The response to high-dose itraconazole before endoscopic sinus surgery and in refractory postoperative patients. Related literature was reviewed in the light of the present study. MATERIALS AND METHODS A 2 year prospective study conducted on 68 AFS patients divided into two groups to clinically evaluate the results after using oral itraconazole preoperatively in one group and in refractory postoperative period in another. RESULTS The mean age of patients with typical AFS was 36±3.9 years. Patients with AFS with an average follow up of 21 months were included. Recurrence was 6/34 (17.64% in itraconazole group and revision FESS done in 3/34 (08.82%. Recurrence in patients without itraconazole was 16/34 (47.05% and refractory to conventional treatment, but responded to itraconazole in 14/16 (87.50%. Revision surgery required in 2/16 (12.50% after starting oral itraconazole. No side effects or reactions were observed in a total of 7920 doses administered. CONCLUSION Itraconazole is well tolerated by patients and effective in shrinking the polyposis preoperatively with low recurrence. Postoperative refractory AFS is amenable in (87.50% of patients avoiding repeat FESS. Overall, low recurrence rate and minimizing revision surgery when compared to patients treated without itraconazole was evident in the study.

  15. Effect of Itraconazole on the Pharmacokinetics of Diclofenac in Beagle Dogs

    OpenAIRE

    AL-JENOOBI, Fahad

    2010-01-01

    The objective of this study was to investigate the potential effect of itraconazole on the pharmacokinetics of diclofenac potassium in beagle dogs after oral coadministration. Five male beagle dogs received a single oral 50 mg dose of diclofenac potassium alone in phase I, and along with a single oral 100 mg dose of itraconazole in phase II. Blood samples obtained for 8.0 hours post dose were analysed for diclofenac concentration using a validated high performance liquid chromatography (HPLC)...

  16. An unusual case of lung abscess caused by Acremonium species treated with itraconazole.

    Science.gov (United States)

    Qazi, M S; Bowalekar, S S; Wanjare, V S; Shankar, A

    2015-01-01

    We present a report of a 37-year-old female with lung abscess due to Acremonium species that responded to oral itraconazole. There was a marked clinical as well as radiological improvement in patient. To the best of our knowledge, this is the first case of lung abscess due to Acremonium species which was treated by oral itraconazole. This cost-effective treatment modality proved to be significant in improving symptoms as well as morbidity in this patient.

  17. An unusual case of lung abscess caused by Acremonium species treated with itraconazole

    Directory of Open Access Journals (Sweden)

    M S Qazi

    2015-01-01

    Full Text Available We present a report of a 37-year-old female with lung abscess due to Acremonium species that responded to oral itraconazole. There was a marked clinical as well as radiological improvement in patient. To the best of our knowledge, this is the first case of lung abscess due to Acremonium species which was treated by oral itraconazole. This cost-effective treatment modality proved to be significant in improving symptoms as well as morbidity in this patient.

  18. Formation of itraconazole-succinic acid cocrystals by gas antisolvent cocrystallization.

    Science.gov (United States)

    Ober, Courtney A; Gupta, Ram B

    2012-12-01

    Cocrystals of itraconazole, an antifungal drug with poor bioavailability, and succinic acid, a water-soluble dicarboxylic acid, were formed by gas antisolvent (GAS) cocrystallization using pressurized CO(2) to improve itraconazole dissolution. In this study, itraconazole and succinic acid were simultaneously dissolved in a liquid solvent, tetrahydrofuran, at ambient conditions. The solution was then pressurized with CO(2), which decreased the solvating power of tetrahydrofuran and caused crystallization of itraconazole-succinic acid cocrystals. The cocrystals prepared by GAS cocrystallization were compared to those produced using a traditional liquid antisolvent, n-heptane, for crystallinity, chemical structure, thermal behavior, size and surface morphology, potential clinical relevance, and stability. Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy analyses showed that itraconazole-succinic acid cocrystals with physical and chemical properties similar to cocrystals produced using a traditional liquid antisolvent technique can be prepared by CO(2) antisolvent cocrystallization. The dissolution profile of itraconazole was significantly enhanced through GAS cocrystallization with succinic acid, achieving over 90% dissolution in less than 2 h. The cocrystals appeared stable against thermal stress for up to 4 weeks under accelerated stability conditions, showing only moderate decreases in their degree of crystallinity but no change in their crystalline structure. This study shows the utility of an itraconazole-succinic acid cocrystal for improving itraconazole bioavailability while also demonstrating the potential for CO(2) to replace traditional liquid antisolvents in cocrystal preparation, thus making cocrystal production more environmentally benign and scale-up more feasible.

  19. In Vitro Susceptibilities of Isolates of Sporothrix schenckii to Itraconazole and Terbinafine

    Science.gov (United States)

    Kohler, Lidiane Meire; Monteiro, Paulo César Fialho; Hahn, Rosane Christine; Hamdan, Júnia Soares

    2004-01-01

    Thirty isolates of the yeast form of Sporothrix schenckii were evaluated for in vitro susceptibility to itraconazole and terbinafine by the recommended NCCLS modified technique (M27-A2). The MICs of itraconazole obtained oscillated between 0.062 and 4.0 μg/ml, and those of terbinafine oscillated between 0.007 and 0.50 μg/ml; therefore, terbinafine showed greater in vitro activity. PMID:15365033

  20. The use of (1-3) β-glucan along with itraconazole against canine refractory sporotrichosis.

    Science.gov (United States)

    Guterres, Karina Affeldt; de Matos, Caroline Bohnen; Osório, Luiza Da Gama; Schuch, Isabel Duarte; Cleff, Marlete Brum

    2014-04-01

    Sporotrichosis, caused by the Sporothrix schenckii fungal complex, is a zoonotic mycosis distributed worldwide. Itraconazole is the treatment of choice for domestic animals although some fungal isolates have shown resistance to this drug. The objective of this study was to report, for the first time, the use of (1-3) β-glucan along with itraconazole in the treatment of a canine with sporotrichosis caused by Sporothrix brasiliensis. The animal had ulcerated and crusted lesions, especially on the nasal planum. Clinical samples were collected for a complete blood count, cytological analysis of the lesion, and fungal culture. Based on the results of the laboratory examination, and after the fungal culture, antibiotic therapy and treatment with itraconazole were initiated. Two additional fungal cultures were performed, which were positive. After 7 months of the animal treatment with itraconazole, the S. brasiliensis culture was still positive, so that the itraconazole was associated with (1-3) β-glucan. After four weekly applications of glucan, the complete elimination of the fungus was observed based on the fungal culture negative results. The results show, therefore, that (1-3) β-glucan with itraconazole promoted the case resolution, and it may be considered a promising alternative for the treatment of sporotrichosis in cases of resistance to conventional therapy.

  1. Reversible acute adrenal insufficiency caused by fluconazole in a critically ill patient

    OpenAIRE

    Krishnan, S G Santhana; Cobbs, R K

    2006-01-01

    A 38 year old man with history of obstructive sleep apnea and polycythaemia presented with hypercapnic respiratory failure that required intubation. He developed fever with infiltrates on chest radiography that required empiric antifungal therapy with fluconazole along with broad spectrum antibiotics. He developed acute adrenal insufficiency that recovered after fluconazole was stopped. It is believed that this complication of adrenal suppression attributable to fluconazole is underrecognised...

  2. Reversible acute adrenal insufficiency caused by fluconazole in a critically ill patient

    Science.gov (United States)

    Krishnan, S G Santhana; Cobbs, R K

    2006-01-01

    A 38 year old man with history of obstructive sleep apnea and polycythaemia presented with hypercapnic respiratory failure that required intubation. He developed fever with infiltrates on chest radiography that required empiric antifungal therapy with fluconazole along with broad spectrum antibiotics. He developed acute adrenal insufficiency that recovered after fluconazole was stopped. It is believed that this complication of adrenal suppression attributable to fluconazole is underrecognised and it may be prudent to monitor all critically ill patients who are given fluconazole for this complication. PMID:16954446

  3. Thermodynamic scaling of molecular dynamics in supercooled liquid state of pharmaceuticals: Itraconazole and ketoconazole

    Energy Technology Data Exchange (ETDEWEB)

    Tarnacka, M., E-mail: mtarnacka@us.edu.pl; Madejczyk, O.; Kamiński, K.; Paluch, M. [Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice (Poland); Silesian Center of Education and Interdisciplinary Research, University of Silesia, ul. 75 Pulku Piechoty 1A, 41-500 Chorzow (Poland); Adrjanowicz, K. [NanoBioMedical Centre, ul. Umultowska 85, 61-614 Poznan (Poland); Pionteck, J. [Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, D-01069 Dresden (Germany); Kaminska, E. [Department of Pharmacognosy and Phytochemistry, School of Pharmacy and Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, ul. Jagiellonska 4, 41-200 Sosnowiec (Poland)

    2015-06-14

    Pressure-Volume-Temperature (PVT) measurements and broadband dielectric spectroscopy were carried out to investigate molecular dynamics and to test the validity of thermodynamic scaling of two homologous compounds of pharmaceutical activity: itraconazole and ketoconazole in the wide range of thermodynamic conditions. The pressure coefficients of the glass transition temperature (dT{sub g}/dp) for itraconazole and ketoconazole were determined to be equal to 183 and 228 K/GPa, respectively. However, for itraconazole, the additional transition to the nematic phase was observed and characterized by the pressure coefficient dT{sub n}/dp = 258 K/GPa. From PVT and dielectric data, we obtained that the liquid-nematic phase transition is governed by the relaxation time since it occurred at constant τ {sub α} = 10{sup −5} s. Furthermore, we plotted the obtained relaxation times as a function of T{sup −1}v{sup −γ}, which has revealed that the validity of thermodynamic scaling with the γ exponent equals to 3.69 ± 0.04 and 3.64 ± 0.03 for itraconazole and ketoconazole, respectively. Further analysis of the scaling parameter in itraconazole revealed that it unexpectedly decreases with increasing relaxation time, which resulted in dramatic change of the shape of the thermodynamic scaling master curve. While in the case of ketoconazole, it remained the same within entire range of data (within experimental uncertainty). We suppose that in case of itraconazole, this peculiar behavior is related to the liquid crystals’ properties of itraconazole molecule.

  4. Insufficient fluconazole exposure in pediatric cancer patients and the need for therapeutic drug monitoring in critically ill children

    NARCIS (Netherlands)

    van der Elst, Kim CM; Pereboom, Marieke; van den Heuvel, Edwin R; Kosterink, Jos G W; Scholvinck, Elisabeth H.; Alffenaar, Jan-Willem C

    2014-01-01

    Background. Fluconazole is recommended as first-line treatment in invasive candidiasis in children and infants. Although timely achievement of adequate exposure of fluconazole improves outcome, therapeutic drug monitoring is currently not recommended. Methods. We conducted a retrospective study of

  5. Candida albicans septicemia in a premature infant successfully treated with oral fluconazole

    DEFF Research Database (Denmark)

    Bodé, S; Pedersen-Bjergaard, Lars; Hjelt, K

    1992-01-01

    A premature male infant, birth-weight 1460 g, was treated successfully for a Candida albicans septicemia with orally administered fluconazole for 20 days. Dosage was 5 mg/kg/day. No side effects were seen. Fluconazole may present a major progress in treatment of invasive C. albicans infections...

  6. Can fluconazole concentrations in saliva be used for therapeutic drug monitoring?

    NARCIS (Netherlands)

    Koks, C. H.; Crommentuyn, K. M.; Hoetelmans, R. M.; Mathôt, R. A.; Beijnen, J. H.

    2001-01-01

    The saliva/plasma concentration ratio of fluconazole was investigated in 22 HIV-1-infected individuals with an oropharyngeal Candida infection to determine whether saliva fluconazole concentrations could provide useful information for therapeutic drug monitoring in this population. Steady-state

  7. Cryptococcal cerebrospinal fluid shunt infection treated with fluconazole

    Directory of Open Access Journals (Sweden)

    Daniel Eymard

    1993-01-01

    Full Text Available A 37-year-old woman with a cadaveric renal allotransplantation required intra-cranial shunting devices after a presumptive episode of tuberculous meningitis. Six months later, she developed a culture-proven cryptococcal meningitis. Without having her ventriculo-auricular shunt removed, she was successfully treated with a short course of amphotericin B (335 mg and flucytosine (nine days followed by prolonged therapy with oral fluconazole (400 mg daily for 72 days. Three years post treatment she had no evidence of relapse, and normal renal graft function.

  8. Influence of an acidic beverage (Coca-Cola) on the absorption of itraconazole.

    Science.gov (United States)

    Jaruratanasirikul, S; Kleepkaew, A

    1997-01-01

    To evaluate the effectiveness of Coca-Cola in enhancing the absorption of itraconazole. Eight healthy volunteers were randomized to receive two treatment sequences in a two-way crossover design with a 1-week wash-out period separating each study treatment. Treatment 1, the control, consisted of 100 mg itraconazole with 325 ml water. Treatment II was identical to treatment I, except that itraconazole was administered with 325 ml of Coca-Cola (pH 2.5). Serum itraconazole concentrations, after administration with Coca-Cola (treatment II), were higher than after administration with water (treatment I). The mean AUC was 1.12 vs 2.02 micrograms.h.m1-1, the mean Cmax was 0.14 vs 0.31 micrograms.m1-1 and the mean tmax was 2.56 vs 3.38 h in treatments I and II, respectively. The absorption of itraconazole can be enhanced by Coca-Cola.

  9. Investigation of microemulsion system for transdermal delivery of itraconazole

    Science.gov (United States)

    Chudasama, Arpan; Patel, Vineetkumar; Nivsarkar, Manish; Vasu, Kamala; Shishoo, Chamanlal

    2011-01-01

    A new oil-in-water microemulsion-based (ME) gel containing 1% itraconazole (ITZ) was developed for topical delivery. The solubility of ITZ in oils and surfactants was evaluated to identify potential excipients. The microemulsion existence ranges were defined through the construction of the pseudoternary phase diagrams. The optimized microemulsion was characterized for its morphology and particle size distribution. The optimized microemulsion was incorporated into polymeric gels of Lutrol F127, Xanthan gum, and Carbopol 934 for convenient application and evaluated for pH, drug content, viscosity, and spreadability. In vitro drug permeation of ME gels was determined across excised rat skins. Furthermore, in vitro antimycotic inhibitory activity of the gels was conducted using agar-cup method and Candida albicans as a test organism. The droplet size of the optimized microemulsion was found to be <100 nm. The optimized Lutrol F 127 ME gel showed pH in the range of 5.68±0.02 and spreadability of 5.75±1.396 gcm/s. The viscosity of ME gel was found to be 1805.535±542.4 mPa s. The permeation rate (flux) of ITZ from prepared ME gel was found to be 4.234 μg/cm/h. The release profile exhibited diffusion controlled mechanism of drug release from ME ITZ gel. The developed ME gels were nonirritant and there was no erythema or edema. The antifungal activity of ITZ showed the widest zone of inhibition with Lutrol F127 ME gel. These results indicate that the studied ME gel may be a promising vehicle for topical delivery of ITZ. PMID:22171289

  10. [Two cases of pulmonary aspergilosis, which deteriorated with generic itraconazole].

    Science.gov (United States)

    Saito, Wakana; Shishikura, Yutaka; Nishimaki, Katsushi; Kikuchi, Tadashi; Sasamori, Kan; Kikuchi, Yoshihiro; Miki, Hiroshi

    2014-07-01

    We experienced two cases of pulmonary aspergillosis, which deteriorated during treatment with generic itraconazole (ITCZ) because of low plasma concentration. One case was chronic pulmonary aspergillosis and the other was allergic bronchopulmonary aspergillosis (ABPA). Treatment of both cases was started with a brand-name-ITCZ, and changed to a generic ITCZ. Deterioration of pulmonary aspergillosis occurred after 8 months and 9 months from change to generic ITCZ respectively. In the first case, the ITCZ-plasma concentration was 46.9 ng/mL and of OH-ITCZ 96.5 ng/mL with generic ITCZ at the dose of 300 mg/day, but increased to 1,559.7 ng/mL and to 2,485.0 ng/mL with the brand-name-ITCZ 300 mg/day, respectively. In the second case, the ITCZ-plasma concentration was 27.2 ng/mL and of OH-ITCZ 20.1 ng/mL with 150 mg/day for generic ITCZ, but reached 857.3 ng/mL and to 1,144.2 ng/ml with the brand-name-ITCZ 300 mg/day, respectively. After treatment failure, the first case was changed to voriconazole, then brand-name-ITCZ 300 mg/day, and the second case to the brand-name-ITCZ 300 mg/day, with successful clinical course. Plasma concentrations of ITCZ can differ significantly depending on the patient or type of ITCZ. The ITCZ-plasma concentration should be controlled after changing from a brand-name-ITCZ to a generic ITCZ.

  11. Efficacy of terbinafine and itraconazole on a experimental model of systemic sporotrichosis Eficiência de terbinafina e itraconazol em um modelo experimental de esporotricose sistêmica

    Directory of Open Access Journals (Sweden)

    Ana Raquel Mano Meinerz

    2008-12-01

    Full Text Available Itraconazole is currently considered the drug of choice to treat the diverse clinical presentation of sporotrichosis. On the other hand terbinafine by virtue of its excellent in vitro activity is under comparative evaluation for its therapeutic potential for a wide range of fungal infections. In this study, our aim was to determine the in vivo efficacy of terbinafine and itraconazole on a experimental model of systemic sporotrichosis. 120 rats Wistar received an injection of 2x10³ S. schenckii cells by via the lateral tail vein. After 3 days the animals were treated with terbinafine (250mg/kg and itraconazole (100 mg/kg and their respective diluents. In our model, terbinafine and itraconazole were effective in reducing the number of clinical lesions and positive organ cultures. There was statistical difference between the groups treated with the antifungals in relation to the control groups (pItraconazol é atualmente considerado a droga de escolha para o tratamento das diferentes formas clínicas da esporotricose. Por outro lado a terbinafina devido a sua excelente atividade in vitro está sendo avaliada quanto ao seu potencial terapêutico frente a diversas infecções fúngicas. O objetivo deste estudo foi determinar a eficácia in vivo da terbinafina e itraconazol em um modelo de esporotricose experimental sistêmica. 120 ratos Wistar receberam uma injeção de 2x10³ células de S. schenckii pela veia lateral da cauda. Após 3 dias os animais foram tratados com terbinafina (250mg/kg e itraconazol (100mg/kg e os seus respectivos diluentes. No modelo experimental estudado, a terbinafina e itraconazol se mostraram efetivos reduzindo o número de sintomas clínicos e retroisolamento positivo para o agente. Houve diferenças estatísticas entre os grupos tratados com os antifúngicos em relação aos grupos controle (p<0,05 nas alterações clínicas, achados anatomopatológicos e no retroisolamento do agente, sendo que os animais tratados

  12. Improvement of a Mixture Experiment Model Relating the Component Proportions to the Size of Nanonized Itraconazole Particles in Extemporary Suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Pattarino, Franco; Piepel, Gregory F.; Rinaldi, Maurizio

    2018-05-01

    The Foglio Bonda et al. (2016) (henceforth FB) paper discussed the use of mixture experiment design and modeling methods to study how the proportions of three components in an extemporaneous oral suspension affected the mean diameter of drug particles (the response variable of interest). The three components were itraconazole (ITZ), Tween 20 (TW20), and Methocel® E5 (E5). After publication of the FB paper, the second author of this corrigendum (not an author of the original paper) contacted the corresponding author to point out some errors as well as insufficient explanations in parts of the paper. This corrigendum was prepared to address these issues. The authors of the original paper apologize for any inconveniences to readers.

  13. Cryosurgery in association with itraconazole for the treatment of feline sporotrichosis.

    Science.gov (United States)

    de Souza, Clarissa Pimentel; Lucas, Ronaldo; Ramadinha, Regina H R; Pires, Tifanny B C P

    2016-02-01

    We evaluated the efficacy of cryosurgery in association with itraconazole for the treatment of feline sporotrichosis. We also compared the length of treatment protocol with others reported in the literature. Cats naturally infected with fungi of the Sporothrix schenckii complex were evaluated. Diagnosis was confirmed by cytology and fungal culture. Prior to the cryosurgical procedure, every animal was receiving itraconazole 10 mg/kg/day PO, for different time periods. The same protocol was maintained until 4 weeks after complete healing of the lesions. Eleven of 13 cats were considered clinically cured. The treatment duration ranged from 14-64 weeks (median 32 weeks). The combination of cryosurgery and itraconazole was effective in treating cases of feline sporotrichosis and decreased the treatment length compared with protocols using only medication. © ISFM and AAFP 2015.

  14. Refractory onychomycosis due to Trichophyton rubrum: combination therapy with itraconazole and terbinafine

    Directory of Open Access Journals (Sweden)

    Bonifaz Alexandro

    2011-07-01

    Full Text Available Objectives: Evaluate the efficacy and tolerability of itraconazole plus terbinafine for refractory onychomycosis. This is a prospective clinical trial. Patients with proven Trychophyton rubrum onychomycosis of toenails were enrolled; the treatment consisted of weekly administration: itraconazole 200mg/day and terbinafine 250mg/day, for four months. Results: Thirty-two patients with onychomycosis were studied. Twenty-eight cases had distal subungual onychomycosis and 4 total dystrophic onychomycosis. At the end of the follow-up 17/32 patients had clinical and mycologic cure (53.12%, 5 had clinical improvement only (15.6%, and 10 (31.2% failed. Conclusion: Weekly alternate therapy with itraconazole + terbinafine represents a safe rescue treatment.

  15. Relative bioavailability of itraconazole from an extemporaneously prepared suspension and from the marketed capsules.

    Science.gov (United States)

    Christensen, K J; Gubbins, P O; Gurley, B J; Bowman, J L; Buice, R G

    1998-02-01

    The bioavailability of itraconazole from an extemporaneously prepared suspension was compared with its bioavailability from the commercially available capsules. Ten healthy volunteers were fed breakfast and were then randomly assigned to receive either 400 mg of itraconazole 40-mg/mL oral suspension or four 100-mg itraconazole capsules with 240 mL of water. They were not allowed to rest in a supine position for six hours, eat for four hours, or take any beverages for two hours post-dose. Blood samples were taken immediately after the subjects had eaten and at intervals up to 72 hours post-dose. Serum was separated and stored at -70 degrees C. Serum itraconazole and hydroxyitraconazole concentrations were measured by high-performance liquid chromatography. After 14 days, each subject was given the dosage form that he or she did not previously receive, and testing was repeated. Maximum concentration (Cmax) and time to reach maximum concentration (tmax) were determined, and the area under the serum concentration-versus-time curve from 0 to 72 hours (AUC0-72) was estimated. The suspension:capsule ratios of least-squares means for Cmax, tmax, and AUC0-72 for itraconazole were 0.15 (90% confidence interval [CI], 0.11-0.21), 0.95 (90% CI, 0.75-1.20), and 0.12 (9% CI, 0.06-0.23), respectively. The results for hydroxyitraconazole were similar: 0.19 (0.13-0.28), 0.95 (0.81-1.12), and 0.13 (0.07-0.23), respectively. The bioavailability of itraconazole from the extemporaneously prepared suspension is much lower than that from capsules.

  16. Resistencia de levaduras del género Candida al fluconazol Candida yeast´s resistance to fluconazol

    Directory of Open Access Journals (Sweden)

    Carlos Hernando Gómez Quintero

    2010-12-01

    Full Text Available Las infecciones por levaduras del género Candida sp. son cada vez más prevalentes en pacientes hospitalizados, especialmente en grupos de mayor riesgo como pueden ser pacientes con neoplasia hematológica bajo tratamiento de quimioterapia y en cuidados intensivos. La resistencia de Candida sp. representa un reto terapéutico que deja un menor número de posibilidades para el tratamiento de estas infecciones que se caracterizan, a su vez, por una alta morbimortalidad. Esta revisión describe los mecanismos de resistencia de Candida sp. a fluconazol y los factores de riesgo para la adquisición de éstos.Yeast infections of the genus Candida sp are becoming more prevalent in hospitalized patients, especially in high risk groups such as patients with hematologic malignancy undergoing chemotherapy and in intensive care units. Candida sp's resistance represents a therapeutic challenge that leaves fewer opportunities for the treatment of these infections which are characterized by high morbidity and mortality. This review describes Candida sp's resistance mechanisms to fluconazole and the risk factors for their acquisition.

  17. Singlet versus Triplet Excited State Mediated Photoinduced Dehalogenation Reactions of Itraconazole in Acetonitrile and Aqueous Solutions.

    Science.gov (United States)

    Zhu, Ruixue; Li, Ming-de; Du, Lili; Phillips, David Lee

    2017-04-06

    Photoinduced dehalogenation of the antifungal drug itraconazole (ITR) in acetonitrile (ACN) and ACN/water mixed solutions was investigated using femtosecond and nanosecond time-resolved transient absorption (fs-TA and ns-TA, respectively) and nanosecond time-resolved resonance Raman spectroscopy (ns-TR 3 ) experiments. An excited resonance energy transfer is found to take place from the 4-phenyl-4,5-dihydro-3H-1,2,4-triazol-3-one part of the molecule to the 1,3-dichlorobenzene part of the molecule when ITR is excited by ultraviolet light. This photoexcitation is followed by a fast carbon-halogen bond cleavage that leads to the generation of radical intermediates via either triplet and/or singlet excited states. It is found that the singlet excited state-mediated carbon-halogen cleavage is the predominant dehalogenation process in ACN solvent, whereas a triplet state-mediated carbon-halogen cleavage prefers to occur in the ACN/water mixed solutions. The singlet-to-triplet energy gap is decreased in the ACN/water mixed solvents and this helps facilitate an intersystem crossing process, and thus, the carbon-halogen bond cleavage happens mostly through an excited triplet state in the aqueous solutions examined. The ns-TA and ns-TR 3 results also provide some evidence that radical intermediates are generated through a homolytic carbon-halogen bond cleavage via predominantly the singlet excited state pathway in ACN but via mainly the triplet state pathway in the aqueous solutions. In strong acidic solutions, protonation at the oxygen and/or nitrogen atoms of the 1,2,4-triazole-3-one group appears to hinder the dehalogenation reactions. This may offer the possibility that the phototoxicity of ITR due to the generation of aryl or halogen radicals can be reduced by protonation of certain moieties in suitably designed ITR halogen-containing derivatives.

  18. Fluconazole-containing agar Sabouraud dextrose plates are not useful when screening for susceptibility in Candida albicans.

    Science.gov (United States)

    Bordallo-Cardona, M A; Marcos-Zambrano, L J; Gómez G de la Pedrosa, E; Escribano, P; Bouza, E; Guinea, J; Cantón, R

    2017-04-01

    Fluconazole is an alternative for candidemic patients who are not critically ill. Fluconazole is mainly fungistatic and does not completely inhibit visual Candida albicans growth. We studied the usefulness of fluconazole-containing Sabouraud dextrose agar plates for detecting susceptibility to fluconazole in C. albicans. Adjusted inocula of 19 isolates were transferred directly onto fluconazole-containing Sabouraud dextrose plates (concentrations ranging from 0.125 mg/L to 128 mg/L). The fluconazole MIC in fresh isolates and after growth on the fluconazole-containing plate at 128 mg/L was recorded following the EUCAST EDef 7.2 guidelines. Then isolates were classified according to their degree of trailing production, based on microdilution procedure. All isolates were able to grow on all fluconazole-containing plates, even those isolates susceptible to fluconazole. In fact, we selected isolates with different degrees of trailing based on microdilution procedures. 50% of isolates classified as heavy trailers, 35.71% as moderate trailers, and 14.28% as slight trailers. The use of fluconazole-containing Sabouraud dextrose agar plates was not a reliable method to detect fluconazole susceptibility in C. albicans isolates; growth of the isolates was a trailing effect rather than true resistance.

  19. Fluconazole induces rapid high-frequency MTL homozygosis with microbiological polymorphism in Candida albicans

    Directory of Open Access Journals (Sweden)

    Tsong-Yih Ou

    2017-12-01

    Full Text Available Background: Candida albicans, a common fungal pathogen that can cause opportunistic infections, is regarded as an apparently asexual, diploid fungus. A parasexual cycle was previously found between homozygotes with opposite mating type-like loci (MTLa/α. Fluconazole-resistant strains had a higher proportion of MTL homozygotes, whereas MTL homozygous C. albicans was found in only about 3.2% of clinical strains. MTL heterozygotes had a low frequency (1.4 × 10−4 of white–opaque switching to MTL homozygotes in nature. Methods: Here, a reference C. albicans strain (SC5314 was used in a fluconazole-induced assay to obtain standard opaque MTL homozygous strains and first-generation daughter strains from the fluconazole inhibition zone. Further separation methods were employed to produce second- and third-generation daughter strains. Polymerase chain reaction analysis based on MTL genes was used to define MTL genotypes, and microscopic observations, a flow-cytometric assay, and an antifungal E-test were used to compare microbiological characteristics. Results: MTL homozygotes were found at a high frequency (17 of 35; 48.6% in fluconazole-induced first-generation daughter strains, as were morphological polymorphisms, decreased DNA content, and modified antifungal drug susceptibility. High-frequency MTL homozygosity was identified inside the fluconazole inhibition zone within 24 hours. The DNA content of fluconazole-induced daughter strains was reduced compared with their progenitor SC5314 and standard MTL homozygous strains. Conclusion: Treatment with fluconazole, commonly used to treat invasive candidiasis, inhibited the growth of C. albicans and altered its microbiological characteristics. Our results suggest that fluconazole treatment induces the high frequency of loss of heterozygosity and microbiological polymorphism in C. albicans. Keywords: Candida albicans, fluconazole, loss of heterozygosity, mating type-like gene

  20. Some pharmacokinetic indices of oral fluconazole administration to koalas (Phascolarctos cinereus) infected with cryptococcosis.

    Science.gov (United States)

    Govendir, M; Black, L A; Jobbins, S E; Kimble, B; Malik, R; Krockenberger, M B

    2016-08-01

    Three asymptomatic koalas serologically positive for cryptococcosis and two symptomatic koalas were treated with 10 mg/kg fluconazole orally, twice daily for at least 2 weeks. The median plasma Cmax and AUC0-8 h for asymptomatic animals were 0.9 μg/mL and 4.9 μg/mL·h, respectively; and for symptomatic animals 3.2 μg/mL and 17.3 μg/mL·h, respectively. An additional symptomatic koala was treated with fluconazole (10 mg/kg twice daily) and a subcutaneous amphotericin B infusion twice weekly. After 2 weeks the fluconazole Cmax was 3.7 μg/mL and the AUC0-8 h was 25.8 μg/mL*h. An additional three koalas were treated with fluconazole 15 mg/kg twice daily for at least 2 weeks, with the same subcutaneous amphotericin protocol co-administered to two of these koalas (Cmax : 5.0 μg/mL; mean AUC0-8 h : 18.1 μg/mL*h). For all koalas, the fluconazole plasma Cmax failed to reach the MIC90 (16 μg/mL) to inhibit C. gattii. Fluconazole administered orally at either 10 or 15 mg/kg twice daily in conjunction with amphotericin is unlikely to attain therapeutic plasma concentrations. Suggestions to improve treatment of systemic cryptococcosis include testing pathogen susceptibility to fluconazole, monitoring plasma fluconazole concentrations, and administration of 20-25 mg/kg fluconazole orally, twice daily, with an amphotericin subcutaneous infusion twice weekly. © 2015 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  1. Fluconazole for ketoconazole-resistant oropharyngeal candidiasis in HIV-1 infected patients

    DEFF Research Database (Denmark)

    Thorsen, S; Mathiesen, Lars Reinhardt

    1990-01-01

    The efficacy of fluconazole in doses ranging from 50 to 200 mg/day in controlling oropharyngeal candidiasis was retrospectively evaluated in 16 consecutive HIV-1-infected patients. 13 patients received fluconazole due to failure of treatment with ketoconazole, and among these 11 (84%) initially...... showed complete or partial remission of oropharyngeal candidiasis. 3 (27%) of these subsequently developed failure of treatment within a median observation period of 38 days. No major toxicities were observed. Fluconazole appears promising in the therapy of ketoconazole-resistant candidiasis....

  2. Statin-associated rhabdomyolysis triggered by drug-drug interaction with itraconazole

    DEFF Research Database (Denmark)

    Dybro, Anne Mette; Damkier, Per; Rasmussen, Torsten Bloch

    2016-01-01

    -associated rhabdomyolysis, probably caused by a drug-drug interaction between simvastatin and itraconazole. The patient made full recovery. Three commonly used statins-simvastatin, atorvastatin and lovastatin-are metabolised by the liver enzyme CYP3A4. Several potent inhibitors of this enzyme are known, for example, azole...

  3. Hepatic safety of itraconazole intravenous solution in treatment of invasive fungal infection

    Institute of Scientific and Technical Information of China (English)

    朱利平

    2006-01-01

    Objective To investigate the hepatic safety of itraconazole intravenous solution in the treatment of invasive fungal infection. Methods Forty-nine patients with invasive fungal infection, such as pneumonia, meningitis, endocarditis, and blood stream infection, caused by Aspergillus spp. Cryptococcus neoformans, Candida spp. Penicillium marneffei,and Prototheca wiekerhamii, 50 of which had underlying diseases, including hepatic disea-

  4. Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles (Lipomer) using Box Behnken design.

    Science.gov (United States)

    Gajra, Balaram; Dalwadi, Chintan; Patel, Ravi

    2015-01-21

    The objective of the study was to formulate and to investigate the combined influence of 3 independent variables in the optimization of Polymeric lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal drug Itraconazole and to improve intestinal permeability. The Polymeric lipid hybrid nanoparticle formulation was prepared by the emulsification solvent evaporation method and 3 factor 3 level Box Behnken statistical design was used to optimize and derive a second order polynomial equation and construct contour plots to predict responses. Biodegradable Polycaprolactone, soya lecithin and Poly vinyl alcohol were used to prepare PLHNs. The independent variables selected were lipid to polymer ratio (X1) Concentration of surfactant (X2) Concentration of the drug (X3). The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of Itraconazole PLHNs. Itraconazole PLHNs revealed nano size (210 ± 1.8 nm) with an entrapment efficiency of 83 ± 0.6% and negative zeta potential of -11.7 mV and also enhance the permeability of itraconazole as the permeability coefficient (Papp) and the absorption enhancement ratio was higher. The tunable particle size, surface charge, and favourable encapsulation efficiency with a sustained drug release profile of PLHNs suggesting that it could be promising system envisioned to increase the bioavailability by improving intestinal permeability through lymphatic uptake, M cell of payer's patch or paracellular pathway which was proven by confocal microscopy.

  5. Comparison of combined use of fluconazole and clotrimazole with the sequential dose of fluconazole in the treatment of recurrent Candida vaginitis

    Directory of Open Access Journals (Sweden)

    Tayebeh Gharibi

    2009-09-01

    Full Text Available Background: fluconazole is one of the systemic anti-fungal agents and clotrimazole vaginal cream is a topical agent against Candida Albicans. In this study, comparison between of the two regimes (Fluconazole with and without vaginal clotrimazole in recurrent Candida albicans was assessed .with that of sequential dose of fluconazole for the treatment of Candida vaginitis, this evaluation was done. Methods: A double blind randomized clinical trial was carried out on 80 married women (20-45 years old having chronic vaginal Candidiasis. The patients were divided in to two groups (40 in each. The first groups received two doses of fluconazole at two different timing (Zero and 72 hours along with clotrimazole vaginal cream 1% ( for 7 days . The second group recived only two doses of fluconazole (Zero time and 72 hours later. Then the patients were examined at 2 and 6 weeks after the treatment. Results: The signs and symptoms of disease (itching, erythema, excoriation, edema and fissure in both groups were significantly decreased after two weeks of the treatment (P = 0.00. The final examination of both groups also showed that the treatment was more effective in the first group compared to the second group. The difference was significant statistically (P<0.05. Conclusion: the data shows that adding topical clotrimazole in treatment of patients with recurrent Candida vaginitis Is more effective.

  6. Antifungal activity of fluconazole-loaded natural rubber latex against Candida albicans.

    Science.gov (United States)

    Yonashiro Marcelino, Mônica; Azevedo Borges, Felipe; Martins Costa, Ana Flávia; de Lacorte Singulani, Junya; Ribeiro, Nathan Vinícius; Barcelos Costa-Orlandi, Caroline; Garms, Bruna Cambraia; Soares Mendes-Giannini, Maria José; Herculano, Rondinelli Donizetti; Fusco-Almeida, Ana Marisa

    2018-03-01

    This work aimed to produce a membrane based on fluconazole-loaded natural rubber latex (NRL), and study their interaction, drug release and antifungal susceptibility against Candida albicans. Fluconazole-loaded NRL membrane was obtained by casting method. The Fourier Transform Infrared Spectroscopy showed no modifications either in NRL or fluconazole after the incorporation. Mechanical test presented low Young's modulus and high strain, indicating the membranes have sufficient elasticity for biomedical application. The bio-membrane was able to release the drug and inhibit the growth of C. albicans as demonstrated by disk diffusion and macrodilution assays. The biomembrane was able to release fluconazole and inhibit the growth of C. albicans, representing a promising biomaterial for skin application.

  7. Clinical observation of treatment of fungal corneal ulcer with application of iodine tincture and fluconazole

    Directory of Open Access Journals (Sweden)

    Xue-Fang Chen

    2013-07-01

    Full Text Available AIM: To explore the effect of 30g/L iodine rubbed and debridement of wound together with 2g/L fluconazole in the treatment of fungal corneal ulcers. METHODS: Fifty fungal keratitis cases(50 eyesdiagnosed by corneal smear examination were cleaned locally, iodine blanch. All patients were given 2g/L fluconazole for systemic treatment, treated eye with 2g/L fluconazole eye-drops and loxacin eye-drops, and 30g/L atropine eye ointment dilate the pupils.RESULTS:Fifty cases(50 eyeswere selected, of which, 40 cases were healed, 8 cases were improved and 2 cases were aggravated with operation being given.CONCLUSION:After early and timely diagnosis of fungal keratitis, local debridement, 30g/L iodine rubbed the wound and joint with systemic and local treatment of fluconazole can achieve good effect.

  8. Decreasing candidaemia rate in abdominal surgery patients after introduction of fluconazole prophylaxis*

    DEFF Research Database (Denmark)

    Holzknecht, Barbara; Thorup, Jens Frederik; Arendrup, M C

    2011-01-01

    Clin Microbiol Infect ABSTRACT: Although abdominal surgery is an established risk factor for invasive candidiasis, the precise role of antifungal prophylaxis in these patients is not agreed upon. In 2007, fluconazole was added to the prophylactic antibiotic treatment for patients...

  9. Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

    NARCIS (Netherlands)

    van der Elst, Kim C. M.; Span, Lambert F. R.; van Hateren, Kai; Vermeulen, Karin M.; van der Werf, Tjip S.; Greijdanus, Ben; Kosterink, Jos G. W.; Uges, Donald R. A.; Alffenaar, Jan-Willem C.

    2013-01-01

    Invasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of

  10. Correlation between in vitro and in vivo antifungal activities in experimental fluconazole-resistant oropharyngeal and esophageal candidiasis.

    Science.gov (United States)

    Walsh, T J; Gonzalez, C E; Piscitelli, S; Bacher, J D; Peter, J; Torres, R; Shetti, D; Katsov, V; Kligys, K; Lyman, C A

    2000-06-01

    Oropharyngeal and esophageal candidiasis (OPEC) is a frequent opportunistic mycosis in immunocompromised patients. Azole-resistant OPEC is a refractory form of this infection occurring particularly in human immunodeficiency virus (HIV)-infected patients. The procedures developed by the Antifungal Subcommittee of the National Committee for Clinical Laboratory Standards (NCCLS) are an important advance in standardization of in vitro antifungal susceptibility methodology. In order to further understand the relationship between NCCLS methodology and antifungal therapeutic response, we studied the potential correlation between in vitro susceptibility to fluconazole and in vivo response in a rabbit model of fluconazole-resistant OPEC. MICs of fluconazole were determined by NCCLS methods. Three fluconazole-susceptible (FS) (MIC, /=64 microgram/ml) isolates of Candida albicans from prospectively monitored HIV-infected children with OPEC were studied. FR isolates were recovered from children with severe OPEC refractory to fluconazole, and FS isolates were recovered from those with mucosal candidiasis responsive to fluconazole. Fluconazole at 2 mg/kg of body weight/day was administered to infected animals for 7 days. The concentrations of fluconazole in plasma were maintained above the MICs for FS isolates throughout the dosing interval. Fluconazole concentrations in the esophagus were greater than or equal to those in plasma. Rabbits infected with FS isolates and treated with fluconazole had significant reductions in oral mucosal quantitative cultures (P OPEC due to C. albicans.

  11. Decreasing candidaemia rate in abdominal surgery patients after introduction of fluconazole prophylaxis*

    DEFF Research Database (Denmark)

    Holzknecht, B J; Thorup, J; Arendrup, M C

    2011-01-01

    Clin Microbiol Infect ABSTRACT: Although abdominal surgery is an established risk factor for invasive candidiasis, the precise role of antifungal prophylaxis in these patients is not agreed upon. In 2007, fluconazole was added to the prophylactic antibiotic treatment for patients with gastrointes......Clin Microbiol Infect ABSTRACT: Although abdominal surgery is an established risk factor for invasive candidiasis, the precise role of antifungal prophylaxis in these patients is not agreed upon. In 2007, fluconazole was added to the prophylactic antibiotic treatment for patients...

  12. Fluconazole is a potent inhibitor of antipyrine metabolism in vivo in mice

    Energy Technology Data Exchange (ETDEWEB)

    La Delfa, I.; Zhu, Q.M.; Mo, Z.; Blaschke, T.F.

    1989-01-01

    Fluconazole, a bis-triazole antifungal, is distinguished from imidazole antifungals (e.g. ketoconazole) by its potency and pharmacokinetic characteristics. Imidazole-containing compounds are well documented to inhibit the hepatic cytochrome P-450-dependent enzyme system; whether this effect occurs with a bis-triazole agent is unknown. The (/sup 14/C)antipyrine breath test was employed to investigate the effects of fluconazole on this enzyme system in CD-1 male mice. Control, ketoconazole (100 mg/kg), and fluconazole (1 and 10 mg/kg) were studied in single- and multiple-dose experiments. Fluconazole had potent inhibitory effects on the total (mean = -73% +/- 2%), demethylase (mean = -90% +/- 2%), and nondemethylase (mean = -60% +/- 4%) elimination rate constants (all p less than 0.001). The fraction of the administered radioactivity excreted as /sup 14/CO/sub 2/ was decreased by 50-80% in the fluconazole groups (p less than 0.001). These effects were seen after single- and multiple-dose studies; however, return to baseline occurred more quickly in the multiple-dose group. These effects were significantly more pronounced than those observed with equipotent doses of ketoconazole. These results provide evidence that fluconazole is a potent, partially selective, and reversible inhibitor of the cytochrome P-450-dependent enzyme system in mice. Future studies will be required to assess this property and possible interactions with drugs metabolized by this enzyme system in humans.

  13. Comparison of Fluconazole and Clotrimazole in the Treatment of Acute Candida Albicans Vulvovaginitis

    Directory of Open Access Journals (Sweden)

    Fatemeh Bahadori

    2008-12-01

    Full Text Available Objective: This study compared two antifungal drugs, fluconazole and clotrimazole for the treatment of vulvo vaginal candidiasis. Materials and Methods: This randomized clinical trial was conducted on 120 women with vulvo vaginal candidiasis during a six month period. All patients answered a standard questionnaire containing questions about symptoms of vulvovaginal candidiasis and presence of vaginal discharge and signs of vulvar and vaginal inflammation were documented according to physical examination. Two swabs of vaginal discharge were obtained for each woman, one for direct smear, another for culture. The culture medium was Sabouraud Dextrose Agar (SDA. Patients were randomized into two groups of clotrimazole (vaginal cream for 7 days and 150 mg fluconazole in a single dose. Clinical and paraclinical responses were calculated.Results: Clinical improvement occurred in 96 cases (80%. This value was 86.7% and 73.3%for clotrimazole and fluconazole, respectively (P-value=0.04. Paraclinical response on tenth day of treatment was observed in 87 patients (72.5%. This value was 66.7% and 78.3%for clotrimazole and fluconazole groups, respectively (P-value=0.110. Mean days of treatment was 4.06 ±1.30 days for clotrimazole and 2.70 ±0.78 days for fluconazole (p value =0.031.Conclusion: Most of the clinical and paraclinical responses to the drugs used for the treatment of vulvo vaginal candidiasis are in the favour of fluconazole.

  14. Incorporation of fluconazole in copolymer PMMA-g-PEG derivatives; Incorporacao de fluconazol em ineditos derivados do copolimero PMMA-g-PEG

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, B.M.; Santos, V.M.R. dos; Novack, K.M.; Lopes, S.A., E-mail: vmrebello@yahoo.com.br [Universidade Federal de Ouro Preto (UFOP), MG (Brazil)

    2014-07-01

    The graft copolymer PMMA-g-PEG went through chemical transformations in its chain through acetylation, halogenation, methylation and esterification followed by hydrolysis reactions. Subsequently, the copolymer PMMA-g-PEG derivatives passed through the process of emulsification and incorporation of the drug fluconazole. Derivatives copolymers were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) after incorporation in order to evaluate their effectiveness. The efficiency of incorporation was observed and it was also verified that the complexity of polymer chain influence in the incorporated fluconazole content. (author)

  15. lnteracciones medicamentosas en pacientes bajo tratamiento con itraconazol para diferentes tipos de micosis

    Directory of Open Access Journals (Sweden)

    Adriana L. Fernández

    1999-12-01

    Full Text Available Algunos estudios han reportado un aumento en la frecuencia e importancia de las interacciones del itraconazol en pacientes bajo polifarmacia con fármacos que afectan el sistema enzimático de la citocromo P450 y modifican el metabolismo del azol. Con el propósito de determinar las características epidemiológicas, farmacológicas y clínicas de las interacciones medicamentosas en pacientes bajo tratamiento con itraconazol para diferentes tipos de micosis, se realizó un estudio descriptivo transversal retrospectivo en el que se analizaron 21 historias clínicas de pacientes atendidos en la Corporación para Investigaciones Biológicas durante el período 1994-1997. Entre la población estudiada, seis pacientes presentaron paracoccidioidomicosis; cinco, cromoblastomicosis; cuatro, histoplasmosis; cuatro, criptococosis, y dos, aspergilosis. En promedio, la dosis de itraconazol, la duración y el número de fármacos recibidos concomitantes fueron 223,8 mgldia, 44,3 semanas y 2,7 fármacos, respectivamente. En 10 individuos, se presentaron enfermedades de base y en 15, enfermedades concomitantes. Se documentó interacción medicamentosa (niveles no detectables o no terapéuticos de itraconazol en 18 pacientes, de los cuales 17 presentaban sospecha clínica y 14 sospecha paraclínica de interacción. El medicamento más frecuentemente involucrado con interacción fue la rifampicina, seguido de los inhibidores H, antiácidos y fenitoina. Similar a lo encontrado en otros estudios, la administración concomitante de estos fármacos con el itraconazol, reduce los niveles séricos de este último y altera la respuesta clínica al tratamiento. Este estudio es una aproximación inicial, aún no realizada en nuestra población, que permitirá establecer protocolos para el manejo y prevención de interacciones medicamentosas en pacientes en tratamiento con itraconazol y otros fármacos.

  16. Suscetibilidade in vitro de isolados de Sporothrix schenckii frente à terbinafina e itraconazol In vitro susceptibility of isolates of Sporothrix schenckii to terbinafine and itraconazole

    Directory of Open Access Journals (Sweden)

    Ana Raquel Mano Meinerz

    2007-02-01

    Full Text Available O estudo objetiva determinar a atividade in vitro da terbinafina e itraconazol através da técnica de microdiluição em caldo (NCCLSM27-A2 adaptado para um fungo dimórfico frente a 12 isolados de Sporothrix schenckii, sendo seis de esporotricose felina, três de esporotricose humana, um isolado de cão e dois isolados humanos provenientes do Instituto Oswaldo Cruz (IOC. O inóculo e as concentrações antifúngicas foram distribuídas em microplacas, as quais foram incubadas a 35°C por cinco dias, quando foi realizada a leitura da concentração inibitória mínima. A concentração inibitória mínima para a terbinafina variou de 0,055µg/ml a 0,109µg/ml e para o itraconazol de 0,219µg/ml a 1,75µg/ml, sendo que para ambos os fármacos as CIMs entre os isolados do IOC foi de 0,875µg/ml. O estudo demonstrou uma alta suscetibilidade do Sporothrix schenckii frente à terbinafina, necessitando mais estudos que correlacionem os testes in vitro frente ao fármaco com a resposta clínica em pacientes com esporotricose.The study objective was to determine the in vitro activity of terbinafine and itraconazole through the microdilution technique in broth (NCCLSM27-A2, adapted for dimorphic fungus, in relation to 12 isolates of Sporothrix schenckii. Six were from feline sporotrichosis, three from human sporotrichosis, one from a dog and two from human isolates originating from Instituto Oswaldo Cruz. The inoculum and antifungal concentrates were distributed on microplates that were incubated at 35°C for five days. Minimum inhibitory concentration readings were made at the end of this period. The MIC for terbinafine ranged from 0.055µg/ml to 0.109µg/ml, and the MIC for itraconazole ranged from 0.219µg/ml to 1.75µg/ml. For both drugs, the MIC from the isolates from IOC was 0.875µg/ml. The present study demonstrates the high susceptibility of Sporothrix schenckii to terbinafine. Further studies to correlate the in vitro susceptibility tests with

  17. Identification of Candida species in patients with oral lesion undergoing chemotherapy along with minimum inhibitory concentration to fluconazole

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    Mehrnoush Maheronnaghsh

    2016-01-01

    Conclusion: Data were shown that C. albicans is the most commonly identified species in oral candidiasis and majority of fluconazole resistant C. albicans were found in patients with gastrointestinal cancer and lymphoma. Therefore, we recommend an alternative drug instead of fluconazole as a first line of treatment for these type of cancers and administration of fluconazole in patients undergoing chemotherapy should be prescribed in accordance with the type of cancer.

  18. Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

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    Letícia Aparecida Schiave

    2018-01-01

    Full Text Available Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400–800 mg.

  19. Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections.

    Science.gov (United States)

    Schiave, Letícia Aparecida; Nascimento, Erika; Vilar, Fernando Crivelenti; de Haes, Tissiana Marques; Takayanagui, Osvaldo Massaiti; Gaitani, Cristiane Masetto de; Martinez, Roberto

    Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800mg. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  20. Effects of fluconazole treatment of mice infected with fluconazole-susceptible and -resistant Candida tropicalis on fungal cell surface hydrophobicity, adhesion and biofilm formation

    Directory of Open Access Journals (Sweden)

    R L Kanoshiki

    2015-01-01

    Full Text Available Background : The incidence of Candida tropicalis less susceptible to fluconazole (FLC has been reported in many parts of the world. Objectives : The aim of this study was to examine the changes of putative virulence attributes of Candida tropicalis accompanying the development of resistance to FLC in vitro and in vivo. Materials and Methods : A FLC-resistant strain (FLC-R was obtained after sequential exposure of a clinical isolate FLC-sensitive (FLC-S to increasing concentrations of the antifungal. The course of infection by both strains was analyzed in BALB/c mice. Analyses of gene expression were performed by real-time polymerase chain reaction PCR. The cell surface hydrophobicity, adhesion and biofilm formation were also determined. Results : Development of resistance to FLC could be observed after 15 days of subculture in azole-containing medium. Overexpression of MDR1 and ERG11 genes were observed in FLC-R, and this strain exhibited enhanced virulence in mice, as assessed by the mortality rate. All mice challenged with the FLC-R died and FLC-treatment caused earlier death in mice infected with this strain. All animals challenged with FLC-S survived the experiment, regardless of FLC-treatment. Overall, FLC-R derivatives strains were significantly more hydrophobic than FLC-S strains and showed greater adherence and higher capacity to form biofilm on polystyrene surface. Conclusions : The expression of virulence factors was higher in FLC-R-C. tropicalis and it was enhanced after FLC-exposure. These data alert us to the importance of identifying microorganisms that show resistance to the antifungals to establish an appropriate management of candidiasis therapy.

  1. Paracoccidioidomicose evidenciando comprometimento medular tratada com sucesso por fluconazol

    Directory of Open Access Journals (Sweden)

    Leandro Pajuaba de Moura

    1994-03-01

    Full Text Available O envolvimento do sistema nervoso central na paracoccidioidomicose tem sido raramente descrito na literatura e sua frequência varia de 9,99% a 27,27%, manifestando-se basicamente sob duas formas clínicas: meníngea e pseudotumoral (abscessos, granulomas, nódulos ou cistos. O Paracoccidioides brasiliensis incide principalmente nos hemisférios cerebrais, podendo acometer ainda cerebelo, ponte, bulbo, meninges cerebrais e raquidianas, sendo excepcional o comprometimento do parênquima medular. Os autores apresentam o caso de um paciente com paracoccidioidomicose com evidências clínicas de comprometimento medular, comprovada por exames complementares indiretos pouco invasivos. Destacam a resposta terapêutica inédita a novo agente antifúngico bistriazólico, o fluconazol, pela primeira vez utilizado nesta forma de apresentação clínica da doença. Salientam a rariedade do comprometimento medular, o diagnóstico através de propedêutica não cirúrgica e a excelente resposta a este novo tratamento.

  2. Vaginal nystatin versus oral fluconazole for the treatment for recurrent vulvovaginal candidiasis.

    Science.gov (United States)

    Fan, Shangrong; Liu, Xiaoping; Wu, Cong; Xu, Lixuan; Li, Jianling

    2015-02-01

    Recurrent vulvovaginal candidiasis (RVVC) is a common condition that can physically and psychologically impact patients. We compared the efficacy and safety of vaginal nystatin suppositories for 14 days each month versus standard oral fluconazole regimens for the treatment for RVVC. Patients (n = 293) were enrolled in the study from April 2010 to September 2013. After the initial therapy, the mycological cure rates were 78.3% (119/152) and 73.8% (104/141) in the nystatin group and fluconazole group, respectively (95% CI, 0.749-2.197, p > 0.05). The mycological cure rates at the end of maintenance therapy were 80.7% (96/119) and 72.7% (72/99) in the two groups, respectively (95% CI, 0.954-3.293, p > 0.05).The mycological cure rates at the end without treatment for 6 months were 81.25% (78/96) and 82.19% (60/73) in the two groups, respectively (95% CI, 0.427-2.066, p > 0.05). The mycological cure rates of RVVC caused by C. albicans were 84.0% (89/106) and 81.8% (99/121) in the two groups, respectively. The mycological cure rates of RVVC caused by C. glabrata were 64.3% (27/42) and 12.5% (2/16) in the two groups, respectively. The initial and 6-month maintenance therapy were successful in five of the nine patients in the nystatin group with RVVC caused by fluconazole-resistant Candida, whereas in the fluconazole group, initial therapy failed in all patients with RVVC caused by fluconazole-resistant Candida (n = 7). We conclude that both fluconazole and nystatin therapies are effective in treating RVVC. Nystatin may also be effective for the treatment for RVVC caused by C. glabrata or fluconazole-resistant Candida.

  3. [Multiple digestive involvement in visceral leishmaniasis in a patient with HIV infection: favourable course with itraconazole].

    Science.gov (United States)

    Béchade, D; Seurat, L; Discamps, G; Tanière, P H; Du Bourguet, F

    1996-01-01

    We report a case of visceral leishmaniasis due to Leishmania infantum in a 35 year-old patient with acquired immunodeficiency syndrome who complained of chronic diarrhea. Biopsy specimens of gastric and duodenal mucosa and bone marrow aspirate led to the diagnosis. Enterocytozoon bieneusi, fortuitously found in the duodenal mucosa, did not seem to be the causative agent of diarrhea in this case, but its association with visceral leishmaniasis is rare. A treatment with itraconazole brought about a sustained clinical remission.

  4. Effect of Itraconazole and Rifampin on the Pharmacokinetics of Olaparib in Patients With Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Dirix, Luc; Swaisland, Helen; Verheul, Henk M W

    2016-01-01

    ) and inducer (rifampin) to alter the pharmacokinetic (PK) profile of olaparib following single oral tablet doses. METHODS: Two Phase I, open-label, non-randomized trials were conducted in patients with advanced solid tumors. In Study 7, patients received olaparib alone and co-administered with itraconazole...... analysis following treatment with olaparib alone and olaparib plus itraconazole, respectively; in Study 8 (N = 22; 4 male, 18 female), all patients were evaluable. Co-administration of olaparib with itraconazole resulted in a statistically significant increase in the relative bioavailability of olaparib......: Cmax treatment ratio, 1.42 (90% CI, 1.33-1.52); mean AUC treatment ratio, 2.70 (90% CI, 2.44-2.97). Mean CL/F and Vz/F were reduced (8.16 vs 3.05 L/h and 192 vs 75.1 L), although mean t½ was unchanged (15.0 vs 15.6 hours). Co-administration of olaparib with rifampin resulted in a statistically...

  5. Antifungal activity of essential oils from Iranian plants against fluconazole-resistant and fluconazole-susceptible Candida albicans

    Directory of Open Access Journals (Sweden)

    Aghil Sharifzadeh

    2016-03-01

    Full Text Available Objectives: The purpose of this study was to assay the antifungal activity of selected essential oils obtained from plants against both fluconazole (FLU-resistant and FLU-susceptible C. albicans strains isolated from HIV positive patients with oropharyngeal candidiasis (OPC. Materials and Methods: The essential oils were obtained by hydrodistillation method from Myrtus communis (My. communis, Zingiber officinale roscoe (Z. officinale roscoe, Matricaria chamomilla (Ma. chamomilla, Trachyspermum ammi (T. ammi and Origanum vulgare (O. vulgare. The susceptibility test was based on the M27-A2 methodology. The chemical compositions of the essential oils were obtained by gas chromatography- mass spectroscopy (GC-MS. Results: In GC-MS analysis, thymol (63.40%, linalool (42%, α-pinene (27.87%, α-pinene (22.10%, and zingiberene (31.79% were found to be the major components of T. ammi, O. vulgare, My. communis, Ma. chamomilla and Z. officinale roscoe, respectively. The results showed that essential oils have different levels of antifungal activity. O. vulgare and T. ammi essential oils were found to be the most efficient (P

  6. Cdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates.

    LENUS (Irish Health Repository)

    2011-05-01

    The development of resistance to azole antifungals used in the treatment of fungal infections can be a serious medical problem. Here, we investigate the molecular mechanisms associated with reduced susceptibility to fluconazole in clinical isolates of Candida dubliniensis , showing evidence of the trailing growth phenomenon. The changes in membrane sterol composition were studied in the presence of subinhibitory fluconazole concentrations. Despite lanosterol and eburicol accumulating as the most prevalent sterols after fluconazole treatment, these ergosterol precursors still support growth of Candida isolates. The overexpression of ABC transporters was demonstrated by immunoblotting employing specific antibodies against Cdr1p and Cdr2p. The presence of a full-length 170 kDa protein Cdr1p was detected in two isolates, while a truncated form of Cdr1p with the molecular mass of 85 kDa was observed in isolate 966\\/3(2). Notably, Cdr2p was detected in this isolate, and the expression of this transporter was modulated by subinhibitory concentrations of fluconazole. These results suggest that C. dubliniensis can display the trailing growth phenomenon, and such isolates express similar molecular mechanisms like that of fluconazole-resistant isolates and can therefore be associated with recurrent infections.

  7. Comparison of oral itraconazole and intramuscular meglumine antimoniate in the treatment of cutaneous leishmaniasis

    International Nuclear Information System (INIS)

    Saleem, K.; Rahman, A.

    2007-01-01

    To compare the efficacy and tolerability of oral itraconazole against intramuscular meglumine antimoniate in the treatment of Cutaneous Leishmaniasis (CL). Two hundred eligible and consenting patients of Cutaneous Leishmaniasis (CL) were divided in two groups with 100 patients in each. The number and location of the lesions were documented and clinical types of cutaneous leishmaniasis were noted. The diagnosis was confirmed by skin slit smear and histopathology of the lesional skin. Culture on Nicolle Novy MacNeal (NNN) medium and Leishmanin test was done in all patients. All the patients in both groups were subjected to complete blood picture, urine examination, serum urea and creatinine levels and ECG examination. One group was given itraconazole 100 mg twice daily orally for a duration of 6-8 weeks. The other group was given meglumine antimoniate 10 cc in the form of deep intramuscular injections for 15-30 days. The efficacy of the treatment was judged by clinical and parasitological response. Side effects of the agents were also noted during treatment. Out of 200 patients studied, 185 were males and 15 were females. The mean age of presentation was 30 + 6.6 years. Single lesion was seen in 132 (66%) subjects whereas 68 (34%) subjects had multiple lesions. Slit skin smears were positive in 50 (25%) of the patients. Skin biopsy yielded the presence of LT bodies in 150 (75%) subjects. The culture was positive in 102 (51%) cases. Leishmanin test was positive in 94% subjects. Seventy-five (75%) patients on itraconazole therapy showed complete clinical and parasitological cure in 4-8 weeks duration. A rise in ALT was seen in 12% subjects. Five (5%) subjects did not show any improvement till the end of therapy. Sixty-five (65%) subjects on meglumine antimoniate showed complete healing in 15-30 days. In 35 (35%) of the patients, the treatment had to be stopped due to intolerable side-effects. Four cases of lupoid leishmaniasis and 4 cases of sporotrichoid leishmaniasis

  8. Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis

    Science.gov (United States)

    Evans, E Glyn V; Sigurgeirsson, Bárdur

    1999-01-01

    Objective To compare the efficacy and safety of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis. Design Prospective, randomised, double blind, double dummy, multicentre, parallel group study lasting 72 weeks. Setting 35 centres in six European countries. Subjects 496 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte onychomycosis of the toenail. Interventions Study patients were randomly divided into four parallel groups to receive either terbinafine 250 mg a day for 12 or 16 weeks (groups T12 and T16) or itraconazole 400 mg a day for 1 week in every 4 weeks for 12 or 16 weeks (groups I3 and I4). Main outcome measures Assessment of primary efficacy at week 72 was mycological cure, defined as negative results on microscopy and culture of samples from the target toenail. Results At week 72 the mycological cure rates were 75.7% (81/107) in the T12 group and 80.8% (80/99) in the T16 group compared with 38.3% (41/107) in the I3 group and 49.1 % (53/108) in the I4 group. All comparisons (T12 v I3, T12 v I4, T16 v I3, T16 v I4) showed significantly higher cure rates in the terbinafine groups (all Pterbinafine at week 72. There were no differences in the number or type of adverse events recorded in the terbinafine or itraconazole groups. Conclusion Continuous terbinafine is significantly more effective than intermittent itraconazole in the treatment of patients with toenail onychomycosis. Key messagesGiven a correct diagnosis, fungal nail disease (onychomycosis) is curableTerbinafine is an allylamine antifungal with a primarily fungicidal mode of actionContinuous terbinafine treatment over 12 or 16 weeks achieves higher rates of clinical and mycological cure than intermittent itraconazole given over the same periodsTerbinafine is safe and well tolerated over 12 or 16 weeks of continuous treatmentContinuous terbinafine should be the current treatment of choice for onychomycosis PMID

  9. In vitro activity of fluconazole and amphotericin B against Candida inconspicua clinical isolates as determined by the time-kill method

    DEFF Research Database (Denmark)

    Szabó, Zsuzsanna; Sóczó, Georgina; Miszti, Cecilia

    2008-01-01

    Candida inconspicua is an emerging pathogen in immunocompromised patients possessing inherently decreased susceptibility to fluconazole. We determined the MICs and killing activity of fluconazole and amphotericin B against C. inconspicua clinical isolates as well as reference strain C. inconspicu...

  10. Risk of Psoriasis Following Terbinafine or Itraconazole Treatment for Onychomycosis: A Population-Based Case-Control Comparative Study.

    Science.gov (United States)

    Chiu, Hsien-Yi; Chang, Wei-Lun; Tsai, Tsen-Fang; Tsai, Yi-Wen; Shiu, Ming-Neng

    2018-03-01

    Several case studies have reported an association between antifungal drug use and psoriasis risk. The objective of this study was to investigate the association between terbinafine/itraconazole exposure and psoriasis incidence. Among patients with onychomycosis in the Taiwan National Health Insurance Research Database, 3831 incident psoriasis cases were identified during 2004-2010 and compared with 3831 age- and sex-matched controls with the same look-back period. Multivariate conditional logistic regression was used for the analysis. The psoriasis cases were significantly more likely than matched controls to have used terbinafine or itraconazole (59.85 vs. 42.70%, respectively; p terbinafine/itraconazole use was associated with an increased psoriasis risk (adjusted odds ratio 1.33, 95% confidence interval 1.15-1.54). The association was stronger for more recent drug exposure (adjusted odds ratio 2.96, 95% confidence interval 2.25-3.90 for ≤ 90 days before the sampling date; adjusted odds ratio 1.04, 95% confidence interval 0.89-1.22 for > 360 days). In a comparison of patients receiving terbinafine or itraconazole only, psoriasis risk was higher for itraconazole (adjusted odds ratio 1.21, 95% confidence interval 1.05-1.40). This large population-based case-control analysis showed that exposure to terbinafine or itraconazole is associated with an increased risk of incident psoriasis. The finding of an increased psoriasis risk for antifungal drug users, particularly for itraconazole, deserves attention in clinical practice although further prospective studies are necessary to confirm our findings and clarify the biological mechanisms that underlie these associations.

  11. Comparative study of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis.

    Science.gov (United States)

    Francesconi, Glaucia; Francesconi do Valle, Antonio Carlos; Passos, Sonia Lambert; de Lima Barros, Mônica Bastos; de Almeida Paes, Rodrigo; Curi, André Luiz Land; Liporage, José; Porto, Cássio Ferreira; Galhardo, Maria Clara Gutierrez

    2011-05-01

    Itraconazole is currently used for the treatment of cutaneous sporotrichosis. Terbinafine at a daily dose of 250 mg has been successfully applied to the treatment of cutaneous sporotrichosis. To compare the efficacy of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis. A bidirectional cohort study was conducted on 55 patients receiving 250 mg/day terbinafine and 249 patients receiving 100 mg/day itraconazole. The latter patients were matched for age and clinical form to the terbinafine group at a ratio of 5:1. Sporothrix schenckii was isolated by culture from all patients (age range: 18-70 years), who were submitted to the standard care protocol consisting of clinical and laboratory evaluation and periodic visits. Cure was observed in 51 (92.7%) patients of the terbinafine group and 229 (92%) of the itraconazole group within a similar mean period of time (11.5 and 11.8 weeks, respectively). An increase in the terbinafine dose to 500 mg was necessary in two patients due to the lack of a response, and one patient presented recurrence. In the itraconazole group, two patients required a dose increase and three presented recurrence. Adverse events were equally frequent among patients receiving terbinafine (n = 4, 7.3%) and itraconazole (n = 19, 7.6%) and were generally mild without the need for drug discontinuation, except for two patients of the itraconazole group. Terbinafine administered at a daily dose of 250 mg is an effective and well-tolerated option for the treatment of cutaneous sporotrichosis.

  12. Fluconazole for empiric antifungal therapy in cancer patients with fever and neutropenia

    Directory of Open Access Journals (Sweden)

    Peterson Josh F

    2006-12-01

    Full Text Available Abstract Background Several clinical trials have demonstrated the efficacy of fluconazole as empiric antifungal therapy in cancer patients with fever and neutropenia. Our objective was to assess the frequency and resource utilization associated with treatment failure in cancer patients given empiric fluconazole antifungal therapy in routine inpatient care. Methods We performed a retrospective cohort study of cancer patients treated with oral or intravenous fluconazole between 7/97 and 6/01 in a tertiary care hospital. The final study cohort included cancer patients with neutropenia (an absolute neutrophil count below 500 cells/mm3 and fever (a temperature above 38°C or 100.4°F, who were receiving at least 96 hours of parenteral antibacterial therapy prior to initiating fluconazole. Patients' responses to empiric therapy were assessed by reviewing patient charts. Results Among 103 cancer admissions with fever and neutropenia, treatment failure after initiating empiric fluconazole antifungal therapy occurred in 41% (95% confidence interval (CI 31% – 50% of admissions. Patients with a diagnosis of hematological malignancy had increased risk of treatment failure (OR = 4.6, 95% CI 1.5 – 14.8. When treatment failure occurred the mean adjusted increases in length of stay and total costs were 7.4 days (95% CI 3.3 – 11.5 and $18,925 (95% CI 3,289 – 34,563, respectively. Conclusion Treatment failure occurred in more than one-third of neutropenic cancer patients on fluconazole as empiric antifungal treatment for fever in routine clinical treatment. The increase in costs when treatment failure occurs is substantial.

  13. Amphotericin B versus fluconazole for controlling fungal infections in neutropenic cancer patients

    DEFF Research Database (Denmark)

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2014-01-01

    BACKGROUND: Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever. OBJECTIVES: To compare the effect...... of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia. SEARCH METHODS: We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles. SELECTION CRITERIA: Randomised clinical trials comparing fluconazole with amphotericin B...

  14. Analytical and semipreparative chiral separation of cis-itraconazole on cellulose stationary phases by high-performance liquid chromatography.

    Science.gov (United States)

    Kurka, Ondřej; Kučera, Lukáš; Bednář, Petr

    2016-07-01

    cis-Itraconazole is a chiral antifungal drug administered as a racemate. The knowledge of properties of individual cis-itraconazole stereoisomers is vital information for medicine and biosciences as different stereoisomers of cis-itraconazole may possess different affinity to certain biological pathways in the human body. For this purpose, either chiral synthesis of enantiomers or chiral separation of racemate can be used. This paper presents a two-step high-performance liquid chromatography approach for the semipreparative isolation of four stereoisomers (two enantiomeric pairs) of itraconazole using polysaccharide stationary phases and volatile organic mobile phases without additives in isocratic mode. The approach used involves the separation of the racemate into three fractions (i.e. two pure stereoisomers and one mixed fraction containing the remaining two stereoisomers) in the first run and consequent separation of the collected mixed fraction in the second one. For this purpose, combination of cellulose tris-(4-methylbenzoate) and cellulose tris-(3,5-dimehylphenylcarbamate) columns with complementary selectivity for cis-itraconazole provided full separation of all four stereoisomers (with purity of each isomer > 97%). The stereoisomers were collected, their optical rotation determined and their identity confirmed based on the results of a previously published study. Pure separated stereoisomers are subjected to further biological studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Tratamiento con caspofungina de endocarditis por Candida tropicalis resistente a fluconazol Treatment with caspofungin of Candida tropicalis endocarditis resistant to fluconazol

    Directory of Open Access Journals (Sweden)

    Marcelo del Castillo

    2004-04-01

    Full Text Available Las endocarditis causadas por hongos, (Candida en particular, requieren tratamiento médico-quirúrgico, siendo la anfotericina B la droga de elección. Caspofungina es una equinocandina con gran actividad sobre Candida y Aspergillus. Se presenta un paciente con una endocarditis por Candida tropicalis resistente a fluconazol tratado con caspofungina bajo un esquema de salvataje, luego de haber presentado efectos adversos por anfotericina B. El paciente tuvo respuesta microbiológica.Fungal endocarditis, in particular due to Candida species, requires medical and surgical treatment and amphotericin B is the drug of choice. Caspofungin is an echinocandin very effective against Candida and Aspergillus. We present a patient with Candida tropicalis endocarditis, fluconazol resistant, treated with caspofungin, on a compassional basis as a result of adverse effects with amphotericin B. The patient had a microbiological response.

  16. Effects of terbinafine and itraconazole on the pharmacokinetics of orally administered tramadol.

    Science.gov (United States)

    Saarikoski, Tuukka; Saari, Teijo I; Hagelberg, Nora M; Backman, Janne T; Neuvonen, Pertti J; Scheinin, Mika; Olkkola, Klaus T; Laine, Kari

    2015-03-01

    Tramadol is widely used for acute, chronic, and neuropathic pain. Its primary active metabolite is O-desmethyltramadol (M1), which is mainly accountable for the μ-opioid receptor-related analgesic effect. Tramadol is metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other metabolites by CYP3A4 and CYP2B6. We investigated the possible interaction of tramadol with the antifungal agents terbinafine (CYP2D6 inhibitor) and itraconazole (CYP3A4 inhibitor). We used a randomized placebo-controlled crossover study design with 12 healthy subjects, of which 8 were extensive and 4 were ultrarapid CYP2D6 metabolizers. On the pretreatment day 4 with terbinafine (250 mg once daily), itraconazole (200 mg once daily) or placebo, subjects were given tramadol 50 mg orally. Plasma concentrations of tramadol and M1 were determined over 48 h and some pharmacodynamic effects over 12 h. Pharmacokinetic variables were calculated using standard non-compartmental methods. Terbinafine increased the area under plasma concentration-time curve (AUC0-∞) of tramadol by 115 % and decreased the AUC0-∞ of M1 by 64 % (P Terbinafine increased the peak concentration (C max) of tramadol by 53 % (P terbinafine pretreatment the elimination half-life of tramadol and M1 were increased by 48 and 50 %, respectively (P Terbinafine reduced subjective drug effect of tramadol (P Terbinafine may reduce the opioid effect of tramadol and increase the risk of its monoaminergic adverse effects. Itraconazole has no meaningful interaction with tramadol in subjects who have functional CYP2D6 enzyme.

  17. Oral terbinafine and itraconazole treatments against dermatophytes appear not to favor the establishment of Fusarium spp. in nail.

    Science.gov (United States)

    Verrier, Julie; Bontems, Olympia; Baudraz-Rosselet, Florence; Monod, Michel

    2014-01-01

    Fusarium onychomycoses are weakly responsive or unresponsive to standard onychomycosis treatments with oral terbinafine and itraconazole. To examine whether the use of terbinafine and itraconazole, which are highly effective in fighting Trichophyton onychomycoses, could be a cause of the high incidence of Fusarium nail infections. Polymerase chain reaction methods were used to detect both Fusarium spp. and Trichophyton spp. in nails of patients who had either received treatment previously or not. No significant microbiological differences were found between treated and untreated patients. In 24 of 79 cases (30%), Fusarium spp. was detected in samples of patients having had no previous antifungal therapy and when Trichophyton spp. grew in culture. Oral terbinafine and itraconazole treatments do not appear to favor the establishment of Fusarium spp. in onychomycosis. © 2014 S. Karger AG, Basel.

  18. Synergistic anticandidal activity of menthol in combination with itraconazole and nystatin against clinical Candida glabrata and Candida krusei isolates.

    Science.gov (United States)

    Sharifzadeh, Aghil; Khosravi, Ali Reza; Shokri, Hojjatollah; Tari, Paria Samadi

    2017-06-01

    Candida glabrata (C. glabrata) and C. krusei are now emerging as serious hospital acquired infections in immunocompromised patients. Menthol, a terpenic compound, has been reported to have antifungal activity. The aim of this study was to investigate the effect of menthol in combination with itraconazole or nystatin against C. glabrata and C. krusei isolates. The effects of menthol along with itraconazole and nystatin, were evaluated by the Clinical Laboratory Standards Institute (CLSI) M44-A and CLSI M27-A3 methods. The fractional inhibitory concentration index (FICI) was determined for menthol plus itraconazole and nystatin combinations using the checkerboard method. The mean of minimum inhibitory concentration (MIC) values of menthol, nystatin and itraconazole were 53.2, 2.30 and 1.50 μg/ml for C. glabrata isolates and 121, 1.08 and 0.38 μg/ml for C. krusei isolates, respectively. Menthol in combination with itraconazole or nystatin exhibited the synergistic effects against all species of Candida tested. FICI values for menthol plus itraconazole and nystatin combinations ranged from 0.250 to 0.561 and 0.139 to 0.623 for C. glabrata isolates, and 0.182 to 0.750 and 0.188 to 0.760 for C. krusei, respectively. These results support the potential use of menthol as an anticandidal agent, and it can be used complementarily with other conventional antifungal agents. Copyright © 2017. Published by Elsevier Ltd.

  19. Formulation and In Vitro Characterization of Thiolated Buccoadhesive Film of Fluconazole.

    Science.gov (United States)

    Naz, Kiran; Shahnaz, Gul; Ahmed, Naveed; Qureshi, Naveeda Akhtar; Sarwar, Hafiz Shoaib; Imran, Muhammad; Khan, Gul Majid

    2017-05-01

    The present work is focused on the development of thiolated film for fluconazole buccal delivery. To this end, unmodified polymers chitosan and sodium carboxymethylcellulose (NaCMC) backbone was covalently modified by thioglycolic acid (TGA) and cysteine, respectively. The thiolated buccoadhesive film was evaluated in terms of thickness, weight uniformity, water-uptake capacity, drug content, and release patterns. Moreover, mucoadhesion profile was investigated on buccal mucosa. The resulting chitosan-TGA and NaCMC-cysteine conjugates displayed 171 ± 13 and 380 ± 19 μmol thiol groups per gram of polymer (mean ± SD; n = 3), respectively. The water binding capacity of the thiolated film was significantly ∼2-fold higher (p thiolated film displayed 5.8-fold higher mucoadhesive properties compared with corresponding film. Controlled release of drugs from film was observed over 8 h. The transport of fluconazole across excised buccal mucosa was enhanced up to 17-fold in comparison with fluconazole applied in buffer. Based on these findings, thiolated film seems to be promising for fluconazole buccal delivery.

  20. Voriconazole versus amphotericin B or fluconazole in cancer patients with neutropenia

    DEFF Research Database (Denmark)

    Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Dalbøge, Christina S

    2014-01-01

    and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia. SEARCH METHODS: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE (to January 2014). Letters, abstracts and unpublished trials were...

  1. Assessment of Effectiveness of Fluconazole and Clotrimazole in Treating Oral Candidiasis Patients: A Comparative Study.

    Science.gov (United States)

    Reddy, R C Jagat; Jeelani, S; Duraiselvi, P; Kandasamy, M; Kumar, G Suresh; Pandian, R Azhal Vel

    2017-01-01

    One of the most common fungal infections infecting humans is Candidiasis. Belonging to the group of opportunistic infections, it often affects individuals with various debilitating diseases. Fluconazole and clotrimazole are two of the commonly used anti-fungal agents for the treatment of oral candidiasis. Hence, we planned this study to evaluate the effectiveness of fluconazole and clotrimazole in the treatment of patients suffering from candidiasis. A total of 180 participants were enrolled in the present study. All the patients of candidiasis were divided broadly into two study groups. Group I included patients who were treated with fluconazole mouthrinse whereas group II included patients who were treated with clotrimazole mouth paint. Grading of patient discomfort was done as noted from readings given by the patients. Specimen was collection by a swab from the lesional area of the oral cavity from the patients and were incubated in Sabouraud's dextrose agar medium and assessed. All the patients were treated with medication as give to their respective groups. Patients were recalled as assessed. All the readings were recorded and analyzed. For group I patients, the fungal eradication was 89.5%, whereas for group II patients, the fungal eradication was 86.7%. No significant results were obtained while comparing the mycological eradiation in patients of the two study groups. Approximately similar effectiveness in terms of treatment was noted with fluconazole and clotrimazole in treating patients with candidiasis.

  2. Solid-state characterization and impurities determination of fluconazol generic products marketed in Morocco

    Science.gov (United States)

    Bourichi, Houda; Brik, Youness; Hubert, Philipe; Cherrah, Yahia; Bouklouze, Abdelaziz

    2012-01-01

    In this paper, we report the results of quality control based in physicochemical characterization and impurities determination of three samples of fluconazole drug substances marketed in Morocco. These samples were supplied by different pharmaceuticals companies. The sample A, as the discovered product, was supplied by Pfizer, while samples B and C (generics), were manufactured by two different Indian industries. Solid-state characterization of the three samples was realized with different physicochemical methods as: X-ray powder diffraction, Fourier-transformation infrared spectroscopy, differential scanning calorimetry. High performance liquid chromatography was used to quantify the impurities in the different samples. The results from the physicochemical methods cited above, showed difference in polymorph structure of the three drug substances. Sample A consisted in pure polymorph III, sample B consisted in pure polymorph II, sample C consisted in a mixture of fluconazole Form III, form II and the monohydrate. This result was confirmed by differential scanning calorimetry. Also it was demonstrated that solvents used during the re-crystallization step were among the origins of these differences in the structure form. On the other hand, the result of the stability study under humidity and temperature showed that fluconazole polymorphic transformation could be owed to the no compliance with the conditions of storage. The HPLC analysis of these compounds showed the presence of specific impurities for each polymorphic form, and a possible relationship could be exist between impurities and crystalline form of fluconazole. PMID:29403776

  3. Risk of malformations and other outcomes in children exposed to fluconazole in utero

    DEFF Research Database (Denmark)

    Sørensen, Henrik Toft; Nielsen, Gunnar Lauge; Olesen, Charlotte

    1999-01-01

    Aim Fluconazole is an active drug systematically used in the oral treatment of vaginal candidiasis and other fungal diseases. We examined the risk of malformations and other birth outcomes following pregnancy related exposures. Method From 1 January 1991 to 31 December 1996 we identified 165 women...

  4. Possible mechanisms of the antifungal activity of fluconazole in combination with terbinafine against Candida albicans.

    Science.gov (United States)

    Khodavandi, Alireza; Alizadeh, Fahimeh; Vanda, Nasim Aghai; Karimi, Golgis; Chong, Pei Pei

    2014-12-01

    Candidiasis is a term describing infections by yeasts from the genus Candida, the majority Candida albicans. Treatment of such infections often requires antifungals such as the azoles, but increased use of these drugs has led to selection of yeasts with increased resistance to these drugs. Combination therapy would be one of the best strategies for the treatment of candidiasis due to increased resistance to azoles. The antifungal activities of fluconazole and terbinafine were evaluated in vitro alone and in combination using broth microdilution test and time kill study. Eventually the expression level of selected genes involved in ergosterol biosynthesis of Candida was evaluated using semi-quantitative RT-PCR. The obtained results showed the significant MICs ranging from 0.25 to 8 µg/mL followed by FICs ranged from 0.37 to 1 in combination with fluconazole/terbinafine. Our findings have demonstrated that the combination of fluconazole and terbinafine could also significantly reduce the expression of ERG1, 3, and 11 in the cell membrane of Candida in all concentrations tested ranging from 1.73- to 6.99-fold. This study was undertaken with the ultimate goal of finding the probable targets of fluconazole/terbinafine in C. albicans by looking at its effects on cell membrane synthesis.

  5. Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering

    KAUST Repository

    Kuo, Dwight; Tan, Kai; Zinman, Guy; Ravasi, Timothy; Bar-Joseph, Ziv; Ideker, Trey

    2010-01-01

    Background: Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure. Results: Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither, leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity. Conclusions: We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways.

  6. Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering

    KAUST Repository

    Kuo, Dwight

    2010-07-23

    Background: Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure. Results: Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither, leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity. Conclusions: We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways.

  7. Outbreak of candidemia caused by fluconazole resistant Candida parapsilosis strains in an intensive care unit.

    Science.gov (United States)

    Pinhati, Henrique Marconi Sampaio; Casulari, Luiz Augusto; Souza, Ana Carolina Remondi; Siqueira, Ricardo Andreotti; Damasceno, Camila Maria Gomes; Colombo, Arnaldo Lopes

    2016-08-20

    Candidemia is an increasing problem in tertiary care hospitals worldwide. Here, we report the first outbreak of candidemia caused by fluconazole-resistant C. parapsilosis (FRCP) strains in Brazil. This was a cross-sectional study of clinical and microbiological data of all candidemic episodes diagnosed from July 2011 to February 2012 in a 200-bed tertiary care hospital. Initial yeast identification and susceptibility testing were performed using the VITEK 2 - System. Isolates of Candida spp. resistant to fluconazole were sent to a reference laboratory (LEMI-UNIFESP) for further molecular identification and confirmation of resistance by CLSI microdilution test. A multivariate analysis was conducted to identify factors associated with FRCP infection. We identified a total of 40 critically ill patients with candidemia (15 women) with a median age of 70 years. The incidence of candidemia was 6 cases/1,000 patients admissions, including 28 cases (70 %) of infection with C. parapsilosis, 21 of which (75 %) were resistant to fluconazole. In only 19 % of FRCP candidemia cases had fluconazole been used previously. The results of our study indicated that diabetes is a risk factor for FRCP candidemia (p = 0.002). Overall, mortality from candidemia was 45 %, and mortality from episodes of FRCP infections was 42.9 %. The clustering of incident cases in the ICU and molecular typing of strains suggest horizontal transmission of FRCP. Accurate vigilant monitoring for new nosocomial strains of FRCP is required.

  8. Synthesis of sup 18 F-labeled fluconazole and positron emission tomography studies in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Livni, E. (Massachusetts General Hospital, Boston, MA (United States). Dept. of Radiology); Fischman, A.J. (Massachusetts General Hospital, Boston, MA (United States). Radiology Dept. Havard Medical School, Boston, MA (United States). Dept. of Radiology Havard Medical School, Boston, MA (United States). Dept. of Medicine)

    1992-02-01

    (4-{sup 18}F) 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propanol ((4-{sup 18}F) fluconazole) was synthesized from its amino precursor. Fieldel-Crafts acylation of 3-fluoroacetanilide with chloroacetyl chloride produced 2'-fluoro-4'-aceteamido-2-(1H-1,2,4-triazole-1-yl) acetophenone in 12% yield. Sequential reaction with (1) dimethylsulphoxonium methylide and (2) 1,2,4-triazole followed by in situ hydrolysis resulted in 2-(2-fluoro-4-aminophenyl)-1,3-bis(1H-2,2,4-triazol-1-yl)-2-propanol in 19% yield. A modified Schiemann reaction on this product resulted in (4-{sup 18}F)fluconazole with a radiochemical yield of 1.0-2.0% (EOS) within 2h. (4-{sup 18}F)Fluconazole was used to measure the pharmacokinetics of fluconazole in rats by measurement of radioactivity in excised tissues and in rabbits by PET. In both species, there was rapid equilibration of (4-{sup 18}F)fluoconazole to a relatively uniform distribution of radioactivity in most organs. (Author).

  9. Clinical Validation of the Analysis of Fluconazole in Oral Fluid in Hospitalized Children

    NARCIS (Netherlands)

    van der Elst, Kim C. M.; van Alst, Manouche; Lub-de Hooge, Marjolijn N.; van Hateren, Kai; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.; Scholvinck, Elisabeth H.

    2014-01-01

    Fluconazole is a first-line antifungal agent for the treatment and prophylaxis of invasive candidiasis in pediatric patients. Pediatric patients are at risk of suboptimal drug exposure, due to developmental changes in gastrointestinal and renal function, metabolic capacity, and volume of

  10. The effect of fluconazole on ritonavir and saquinavir pharmacokinetics in HIV-1-infected individuals

    NARCIS (Netherlands)

    Koks, C. H.; Crommentuyn, K. M.; Hoetelmans, R. M.; Burger, D. M.; Koopmans, P. P.; Mathôt, R. A.; Mulder, J. W.; Meenhorst, P. L.; Beijnen, J. H.

    2001-01-01

    To study the effect of fluconazole on the steady-state pharmacokinetics of the protease inhibitors ritonavir and saquinavir in HIV-1-infected patients. Five subjects treated with saquinavir and three with ritonavir received the protease inhibitor alone (saquinavir 1200 mg three times daily,

  11. Sporotrichosis by Sporothrix schenckii senso stricto with itraconazole resistance and terbinafine sensitivity observed in vitro and in vivo: Case report

    Directory of Open Access Journals (Sweden)

    Rodrigo Vettorato

    2018-03-01

    Full Text Available We report a case of a patient with lymphocutaneous sporotrichosis in the right upper limb. The fungus was identified as Sporothrix schenckii senso stricto by calmodulin gene sequencing. The initial treatment was itraconazole (200 mg/day, but in vitro antifungal susceptibility demonstrated high resistant to this and another six antifungals, with exception to terbinafine. The lesions did not regress with itraconazole treatment. Thus, 500 mg/day of terbinafine was prescribed and clinical cure was obtained after four months

  12. Physical state of poorly water soluble therapeutic molecules loaded into SBA-15 ordered mesoporous silica carriers: a case study with itraconazole and ibuprofen.

    Science.gov (United States)

    Mellaerts, Randy; Jammaer, Jasper A G; Van Speybroeck, Michiel; Chen, Hong; Van Humbeeck, Jan; Augustijns, Patrick; Van den Mooter, Guy; Martens, Johan A

    2008-08-19

    The ordered mesoporous silica material SBA-15 was loaded with the model drugs itraconazole and ibuprofen using three different procedures: (i) adsorption from solution, (ii) incipient wetness impregnation, and (iii) heating of a mixture of drug and SBA-15 powder. The location of the drug molecules in the SBA-15 particles and molecular interactions were investigated using nitrogen adsorption, TGA, DSC, DRS UV-vis, and XPS. The in vitro release of hydrophobic model drugs was evaluated in an aqueous environment simulating gastric fluid. The effectiveness of the loading method was found to be strongly compound dependent. Incipient wetness impregnation using a concentrated itraconazole solution in dichloromethane followed by solvent evaporation was most efficient for dispersing itraconazole in SBA-15. The itraconazole molecules were located on the mesopore walls and inside micropores of the mesopore walls. When SBA-15 was loaded by slurrying it in a diluted itraconazole solution from which the solvent was evaporated, the itraconazole molecules ended up in the mesopores that they plugged locally. At a loading of 30 wt %, itraconazole exhibited intermolecular interactions inside the mesopores revealed by UV spectroscopy and endothermic events traced with DSC. The physical mixing of itraconazole and SBA-15 powder followed by heating above the itraconazole melting temperature resulted in formulations in which glassy itraconazole particles were deposited externally on the SBA-15 particles. Loading with ibuprofen was successful with each of the three loading procedures. Ibuprofen preferably is positioned inside the micropores. In vitro release experiments showed fast release kinetics provided the drug molecules were evenly deposited over the mesoporous surface.

  13. Malformations Induced in Pregnant Rats and their Fetuses Treated with Fluconazole and / or Gamma Radiation

    International Nuclear Information System (INIS)

    Ramadan, F.L.

    2013-01-01

    The purpose of the present work is to study the synergistic effect of antifungal (fluconazole) treatment and / or g-radiation stress on pregnant mothers and their developing embryos by evaluating the maternal biochemical changes, embryological and histopathological lesions. Fluconazole is a broad-spectrum azole antifungal medication used for the treatment of several types of fungal infections including common forms such as vaginal candidiasis. Fluconazole (50 mg/kg b.wt.) was daily administered by oral gavage to pregnant rats from the 4th to the 13th gestational days during which they were subjected to g-radiation at a dose level of 1 Gy given at the 6th day (post implantation period) and 1 Gy on the 12th day (organogenesis period) of gestation. The animals were dissected and examined on the 20th day of gestation (one day prior to praturation). Fluconazole and radiation dual treatment resulted in increased maternal serum of lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transaminase (AST) activities and sodium (Na + ) level accompanied with a decline in potassium (K + ) concentration. The results showed that there was an elevation in the lipid peroxidation end product malondialdehyde (MDA) as well as nitric oxide (NO) in the brain and heart tissues of pregnant rats. Meantime, the developing embryos in the uteri showed various teratological, skeletal and histological impairments. Moreover, the fluconazole treatment and / or g-radiation harm effects were detected as growth retardation, malformations, intrauterine death and embryonic resorption. The examination of the endoskeletal system of fetuses showed retardation in the ossification of the skull bones and lack of ossification at the center of vertebrae and appendages. In addition, the embryonic histological examinations revealed heart loss of normal architecture, the interstitial tissues were oedematous and containing necrotic cellular debris together with fibrosis of nerve cells in the brain

  14. Atypical Clinical Presentation of Sporotrichosis Caused by Sporothrix globosa Resistant to Itraconazole.

    Science.gov (United States)

    Fischman Gompertz, Olga; Rodrigues, Anderson M; Fernandes, Geisa F; Bentubo, Henri D L; de Camargo, Zoilo Pires; Petri, Valéria

    2016-06-01

    Sporotrichosis is a polymorphic disease of humans and animals, which is acquired via traumatic inoculation of Sporothrix propagules into cutaneous or subcutaneous tissue. The etiological agents are in a clinical complex, which includes Sporothrix brasiliensis, Sporothrix schenckii, Sporothrix globosa, and Sporothrix luriei, each of which has specific epidemiological and virulence characteristics. Classical manifestation in humans includes a fixed localized lesion at the site of trauma plus lymphocutaneous sporotrichosis with fungal spreading along the lymphatic channels. Atypical sporotrichosis is a challenge to diagnosis because it can mimic many other dermatological diseases. We report an unusual, itraconazole-resistant cutaneous lesion of sporotrichosis in a 66-year-old Brazilian man. Histopathological examination of the skin revealed vascular and fibroblastic proliferation with chronic granulomatous infiltrate composed of multinucleated giant cells. Sporothrix were isolated from the skin lesion, and phylogenetic analyses confirmed it to be sporotrichosis due to S. globosa, a widespread pathogen. Immunoblotting analysis showed several IgG-reactive molecules in autochthonous preparations of the whole cellular proteins (160, 80, 60, 55, 46, 38, 35, and 30 kDa) and exoantigen (35 and 33 kDa). The patient was first unsuccessfully treated with daily itraconazole, and then successfully treated with potassium iodide. © The American Society of Tropical Medicine and Hygiene.

  15. Reduced itraconazole concentration and durations are successful in treating Batrachochytrium dendrobatidis infection in amphibians.

    Science.gov (United States)

    Brannelly, Laura A

    2014-03-14

    Amphibians are experiencing the greatest decline of any vertebrate class and a leading cause of these declines is a fungal pathogen, Batrachochytrium dendrobatidis (Bd), which causes the disease chytridiomycosis. Captive assurance colonies are important worldwide for threatened amphibian species and may be the only lifeline for those in critical threat of extinction. Maintaining disease free colonies is a priority of captive managers, yet safe and effective treatments for all species and across life stages have not been identified. The most widely used chemotherapeutic treatment is itraconazole, although the dosage commonly used can be harmful to some individuals and species. We performed a clinical treatment trial to assess whether a lower and safer but effective dose of itraconazole could be found to cure Bd infections. We found that by reducing the treatment concentration from 0.01-0.0025% and reducing the treatment duration from 11-6 days of 5 min baths, frogs could be cured of Bd infection with fewer side effects and less treatment-associated mortality.

  16. Rapid method for the analysis of itraconazole and hydroxyitraconazole in serum by high-performance liquid chromatography

    NARCIS (Netherlands)

    Compas, D; Touw, D J; de Goede, P N

    1996-01-01

    An assay for the determination of itraconazole and its active metabolite hydroxyitraconazole in serum has been developed, using ketoconazole as internal standard. The procedure involved a one-step liquid-liquid extraction of the drug, its metabolite and the internal standard, followed by their

  17. Comparison of two systemic antifungal agents, itraconazole and terbinafine, for the treatment of dermatophytosis in European hedgehogs (Erinaceus europaeus).

    Science.gov (United States)

    Bexton, Steve; Nelson, Helen

    2016-12-01

    Dermatophytosis caused by Trichophyton erinacei is a common scaling and crusting skin disease affecting European hedgehogs (Erinaceus europaeus) admitted to wildlife rescue centres. The application of topical therapy can be challenging because wild hedgehogs are subject to stress and often roll into a ball when handled. Systemic antifungal therapy is more convenient but has not been evaluated in this species. To compare the efficacy of oral itraconazole versus oral terbinafine for the treatment of dermatophytosis affecting hedgehogs. A treatment trial was undertaken in a wildlife hospital involving 165 hedgehogs with naturally occurring dermatophytosis. Animals were randomly divided into two groups and treated with either itraconazole or terbinafine orally for 28 days. The therapeutic efficacy was evaluated after 14 and 28 days by mycological culture and clinical dermatological lesion scores. Both drugs were well tolerated and clinically effective. After 14 and 28 days of treatment, the respective mycological cure rate was 36.6% and 65.9% for the itraconazole-treated group and 92.8% and 98.8% for the terbinafine-treated group. Itraconazole and terbinafine were both effective for the treatment of dermatophytosis affecting hedgehogs; however, terbinafine was more effective. © 2016 ESVD and ACVD.

  18. Plasma Concentrations of Itraconazole, Voriconazole, and Terbinafine When Delivered by an Impregnated, Subcutaneous Implant in Japanese Quail ( Coturnix japonica ).

    Science.gov (United States)

    Souza, Marcy J; Redig, Patrick; Cox, Sherry K

    2017-06-01

    Aspergillosis is a common fungal infection in both wild and pet birds. Although effective antifungal medications are available, treatment of aspergillosis can require months of medication administration, which entails stressful handling one or more times per day. This study examined the delivery of the antifungal drugs itraconazole, voriconazole, and terbinafine to Japanese quail ( Coturnix japonica ) via an impregnated implant. Implants contained 0.5, 3, 8, or 24 mg of itraconazole, voriconazole, or terbinafine. The implants were administered subcutaneously over the dorsum and between the scapulae. Blood was collected from birds before and 2, 7, 21, 42, and 56 days after implant placement. Plasma was analyzed by high-performance liquid chromatography for concentrations of itraconazole, voriconazole, or terbinafine, as appropriate. During the course of the study, targeted terbinafine concentrations were achieved in some birds at various time points, but concentrations were inconsistent. Itraconazole and voriconazole concentrations were also inconsistent and did not reach targeted concentrations. Currently, the implant examined in this study cannot be recommended for treatment of aspergillosis in avian species.

  19. Treatment of Chagas' disease with itraconazole: electrocardiographic and parasitological conditions after 20 years of follow-up.

    Science.gov (United States)

    Apt, Werner; Arribada, Arturo; Zulantay, Inés; Rodríguez, Jorge; Saavedra, Miguel; Muñoz, Andrea

    2013-09-01

    To evaluate cases of chronic Chagas' disease for the long-term effects of treatment with itraconazole on Trypanosoma cruzi infections and the regression or development of ECG abnormalities. In March 1992, we treated 46 patients with chronic Chagas' disease with 6 mg/kg/day of itraconazole for 120 days in a blind evaluation. The patients came from an area of Chile where the disease was endemic and were checked for ECG abnormalities and with xenodiagnosis (XD) or real-time XD-quantitative PCR (XD-qPCR) for Trypanosoma cruzi infection before treatment and once a year for 20 years. Twenty-one patients proved to be uninfected after 20 years and 15 of the patients had a normal ECG. Of the latter cases, 32.6% could be considered cured, although all of them had positive serology. Itraconazole prevents the development of ECG abnormalities, because after 20 years of treatment only 10.86% of patients developed ECG abnormalities (Z = 1.70, P = 0.046). XD-qPCR performed on 16 patients demonstrated 10 cases with XD; these cases correspond to therapy failure, since re-infection was ruled out. In one case, XD-qPCR did not present amplification. Itraconazole is useful in the treatment of chronic Chagas' disease as it prevented the development of ECG abnormalities and cured 32.6% of patients.

  20. Fluconazole Resistance Associated with Drug Efflux and Increased Transcription of a Drug Transporter Gene, PDH1, in Candida glabrata

    Science.gov (United States)

    Miyazaki, Haruko; Miyazaki, Yoshitsugu; Geber, Antonia; Parkinson, Tanya; Hitchcock, Christopher; Falconer, Derek J.; Ward, Douglas J.; Marsden, Katherine; Bennett, John E.

    1998-01-01

    Sequential Candida glabrata isolates were obtained from the mouth of a patient infected with human immunodeficiency virus type 1 who was receiving high doses of fluconazole for oropharyngeal thrush. Fluconazole-susceptible colonies were replaced by resistant colonies that exhibited both increased fluconazole efflux and increased transcripts of a gene which codes for a protein with 72.5% identity to Pdr5p, an ABC multidrug transporter in Saccharomyces cerevisiae. The deduced protein had a molecular mass of 175 kDa and was composed of two homologous halves, each with six putative transmembrane domains and highly conserved sequences of ATP-binding domains. When the earliest and most azole-susceptible isolate of C. glabrata from this patient was exposed to fluconazole, increased transcripts of the PDR5 homolog appeared, linking azole exposure to regulation of this gene. PMID:9661006

  1. Candida species distribution and fluconazole susceptibility of blood isolates at a regional hospital in Passo Fundo, RS, Brazil

    Directory of Open Access Journals (Sweden)

    Maira Giseli C. Silva

    2015-06-01

    Full Text Available ABSTRACT Introduction: Candidemia is a bloodstream infection produced by Candida genus yeasts. Objective: The purpose of this study was to characterize the epidemiology and the fluconazole susceptibility in Candida species isolated from patients at a regional hospital in Passo Fundo, RS. Methods: Records from the laboratory were used to identify patients with positive blood cultures for Candida between 2010 and 2011. The in vitro activity of fluconazole was determined using the disk diffusion method. Results: Were analyzed 24 positive blood cultures for Candida and found a 54.16% mortality rate. C. albicans was the most prevalent species, followed by C. parapsilosis and C. krusei. For susceptibility to fluconazole, C. albicans, C. parapsilosis and C. tropicalis showed 100% sensitivity. However, C. krusei was 100% resistant; and C. glabrata, 50% resistant. Conclusion: The high mortality and fluconazole resistance rates emphasize the importance of the diagnosis of candidemia in a hospital environment.

  2. Antifungal mechanism of the combination of Cinnamomum verum and Pelargonium graveolens essential oils with fluconazole against pathogenic Candida strains.

    Science.gov (United States)

    Essid, Rym; Hammami, Majdi; Gharbi, Dorra; Karkouch, Ines; Hamouda, Thouraya Ben; Elkahoui, Salem; Limam, Ferid; Tabbene, Olfa

    2017-09-01

    The present study aimed to investigate the anti-Candida activity of ten essential oils (EOs) and to evaluate their potential synergism with conventional drugs. The effect on secreted aspartic protease (SAP) activity and the mechanism of action were also explored. The antifungal properties of essential oils were investigated using standard micro-broth dilution assay. Only Cinnamomum verum, Thymus capitatus, Syzygium aromaticum, and Pelargonium graveolens exhibited a broad spectrum of activity against a variety of pathogenic Candida strains. Chemical composition of active essential oils was performed by gas chromatography-mass spectrometry (GC-MS). Synergistic effect was observed with the combinations C. verum/fluconazole and P. graveolens/fluconazole, with FIC value 0.37. Investigation of the mechanism of action revealed that C. verum EO reduced the quantity of ergosterol to 83%. A total inhibition was observed for the combination C. verum/fluconazole. However, P. graveolens EO may disturb the permeability barrier of the fungal cell wall. An increase of MIC values of P. graveolens EO and the combination with fluconazole was observed with osmoprotectants (sorbitol and PEG6000). Furthermore, the combination with fluconazole may affect ergosterol biosynthesis and disturb fatty acid homeostasis in C. albicans cells as the quantity of ergosterol and oleic acid was reduced to 52.33 and 72%, respectively. The combination of P. graveolens and C. verum EOs with fluconazole inhibited 78.31 and 64.72% SAP activity, respectively. To our knowledge, this is the first report underlying the mechanism of action and the inhibitory effect of SAP activity of essential oils in synergy with fluconazole. Naturally occurring phytochemicals C. verum and P. graveolens could be effective candidate to enhance the efficacy of fluconazole-based therapy of C. albicans infections.

  3. The expression of genes involved in the ergosterol biosynthesis pathway in Candida albicans and Candida dubliniensis biofilms exposed to fluconazole.

    LENUS (Irish Health Repository)

    2009-03-01

    The expression of the ERG1, ERG3, ERG7, ERG9, ERG11 and ERG25 genes in response to incubation with fluconazole and biofilm formation was investigated using reverse-transcription PCR and real-time PCR in Candida albicans and Candida dubliniensis clinical isolates. The viability of biofilm was measured using an 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay and confocal scanning laser microscopy (CSLM). Expression of the ERG11 gene was found to be low or moderate and it was regulated by fluconazole addition more so than by biofilm formation. Very low or non-detectable expression of ERG1, ERG7 and ERG25 genes was detected in C. albicans. The expression of the ERG9 increased in the presence of fluconazole in some isolates. Following incubation with fluconazole, formation of biofilm by C. dubliniensis was coupled with up-regulation of the ERG3 and ERG25 genes as have been observed previously in C. albicans. Planktonic cells of both Candida species released from biofilm displayed similar resistance mechanisms to fluconazole like attached cells. The XTT reduction assay and CSLM revealed that although incubation with fluconazole decreased the biofilm thickness, these were still comprised metabolically active cells able to disseminate and produce biofilm. Our data indicate that biofilm represents a highly adapted community reflecting the individuality of clinical isolates.

  4. Puerperal brain cryptococcoma in an HIV-negative woman successfully treated with fluconazole: a case report

    Directory of Open Access Journals (Sweden)

    José Edward Hagan

    2014-04-01

    Full Text Available Cryptococcus spp. cerebral abscesses are uncommon in immunocompetent subjects. The recommended induction treatment is the administration of amphotericin B plus flucytosine combined with resection for lesions ≥3cm. In this paper, we describe an HIV-negative woman diagnosed with a large cryptococcoma in the immediate postpartum period. The lesion was not resected, and due to amphotericin B intolerance, she received an extended course of fluconazole monotherapy. There was no disease recurrence during the 4 years of follow-up. The abrupt onset of her symptoms following delivery suggests that she developed a postpartum immune reconstitution syndrome. This case also demonstrates that in specific situations fluconazole monotherapy can be attempted in immunocompetent patients with cryptococcoma.

  5. Effects of Membrane PEGylation on Entry and Location of Antifungal Drug Itraconazole and Their Pharmacological Implications

    DEFF Research Database (Denmark)

    Dzieciuch-Rojek, Monika; Poojari, Chetan; Bednar, Jan

    2017-01-01

    Itraconazole (ITZ) is an antifungal agent used clinically to treat mycotic infections. However, its therapeutic effects are limited by low solubility in aqueous media. Liposome-based delivery systems (LDS) have been proposed as a delivery mechanism for ITZ to alleviate this problem. Furthermore...... of ITZ incorporation into liposomes both with and without PEGylation because it can provide a potential foundation for the rational design of LDS-based systems for delivery of ITZ, using alternate protective polymers or formulations. Here we have combined atomistic simulations, cryo-TEM, Langmuir film...... balance, and fluorescence quenching experiments to explore how ITZ interacts with both pristine and PEGylated liposomes. We found that the drug can be incorporated into conventional and PEGylated liposomes for drug concentrations up to 15 mol % without phase separation. We observed that, in addition...

  6. Malassezia pachydermatis fungemia in a preterm neonate resistant to fluconazole and flucytosine

    Directory of Open Access Journals (Sweden)

    Noura Al-Sweih

    2014-07-01

    Full Text Available A case of Malassezia pachydermatis fungemia in a preterm neonate is described. The isolate was identified by rDNA sequencing and was resistant to fluconazole and flucytosine. Since M. pachydermatis does not require lipid supplementation for growth, it can be misidentified as a Candida species. The report highlights M. pachydermatis as a cause of late onset sepsis in preterm neonates and emphasizes the need for prior antifungal susceptibility testing.

  7. Speciation of Candida using chromogenic and cornmeal agar with determination of fluconazole sensitivity

    OpenAIRE

    Saroj Golia; K. Mallika Reddy; K. Sujatha Karjigi; Vivek Hittinahalli

    2013-01-01

    Objective and background: Candidiasis is an important cause of fungal infections. This study was carried out to determine the species incidence using chrom agar & cornmeal agar, susceptibility pattern to fluconazole by microbroth dilution methods of yeasts isolated from the clinical samples. Method: Positive samples for candidiasis where collected from 112 patients at Dr B R AMC from April 2010 to April 2011, processed by routine methods, chrom agar media and corn meal agar was used to spec...

  8. The development of Cutina lipogels and gel microemulsion for topical administration of fluconazole

    OpenAIRE

    Ellaithy, H. M.; El-Shaboury, K. M. F.

    2002-01-01

    The influence of the vehicle on the release and permeation of fluconazole, a topical antifungal drug dissolved in Jojoba oil was evaluated. Series of Cutina lipogels (Cutina CPA [cetyl palmitate], CBS [mixture of glyceryl stearate, cetearyl alcohol, cetyl palmitate, and cocoglycerides], MD [glyceryl stearate], and GMS [glyceryl monostearate]) in different concentrations as well as gel microemulsion were prepared. In-vitro drug release in Sorensens citrate buffer (pH 5.5) and permeation throug...

  9. The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis.

    Science.gov (United States)

    Zhou, Xiaofang; Li, Ting; Fan, Shangrong; Zhu, Yuxia; Liu, Xiaoping; Guo, Xuedong; Liang, Yiheng

    2016-07-01

    To compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7-14 follow-up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30-35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7-14 follow-up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30-35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder. © 2016 The Authors Mycoses Published by Blackwell Verlag GmbH.

  10. Interspecies differences of candida species causing recurrent vulvovaginal candidiasis in response to fluconazole treatment

    Directory of Open Access Journals (Sweden)

    Siamak Naji

    2017-07-01

    Methods: The cross-sectional study was performed at Kowsar Gynecology Center, Motahhari educational hospital and Medical Mycology Center, Faculty of Medicine, Urmia, Iran, from October 2013 to July 2015. Those patients referred to the clinic with symptoms of vaginal discharge, itching or burning that swab samples from endo-exocervix and distal fornix discharge were taken. The vaginal discharge samples submitted to Medical Mycology Center, Urmia School of Medicine for the direct microscopic examination and cultures. Identification at the level of species was performed using CHROMagar Candida and Corn meal agar media. The molecular test polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP used for confirming culture results. For the susceptibility assay, disc diffusion method was performed with fluconazole and clotrimazole. Results: In these study 198 samples collected from patients with symptoms of vulvovaginal candidiasis, 77 vulvovaginal candidiasis cases were identified. Candida species are common in primary and recurrent cases in terms of frequency, Candida albicans (85.7%, Candida krusei (10.2% and Candida glabrata (4.1% were identified respectively. Total of 27 cases of recurrent vulvovaginal candidiasis, 10 cases were resistant to both clotrimazole and fluconazole (37% was observed that the most common species are resistant to treatment were Candida albicans by (82.1%, Candida krusei (14.3% and Candida glabrata (3.6% respectively. Drug resistance in Candida albicans, Candida krusei and Candida glabrata causing recurrent vulvovaginal candidiasis included 69.1%, 75% and 100% respectively. Conclusion: Our findings have shown frequency of resistant non-albicans Candida species to fluconazole and clotrimazole is increasing. There is a considerable difference between Candida albicans and non-albicans species, Candida glabrata for the resistance to fluconazole and clotrimazole.

  11. Single and multiple dose Fluconazole in the treatment of candidia vulvovaginitis: a prospective comparative study

    Directory of Open Access Journals (Sweden)

    Ashrafinia M

    2007-09-01

    Full Text Available  Background: Vulvovaginal candidiasis, the most common type of vaginitis, is usually caused by Candidia albicans. Patients experience a variety of symptoms. There are many types of vulvovaginal candidiasis with various microbial causes, symptoms, host circumstances, recurrence rates, and responses to treatment. The purpose of this study was to find the best method of treatment of complicated vaginitis as determined by its high prevalence, varying symptoms and signs and patient complaints.Methods: In this open clinical trial without placebo control, we studied all patients aged 18 to 65 years, suffering from vaginitis symptoms that presented at the gynecological clinic of Arash Hospital, Tehran, Iran, during the year 2004. After obtaining informed consent, we assessed the response to a treatment of single 150 mg dose of fluconazole in one group, and sequential 150 mg doses of fluconazole in the other. The analysis was performed using SPSS statistical software (version 11.Results: With regard to symptom severity, no significant difference was found between the groups. The rate of excoriation and fissure formation demonstrated significant difference between the two groups (p=0.048. Assessment of clinical and mycological response proved that patients with severe vaginitis treated with sequential doses of fluconazole had a better general status than those in the other group. The difference between the severity of vaginitis and positive response to the treatment in culture was not significant among patients with recurrent vaginitis.Conclusion: Patients with mild to moderate recurrent vaginitis show better response to treatment. The high rate of positive culture on day 35 reconfirms the limitation of fluconazole and other azoles as fungistatic drugs.

  12. Pharmacokinetics of fluconazole following intravenous and oral administration to koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Black, L A; Krockenberger, M B; Kimble, B; Govendir, M

    2014-02-01

    Clinically normal koalas (n = 12) received a single dose of 10 mg/kg fluconazole orally (p.o.; n = 6) or intravenously (i.v.; n = 6). Serial plasma samples were collected over 24 h, and fluconazole concentrations were determined using a validated HPLC assay. A noncompartmental pharmacokinetic analysis was performed. Following i.v. administration, median (range) plasma clearance (CL) and steady-state volume of distribution (Vss ) were 0.31 (0.11-0.55) L/h/kg and 0.92 (0.38-1.40) L/kg, respectively. The elimination half-life (t1/2 ) was much shorter than in many species (i.v.: median 2.25, range 0.98-6.51 h; p.o.: 4.69, range 2.47-8.01 h), and oral bioavailability was low and variable (median 0.53, range 0.20-0.97). Absorption rate-limited disposition was evident. Plasma protein binding was 39.5 ± 3.5%. Although fluconazole volume of distribution (Varea ) displayed an allometric relationship with other mammals, CL and t1/2 did not. Allometrically scaled values were approximately sevenfold lower (CL) and sixfold higher (t1/2 ) than observed values, highlighting flaws associated with this technique in physiologically distinct species. On the basis of fAUC/MIC pharmacodynamic targets, fluconazole is predicted to be ineffective against Cryptococcus gattii in the koala as a sole therapeutic agent administered at 10 mg/kg p.o. every 12 h. © 2013 John Wiley & Sons Ltd.

  13. Assay of fluconazole by high-performance liquid chromatography with a mixed-phase column.

    OpenAIRE

    Wallace, J E; Harris, S C; Gallegos, J; Foulds, G; Chen, T J; Rinaldi, M G

    1992-01-01

    A mixed-phase liquid chromatographic column was used to assay fluconazole in plasma, serum, and cerebrospinal fluid. The assay was linear from 0.2 to 20 micrograms/ml, with an average coefficient of variation of less than 5%. The partitioning of the drug between serum and cerebrospinal fluid was determined for 34 patients. The method was demonstrated to be suitable for both pharmacokinetic studies and monitoring of patients receiving treatment with this antifungal agent.

  14. Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

    Science.gov (United States)

    Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-12-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

    Science.gov (United States)

    van der Elst, Kim C. M.; Span, Lambert F. R.; van Hateren, Kai; Vermeulen, Karin M.; van der Werf, Tjip S.; Greijdanus, Ben; Kosterink, Jos G. W.; Uges, Donald R. A.

    2013-01-01

    Invasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P = 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling. PMID:23896473

  16. In vitro susceptibility testing of Aspergillus spp. against voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin.

    Science.gov (United States)

    Shi, Jun-yan; Xu, Ying-chun; Shi, Yi; Lü, Huo-xiang; Liu, Yong; Zhao, Wang-sheng; Chen, Dong-mei; Xi, Li-yan; Zhou, Xin; Wang, He; Guo, Li-na

    2010-10-01

    During recent years, the incidence of serious infections caused by opportunistic fungi has increased dramatically due to alterations of the immune status of patients with hematological diseases, malignant tumors, transplantations and so forth. Unfortunately, the wide use of triazole antifungal agents to treat these infections has lead to the emergence of Aspergillus spp. resistant to triazoles. The present study was to assess the in vitro activities of five antifungal agents (voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin) against different kinds of Aspergillus spp. that are commonly encountered in the clinical setting. The agar-based Etest MIC method was employed. One hundred and seven strains of Aspergillus spp. (5 species) were collected and prepared according to Etest Technique Manuel. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 hours at 35°C. MIC(50), MIC(90) and MIC range were acquired by Whonet 5.4 software. The MIC(90) of caspofungin against A. fumigatus, A. flavus and A. nidulans was 0.094 µg/ml whereas the MIC(90) against A. niger was 0.19 µg/ml. For these four species, the MIC(90) of caspofungin was the lowest among the five antifungal agents. For A. terrus, the MIC(90) of posaconazole was the lowest. For A. fumigatus and A. flavus, the MIC(90) in order of increasing was caspofungin, posaconazole, voriconazole, itraconazole, and amphotericin B. The MIC of amphotericin B against A. terrus was higher than 32 µg/ml in all 7 strains tested. The in vitro antifungal susceptibility test shows the new drug caspofungin, which is a kind of echinocandins, has good activity against the five species of Aspergillus spp. and all the triazoles tested have better in vitro activity than traditional amphotericin B.

  17. Combination of CuO nanoparticles and fluconazole: preparation, characterization, and antifungal activity against Candida albicans

    Energy Technology Data Exchange (ETDEWEB)

    Weitz, Iris S., E-mail: irisweitz@braude.ac.il; Maoz, Michal; Panitz, Daniel [ORT Braude College, Department of Biotechnology Engineering (Israel); Eichler, Sigal; Segal, Ester [Technion – Israel Institute of Technology, Department of Biotechnology and Food Engineering (Israel)

    2015-08-15

    Combination therapy becomes an important strategy in the management of invasive fungal infections and emergence of resistant fungi mutants. In this work, we examine the combination of copper oxide (CuO) nanoparticles (NPs) with fluconazole as potential treatment against the pathogenic fungi, Candidaalbicans. CuO NPs (∼7 nm in size) were synthesized with acetate ligands assembled on their surface, as shown by both thermal gravimetric analysis and FTIR spectroscopy. Unlike the commercial CuO (both bulk and 50 nm particles), that are poorly dispersed in water, the interaction with water allows the fine dispersion of the coated CuO NPs and their excellent colloidal stability. The addition of fluconazole to the aqueous CuO dispersion induced spontaneous self-assembly of the NPs into linear pearl-like chains network, shown by cryogenic transmission electron microscopy (cryo-TEM). The antifungal activity of the CuO NPs and their combination with fluconazole (fluconazole–CuO NPs) was studied against C. albicans. The best MIC values were obtained at concentrations as low as 0.2 and 0.3 mg/mL, respectively. The results suggest that fluconazole–CuO NPs can provide a potential alternative treatment for C. albicans infections.

  18. [Treatment of chronic recurrent vulvovaginal candidiasis with fluconazole (fungolon--Actavis)].

    Science.gov (United States)

    Borisov, I; Kolarov, G; Bobcheva, S; Ivanova, A

    2005-01-01

    The object of the study was to evaluate the efficacy of peroral administration of Fluconazole (Fungolon caps. 50 mg - "Actavis") in dose 150 mg (3 caps. x 50 mg) once weekly for a period of 6 months. 50 female patients of reproductive age with chronic vulvovaginal candidiasis caused by C. albicans with three or more recurrences per year were enrolled in an open trial prospective study and 42 women were evaluated before and after treatment. Clinical improvement was observed in 81% of the patients after treatment Microbiological cure was observed in 86% of the patients (36/42). Positive cultures for C. albicans after treatment had 6 patients. Four of these 6 patients had duration of the chronic candidiasis for more than 3 years. Side effects during the treatment were not significant and might not be directly correlated with the administration of fluconazole. There was no cessation of therapy due to side effects. 53.3% of the patients accepted positively the long duration of therapy while 30% found the long duration of treatment a major inconvenience. Fluconazole is easily administrated well tolerated and is suitable for the long treatment of chronic vulvovaginal candididasis.

  19. Exploration of crystal simulation potential by fluconazole isomorphism and its application in improvement of pharmaceutical properties

    Science.gov (United States)

    Thakur, Amitha; Kumar, Dinesh; Thipparaboina, Rajesh; Shastri, Nalini R.

    2014-11-01

    Control of crystal morphology during crystallization is a paramount challenge in pharmaceutical processing. Hence, there is need to introduce computational methods for morphology prediction to manage production cost of drugs and improve related pharmaceutical and biopharmaceutical properties. Layer docking approach with molecular dynamics opens a new avenue for crystal habit prediction in presence of solvent. In the present study, attempts were made to correlate predicted and experimental crystal habits of fluconazole considering solvent interactions using layer docking approach. Simulated results from layer docking approach with methanol as solvent gave two dominant facets (0 1 1) and (1 0 1) with a surface area 22.43% and 19.82% respectively, which were in agreement with the experimental results. Experimentally grown modified crystal habit of fluconazole in methanol showed enhanced dissolution rate (phabit change and absence of any polymorphs, hydrates or solvates. Flow and compressibility of fluconazole recrystallized in methanol was significantly improved when compared to plain drug. This study demonstrates a methodical approach using computational tools for prediction and modification of crystal habit, to enhance dissolution of poorly soluble drugs, for future pharmaceutical applications.

  20. Analysis of Fluconazole in Human Urine Sample by High Performance Liquid Chromatography Method

    International Nuclear Information System (INIS)

    Hermawan, D; Ali, N A Md; Ibrahim, W A Wan; Sanagi, M M

    2013-01-01

    A method for determination of fluconazole, antifungal drug in human urine by using reversed-phased high performance liquid chromatography (RP-HPLC) with ultraviolet (UV) detector was developed. Optimization HPLC conditions were carried out by changing the flow rate and composition of mobile phase. The optimum separation conditions at a flow rate 0.85 mL/min with a composition of mobile phase containing methanol:water (70:30, v/v) with UV detection at a wavelength 254 nm was able to analyze fluconazole within 3 min. The excellent linearity was obtained in the range of concentration 1 to 10 μg/mL with r 2 = 0.998. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.39 μg/mL and 1.28 μg/mL, respectively. Solid phase extraction (SPE) method using octadecylsilane (C18) as a sorbent was used to clean-up and pre-concentrated of the urine sample prior to HPLC analysis. The average recoveries of fluconazole in spiked urine sample was 72.4% with RSD of 3.21% (n=3).

  1. Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

    Directory of Open Access Journals (Sweden)

    Shuyuan Liu

    Full Text Available Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers, amlodipine (AML, nifedipine (NIF, benidipine (BEN and flunarizine (FNZ with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1 expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI <0.5, but no interaction against sensitive strains (FICI = 0.56 ~ 2. The mechanism studies revealed that fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin and YVC1 (encoding calcium channel protein in vacuole membrane.

  2. Cellular characterisation of Candida tropicalis presenting fluconazole-related trailing growth

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    Marcos Dornelas-Ribeiro

    2012-02-01

    Full Text Available We assessed fluconazole susceptibility in 52 Candida tropicalis clinical strains using seven antifungal susceptibility methods, including broth microdilution (BMD [standard M27 A3 (with neutral and acid pH, ATB Fungus 3, Vitek 2 system and flow cytometric analysis] and agar-based methods (disk diffusion and E-test. Trailing growth, detection of cell-associated secreted aspartic proteases (Saps and morphological and ultrastructural traits of these clinical strains were also examined. The ranges of fluconazole 24 h-minimum inhibitory concentration (MIC values were similar among all methods. The essential agreement among the methods used for MIC determinations was excellent and all methods categorised all strains as susceptible, except for one strain that showed a minor error. The presence of the trailing effect was assessed by six methods. Trailing positivity was observed for 86.5-100% of the strains. The exception was the BMD-Ac method where trailing growth was not observed. Morphological and ultrastructural alterations were detected in C. tropicalis trailing cells, including mitochondrial swelling and cell walls with irregular shapes. We tested the production of Saps in 13 C. tropicalis strains expressing trailing growth through flow cytometry. Our results showed that all of the C. tropicalis strains up-regulated surface Sap expression after 24 h or 48 h of exposure to fluconazole, which was not observed in untreated yeast strains. We concluded that C. tropicalis strains expressing trailing growth presented some particular features on both biological and ultrastructural levels.

  3. Release of Fluconazole from Contact Lenses Using a Novel In Vitro Eye Model.

    Science.gov (United States)

    Phan, Chau-Minh; Bajgrowicz, Magdalena; Gao, Huayi; Subbaraman, Lakshman N; Jones, Lyndon W

    2016-04-01

    Rapid drug release followed by a plateau phase is a common observation with drug delivery from contact lenses (CLs) when evaluated in a vial. The aim of this study was to compare the release of fluconazole from seven commercially available daily disposable CLs using a conventional vial-based method with a novel in vitro eye model. An eye model was created using two 3-dimensional printed molds, which were filled with polydimethylsiloxane to obtain an inexpensive model that would mimic the eyeball and eyelid. The model was integrated with a microfluidic syringe pump, and the flow-through was collected in a 12-well microliter plate. Four commercial daily disposable conventional hydrogels (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three silicone hydrogels (somofilcon A, narafilcon A, delefilcon A) were evaluated. These CLs were incubated with fluconazole for 24 h. The drug release was measured in a vial containing 4.8 mL of phosphate-buffered saline and in the polydimethylsiloxane eye model with a 4.8-mL tear flow across 24 h. Overall, conventional hydrogel CLs had a higher uptake and release of fluconazole than silicone hydrogel CLs (p eye model (p eye model under low tear volume was sustained and did not reach a plateau across 24 h (p eyes with fungal keratitis may have increased tearing, which would significantly accelerate drug release.

  4. Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

    Science.gov (United States)

    Liu, Shuyuan; Yue, Longtao; Gu, Wenrui; Li, Xiuyun; Zhang, Liuping; Sun, Shujuan

    2016-01-01

    Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers), amlodipine (AML), nifedipine (NIF), benidipine (BEN) and flunarizine (FNZ) with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1) expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI) <0.5, but no interaction against sensitive strains (FICI = 0.56 ~ 2). The mechanism studies revealed that fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin) and YVC1 (encoding calcium channel protein in vacuole membrane).

  5. Association of systolic blood pressure drop with intravenous administration of itraconazole in children with hemato-oncologic disease

    Directory of Open Access Journals (Sweden)

    Lee HJ

    2015-12-01

    Full Text Available Hyeong Jin Lee,1,* Bongjin Lee,2,* June Dong Park,2 Hyung Joo Jeong,2 Yu Hyeon Choi,2 Hee Young Ju,1 Che Ry Hong,1 Ji Won Lee,1 Hyery Kim,1 Dong In Suh,3 Kyung Duk Park,1 Hyoung Jin Kang,1 Hee Young Shin,1 Hyo Seop Ahn1 1Department of Pediatrics, Cancer Research Institute, 2Division of Pediatric Intensive Care, Department of Pediatrics, 3Division of Pulmonology, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea *These authors contributed equally to this work Purpose: Although few adverse effects have been reported for itraconazole, a widely used antifungal therapy for febrile neutropenia, we found intravenous (IV itraconazole to be associated with serious cases of blood pressure (BP drop. We therefore evaluated the incidence and risk factors for BP drop during IV administration of the drug.Materials and methods: We reviewed the medical records of children with hemato-oncologic disease who were treated with IV itraconazole from January 2012 to December 2013. By analyzing systolic BP (SBP measurements made from 4 hours before through to 4 hours after itraconazole administration, we evaluated the changes in SBP and the risk factors for an SBP drop, especially clinically meaningful (≥20% drops.Results: Itraconazole was administered 2,627 times to 180 patients. The SBP during the 4 hours following itraconazole administration was lower than during the 4 hours before administration (104 [53.0–160.33 mmHg] versus 105 [59.8–148.3 mmHg]; P<0.001. The decrease in SBP was associated with the application of continuous renal replacement therapy (CRRT (P=0.012 and the use of inotropic (P=0.005 and hypotensive drugs (P=0.021. A clinically meaningful SBP drop was seen in 5.37% (141 out of 2,627 of the administrations, and the use of inotropics (odds ratio [OR] 6.70, 95% confidence interval [CI] 3.22–13.92; P<0.001, reducing the dose of inotropics (OR 8.08; 95% CI 1.39–46.94; P=0

  6. Comparison of microbiological assay and HPLC-UV for determination of fluconazole in capsules

    Directory of Open Access Journals (Sweden)

    Kelly Marques Queiroz

    2009-12-01

    Full Text Available The development of a specific agar diffusion bioassay for the quantitative determination of fluconazole formulated in capsules was carried out using a strain of Candida albicans ATCC 18804 as the test organism. A prospective validation of the method showed adequate linearity (r²=0.9995, precision (R.S.D. = 4.0% for intra-day and 4.5% for inter-day precision and accuracy (mean recovery = 102.9%. High performance liquid chromatography was chosen as a comparison method for the fluconazole determination. The contents of fluconazole determined by both methods, for four capsule samples, showed a strong correlation, confirmed by Pearson's correlation coefficient value (r = 0.9884. The bioassay is a suitable method for both research and pharmaceutical industry laboratories.Este trabalho visou ao desenvolvimento e validação de um método microbiológico por difusão em ágar para quantificação de fluconazol em cápsulas utilizando o isolado Candida albicans ATCC 18804 como reagente biológico. O método foi validado e foi verificada linearidade (r²=0,9995, precisão (D.P.R. = 4.0% para precisão intra-dia e 4,5% para precisão inter-dia e exatidão (recuperação média = 102,9%. Concomitantemente, foi realizado o doseamento de fluconazol nas cápsulas por meio de cromatografia líquida de alta eficiência. Os teores encontrados por ambos os métodos demonstraram alta correlação, confirmada pelo Coeficiente de Correlação de Pearson (r = 0,9884. O ensaio microbiológico desenvolvido pode ser considerado ferramenta valiosa tanto para a pesquisa científica quanto para a rotina da indústria farmacêutica.

  7. Determination of minimum inhibitory concentrations of itraconazole, terbinafine and ketoconazole against dermatophyte species by broth microdilution method

    Directory of Open Access Journals (Sweden)

    V K Bhatia

    2015-01-01

    Full Text Available Purpose: Various antifungal agents both topical and systemic have been introduced into clinical practice for effectively treating dermatophytic conditions. Dermatophytosis is the infection of keratinised tissues caused by fungal species of genera Trichophyton, Epidermophyton and Microsporum, commonly known as dermatophytes affecting 20–25% of the world's population. The present study aims at determining the susceptibility patterns of dermatophyte species recovered from superficial mycoses of human patients in Himachal Pradesh to antifungal agents; itraconazole, terbinafine and ketoconazole. The study also aims at determining the minimum inhibitory concentrations (MICs of these agents following the recommended protocol of Clinical and Laboratory Standards Institute (CLSI (M38-A2. Methodology: A total of 53 isolates of dermatophytes (T. mentagrophyte-34 in no., T. rubrum-18 and M. gypseum-1 recovered from the superficial mycoses were examined. Broth microdilution method M38-A2 approved protocol of CLSI (2008 for filamentous fungi was followed for determining the susceptibility of dermatophyte species. Results: T. mentagrophyte isolates were found more susceptible to both itraconazole and ketoconazole as compared to terbinafine (MIC50: 0.125 µg/ml for itraconazole, 0.0625 µg/ml for ketoconazole and 0.5 µg/ml for terbinafine. Three isolates of T. mentagrophytes (VBS-5, VBSo-3 and VBSo-73 and one isolate of T. rubrum (VBPo-9 had higher MIC values of itraconazole (1 µg/ml. Similarly, the higher MIC values of ketoconazole were observed in case of only three isolates of T. mentagrophyte (VBSo-30 = 2 µg/ml; VBSo-44, VBM-2 = 1 µg/ml. The comparative analysis of the three antifungal drugs based on t-test revealed that 'itraconazole and terbinafine' and 'terbinafine and ketoconazole' were found independent based on the P < 0.005 in case of T. mentagrophyte isolates. In case of T. rubrum, the similarity existed between MIC values of 'itraconazole and

  8. Effect of medium composition on static and cidal activity of amphotericin B, itraconazole, voriconazole, posaconazole and terbinafine against Aspergillus fumigatus: a multicenter study.

    NARCIS (Netherlands)

    Tortorano, A.M.; Danaoui, E.; Meletiadis, J.; Mallie, M.; Viviani, M.A.; Piens, M.A.; Rigoni, A.L.; Bastide, J.M.; Grillot, R.

    2002-01-01

    The effect of the medium composition on the fungistatic (MIC) and fungicidal (MLC) activity of amphotericin B, itraconazole, voriconazole, posaconazole and terbinafine against four Aspergillus fumigatus strains has been investigated by four European laboratories. MICs were determined by broth

  9. Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence

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    Ronen Ben-Ami

    2016-08-01

    Full Text Available Candida glabrata causes persistent infections in patients treated with fluconazole and often acquires resistance following exposure to the drug. Here we found that clinical strains of C. glabrata exhibit cell-to-cell variation in drug response (heteroresistance. We used population analysis profiling (PAP to assess fluconazole heteroresistance (FLCHR and to ask if it is a binary trait or a continuous phenotype. Thirty (57.6% of 52 fluconazole-sensitive clinical C. glabrata isolates met accepted dichotomous criteria for FLCHR. However, quantitative grading of FLCHR by using the area under the PAP curve (AUC revealed a continuous distribution across a wide range of values, suggesting that all isolates exhibit some degree of heteroresistance. The AUC correlated with rhodamine 6G efflux and was associated with upregulation of the CDR1 and PDH1 genes, encoding ATP-binding cassette (ABC transmembrane transporters, implying that HetR populations exhibit higher levels of drug efflux. Highly FLCHRC. glabrata was recovered more frequently than nonheteroresistant C. glabrata from hematogenously infected immunocompetent mice following treatment with high-dose fluconazole (45.8% versus 15%, P = 0.029. Phylogenetic analysis revealed some phenotypic clustering but also variations in FLCHR within clonal groups, suggesting both genetic and epigenetic determinants of heteroresistance. Collectively, these results establish heteroresistance to fluconazole as a graded phenotype associated with ABC transporter upregulation and fluconazole efflux. Heteroresistance may explain the propensity of C. glabrata for persistent infection and the emergence of breakthrough resistance to fluconazole.

  10. The trend of susceptibilities to amphotericin B and fluconazole of Candida species from 1999 to 2002 in Taiwan

    Directory of Open Access Journals (Sweden)

    Cheng Hsiao-Hsu

    2005-11-01

    Full Text Available Abstract Background Candida species have various degrees of susceptibility to common antifungal drugs. The extent of resistance to amphotericin B and fluconazole of Candida glabrata isolates causing candidemia has been reported. Active surveillance may help us to monitor the trend of susceptibility to antifungal drugs and to determine if there is an emerging co-resistance to both drugs of Candida species, specifically, of C. glabrata in Taiwan. Methods The susceptibilities to amphotericin B and fluconazole of Candida species collected in 1999 and 2002 of the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY were determined by the microdilution method. Results The antifungal susceptibilities of 342 and 456 isolates collected from 11 hospitals participating in both TSARY 1999 and TSARY 2002, respectively, have been determined. The resistance rate to amphotericin B has increased from 0.3% in the TSARY1999 to 2.2% in the TSARY 2002. In contrast, the resistance rate to fluconazole has decreased from 8.8% to 2.2%. Nevertheless, significantly more C. glabrata isolates were not susceptible to fluconazole in the TSARY 2002 (47.4% than that in the TSARY 1999 (20.8%. There were 9.8% and 11% of C. glabrata isolates having susceptible-dose dependent and resistant phenotype to fluconazole in the TSARY 1999, verse 45.3% and 2.1% in the TSARY 2002. Conclusion There was an increase of resistance rate to amphotericin B in C. glabrata. On the other hand, although the resistance rate to fluconazole has decreased, almost half of C. glabrata isolates were not susceptible to this drug. Hence, continuous monitoring the emerging of co-resistance to both amphotericin B and fluconazole of Candida species, specifically, of C. glabrata, will be an important early-warning system.

  11. Use of Drawing Lithography-Fabricated Polyglycolic Acid Microneedles for Transdermal Delivery of Itraconazole to a Human Basal Cell Carcinoma Model Regenerated on Mice

    Science.gov (United States)

    Zhang, Jennifer; Wang, Yan; Jin, Jane Y.; Degan, Simone; Hall, Russell P.; Boehm, Ryan D.; Jaipan, Panupong; Narayan, Roger J.

    2016-04-01

    Itraconazole is a triazole agent that is routinely used for treatment of nail infections and other fungal infections. Recent studies indicate that itraconazole can also inhibit the growth of basal cell carcinoma (BCC) through suppression of the Sonic Hedgehog (SHH) signaling pathway. In this study, polyglycolic acid microneedle arrays and stainless steel microneedle arrays were used for transdermal delivery of itraconazole to a human BCC model which was regenerated on mice. One-by-four arrays of 642- μm-long polyglycolic acid microneedles with sharp tips were prepared using injection molding and drawing lithography. Arrays of 85 stainless steel 800- μm-tall microneedles attached to syringes were obtained for comparison purposes. Skin grafts containing devitalized split-thickness human dermis that had been seeded with human keratinocytes transduced to express human SHH protein were sutured to the skin of immunodeficient mice. Mice with this human BCC model were treated daily for 2 weeks with itraconazole dissolved in 60% dimethylsulfoxane and 40% polyethylene glycol-400 solution; transdermal administration of the itraconazole solution was facilitated by either four 1 × 4 polyglycolic acid microneedle arrays or stainless steel microneedle arrays. The epidermal tissues treated with polyglycolic acid microneedles or stainless steel microneedles were markedly thinner than that of the control (untreated) graft tissue. These preliminary results indicate that microneedles may be used to facilitate transdermal delivery of itraconazole for localized treatment of BCC.

  12. The in vitro and in vivo efficacy of fluconazole in combination with farnesol against Candida albicans isolates using a murine vulvovaginitis model.

    Science.gov (United States)

    Bozó, Aliz; Domán, Marianna; Majoros, László; Kardos, Gábor; Varga, István; Kovács, Renátó

    2016-11-01

    Farnesol is a quorum-sensing molecule that inhibits biofilm formation in Candida albicans. Previous in vitro data suggest that, in combination with certain antifungals, farnesol may have an adjuvant anti-biofilm agent. However, the in vivo efficacy of farnesol is very questionable. Therefore, the in vitro and in vivo activity of fluconazole combined with farnesol was evaluated against C. albicans biofilms using fractional inhibitory concentration index (FICI) determination, time-kill experiments and a murine vulvovaginitis model. The median biofilm MICs of fluconazole-sensitive C. albicans isolates ranged between 4 -> 512 mg/L and 150-300 μM for fluconazole and farnesol, respectively. These values were 512 -> 512 mg/L and > 300 μM for fluconazole-resistant clinical isolates. Farnesol decreased the median MICs of fluconazole by 2-64-fold for biofilms. Based on FICI, synergistic interaction was observed only in the case of the sessile SC5314 reference strain (FICIs: 0.16-0.27). In time-kill studies, only the 512 mg/L fluconazole and 512 mg/L fluconazole + 75 μM farnesol reduced biofilm mass significantly at each time point in the case of all isolates. The combination reduced the metabolic activity of biofilms for all isolates in a concentration- and time-dependent manner. Our findings revealed that farnesol alone was not protective in a murine vulvovaginitis model. Farnesol was not beneficial in combination with fluconazole for fluconazole-susceptible isolates, but partially increased fluconazole activity against one fluconazole-resistant isolate, but not the other one.

  13. [Itraconazole and secnidazole capsules vs. vaginal ovules of fluocinolone acetonide, nystatin and metronidazole in the symptomatic treatment of vaginitis].

    Science.gov (United States)

    Alvarado García, A; Gaviño Ambriz, S

    1998-04-01

    Evaluation of oral treatment in vaginitis and vaginosis using Itraconazol and sechidazol, in comparison to topic treatment using vaginal ovules of acetonido of fluocinolona 0.50 mg, nistatina 100,000 U and metronidazol 500 mg. Longitudinal, prospective and open comparative study. Servicio de Reproducción Humana(Human Reproduction Department), Centro Médico Nacional "20 de Noviembre". Forty female patients, without any relevant differences in their general characteristics, chose diagnosis was vaginitis and vaginosis, who were medically treated through external consultation, divided in two groups of twenty each one. Group 1 oral treatment with itraconazol and secnidazol. Group 2 had topic treatment with fluocinolona, nistatina and metronidazol. All of the patients were controlled in seven and fourteen days time, in order to evaluate the intensity of their clinical symptomatology, as well as the efficacy in both ways of treatment. Leukorrhea was the most important symptom in all the cases, going from minor to serious white discharge. After the treatment, we found a relevant difference statistically significative in patients treated with intraconazol and secnidazol. We did not find any differences in relation to ardor, pruritus, dispareunia and disuria at post-treatment evaluation. However, group 1 betterment was statistically significative between the first and the seventh days of treatment. Treating vaginitis or vaginosis (or both) with itraconazol and secnidazol takes less time for betterment in addition to comfort and easiness of oral administration; therefore, we consider them proper medicines in these specific cases.

  14. Clinical features, fungal load, coinfections, histological skin changes, and itraconazole treatment response of cats with sporotrichosis caused by Sporothrix brasiliensis.

    Science.gov (United States)

    de Souza, Elaine Waite; Borba, Cintia de Moraes; Pereira, Sandro Antonio; Gremião, Isabella Dib Ferreira; Langohr, Ingeborg Maria; Oliveira, Manoel Marques Evangelista; de Oliveira, Raquel de Vasconcellos Carvalhaes; da Cunha, Camila Rocha; Zancopé-Oliveira, Rosely Maria; de Miranda, Luisa Helena Monteiro; Menezes, Rodrigo Caldas

    2018-06-13

    Zoonotic sporotrichosis caused by the fungus Sporothrix brasiliensis is usually severe in cats. This study investigated the associations between clinical features, fungal load, coinfections, histological skin changes, and response to itraconazole in cats with sporotrichosis caused by S. brasiliensis. Fifty-two cats with skin lesions and a definitive diagnosis of sporotrichosis were treated with itraconazole for a maximum period of 36 weeks. The animals were submitted to clinical examination and two subsequent collections of samples from the same skin lesion for fungal diagnosis and histopathology, as well as serology for feline immunodeficiency (FIV) and leukaemia (FeLV) viruses. Thirty-seven (71%) cats were clinically cured. Nasal mucosa lesions and respiratory signs were associated with treatment failure. Cats coinfected with FIV/FeLV (n = 12) had a lower neutrophil count in the lesion. A high fungal load in skin lesions was linked to young age and treatment failure, as well as to a longer time of wound healing, poorly formed granulomas and fewer neutrophils, macrophages and lymphocytes in these lesions. These results indicate that itraconazole is effective, but nasal mucosal involvement, respiratory signs and high fungal loads in skin lesions are predictors of treatment failure that will assist in the development of better treatment protocols for cats.

  15. Iatrogenic Cushing syndrome in patients receiving inhaled budesonide and itraconazole or ritonavir: two cases and literature review.

    Science.gov (United States)

    Blondin, Marie-Christine; Beauregard, Hugues; Serri, Omar

    2013-01-01

    To present two cases of iatrogenic Cushing syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with ritonavir and itraconazole. We present the clinical and biochemical data of two patients in whom diagnosis of Cushing syndrome was caused by this interaction. We also reviewed the pertinent literature and management options. A 71-year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient rapidly developed a typical Cushing syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 AM cortisol concentrations were suppressed at 0.76 and 0.83 μg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46-year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of human immunodeficiency virus (HIV). In the following months, she developed typical signs of Cushing syndrome. Her morning serum cortisol concentration was 1.92 μg/dL. A cosyntropin stimulation test showed values of serum cortisol of Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir.

  16. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine

    Science.gov (United States)

    Damkier, Per; Hansen, Lone L; Brøsen, Kim

    1999-01-01

    Aims In vitro studies suggest that the oxidation of quinidine to 3-hydroxyquinidine is a specific marker reaction for CYP3A4 activity. To assess the possible use of this reaction as an in vivo marker of CYP3A4 activity, we studied the involvement of cytochromes CYP2C9, CYP2E1 and CYP3A4 in the in vivo oxidative metabolism of quinidine. Methods An open study of 30 healthy young male volunteers was performed. The pharmacokinetics of a 200 mg single oral dose of quinidine was studied before and during daily administration of 100 mg diclofenac, a CYP2C9 substrate (n=6); 200 mg disulfiram, an inhibitor of CYP2E1 (n=6); 100 mg itraconazole, an inhibitor of CYP3A4 (n=6); 250 ml single strength grapefruit juice twice daily, an inhibitor of CYP3A4 (n=6); 250 mg of erythromycin 4 times daily, an inhibitor of CYP3A4 (n=6). Probes of other enzyme activities, caffeine (CYP1A2), sparteine (CYP2D6), mephenytoin (CYP2C19), tolbutamide (CYP2C9) and cortisol (CYP3A4) were also studied. Results Concomitant administration of diclofenac reduced the partial clearance of quinidine by N-oxidation by 27%, while no effect was found for other pharmacokinetic parameters of quinidine. Concomitant administration of disulfiram did not alter any of the pharmacokinetic parameters of quinidine. Concomitant administration of itraconazole reduced quinidine total clearance, partial clearance by 3-hydroxylation and partial clearance by N-oxidation by 61, 84 and 73%, respectively. The renal clerance was reduced by 60% and the elimination half-life increased by 35%. Concomitant administration of grapefruit juice reduced the total clearance of quinidine and its partial clearance by 3-hydroxylation and N-oxidation by 15, 19 and 27%, respectively. The elimination half-life of quinidine was increased by 19%. The caffeine metabolic index was reduced by 25%. Concomitant administration of erythromycin reduced the total clearance of quinidine and its partial clearance by 3-hydroxylation and N-oxidation by 34, 50

  17. The Effect on mortality of fluconazole or echinocandins treatment in candidemia in internal medicine wards [corrected].

    Directory of Open Access Journals (Sweden)

    Francesco G De Rosa

    Full Text Available The incidence of candidemia has increased over the past two decades, with an increased number of cases in Internal Medicine and a prevalence ranging from 24% to 57%. This single-center retrospective study was performed to evaluate the epidemiology and the risk factors associated with mortality of candidemia in patients admitted to Internal Medicine wards (IMWs of the City of Health and Sciences, Molinette Hospital, Turin, from January 2004 to December 2012. For each patient, demographic, clinical and microbiological data were collected. A case of candidemia was defined as a patient with at least one blood culture positive for Candida spp. Amongst 670 episodes of candidemia, 274 (41% episodes occurred in IMWs. The mortality was 39% and was associated at multivariate analysis with sepsis, cirrhosis and neurologic diseases, whilst removal of central venous catheter ≤48h was significantly associated with survival. In the 77 patients treated with early antifungal therapy the mortality was 29% and was not significantly different with caspofungin or fluconazole, whilst in patients with definitive therapy the mortality was significantly lower with echinocandins compared to fluconazole (11.7% Vs. 39%; p=0.0289, a finding confirmed by multivariate analysis. The mortality was significantly associated with sepsis, cirrhosis and neurologic diseases, whilst CVC removal ≤48h was associated with survival. In patients with early therapy, fluconazole or caspofungin were equally effective. However, echinocandins were significantly more effective as definitive treatment, a finding not explained by differences in treatment delays. Further studies are needed to understand the full potential of these different therapeutic strategies in IMWs.

  18. Determination of minimum inhibitory concentrations of itraconazole, terbinafine and ketoconazole against dermatophyte species by broth microdilution method.

    Science.gov (United States)

    Bhatia, V K; Sharma, P C

    2015-01-01

    Various antifungal agents both topical and systemic have been introduced into clinical practice for effectively treating dermatophytic conditions. Dermatophytosis is the infection of keratinised tissues caused by fungal species of genera Trichophyton, Epidermophyton and Microsporum, commonly known as dermatophytes affecting 20-25% of the world's population. The present study aims at determining the susceptibility patterns of dermatophyte species recovered from superficial mycoses of human patients in Himachal Pradesh to antifungal agents; itraconazole, terbinafine and ketoconazole. The study also aims at determining the minimum inhibitory concentrations (MICs) of these agents following the recommended protocol of Clinical and Laboratory Standards Institute (CLSI) (M38-A2). A total of 53 isolates of dermatophytes (T. mentagrophyte-34 in no., T. rubrum-18 and M. gypseum-1) recovered from the superficial mycoses were examined. Broth microdilution method M38-A2 approved protocol of CLSI (2008) for filamentous fungi was followed for determining the susceptibility of dermatophyte species. T. mentagrophyte isolates were found more susceptible to both itraconazole and ketoconazole as compared to terbinafine (MIC50: 0.125 µg/ml for itraconazole, 0.0625 µg/ml for ketoconazole and 0.5 µg/ml for terbinafine). Three isolates of T. mentagrophytes (VBS-5, VBSo-3 and VBSo-73) and one isolate of T. rubrum (VBPo-9) had higher MIC values of itraconazole (1 µg/ml). Similarly, the higher MIC values of ketoconazole were observed in case of only three isolates of T. mentagrophyte (VBSo-30 = 2 µg/ml; VBSo-44, VBM-2 = 1 µg/ml). The comparative analysis of the three antifungal drugs based on t-test revealed that 'itraconazole and terbinafine' and 'terbinafine and ketoconazole' were found independent based on the P terbinafine and ketoconazole'. The MIC values observed in the present study based on standard protocol M38-A2 of CLSI 2008 might serve as reference for further studies

  19. Características gerais da ação, do tratamento e da resistência fúngica ao fluconazol = General traits of action, treatment and fungal resistance to fluconazol

    OpenAIRE

    Santos Júnior, Inaldo Domingos dos

    2005-01-01

    Objetivos: O objetivo deste trabalho foi destacar o modo e espectro de ação, as características do tratamento e os mecanismos pelos quais os fungos podem apresentar resistência ao fluconazol, de modo a fornecer aos profissionais de saúde um material útil para a prevenção da disseminação desta resistência Método: Foi realizada uma revisão na literatura especializada dos bancos de dados internacionais SCIELO, LILACS e HIGHWIRE Resultados: O fluconazol é um composto bitriazólico sintético,...

  20. Características gerais da ação, do tratamento e da resistência fúngica ao fluconazol = General traits of action, treatment and fungal resistance to fluconazol

    OpenAIRE

    Santos Júnior, Inaldo Domingos dos

    2005-01-01

    Objetivos: O objetivo deste trabalho foi destacar o modo e espectro de ação, as características do tratamento e os mecanismos pelos quais os fungos podem apresentar resistência ao fluconazol, de modo a fornecer aos profissionais de saúde um material útil para a prevenção da disseminação desta resistência. Método: Foi realizada uma revisão na literatura especializada dos bancos de dados internacionais SCIELO, LILACS e HIGHWIRE. Resultados: O fluconazol é um composto bitriazólico sintético, usa...

  1. Fluconazole therapy for treatment of invasive candidiasis in Intensive Care patients. Is it still valid from a pharmacological point of view?

    Directory of Open Access Journals (Sweden)

    Mario Musu

    2014-01-01

    Full Text Available Fluconazole – antimycotic belonging to the first generation azoles – is widely used as treatment for invasive candidiasis and candidemia in numerous clinical settings as Neonatal Intensive Care Unit (NICU and adult Intensive Care Unit (ICU, as well as oncology, onco-hematology and solid organ transplantation. More recently use of antimycotics has spread to medical divisions, where fungal infections represent an emerging problem due to population’s ageing, malnourishment and important comorbidities. Fluconazole is effective against numerous Candida species, particularly against albicans, tropicalis and parapsilosis strains. On the other hand, C. krusei is intrinsically resistant to fluconazole and C. glabrata can be sensitive or resistant in a dose dependent fashion. Epidemiological variability is noteworthy and depends on the geographical location of the institution, the clinical setting, and the frequency and intensity of fluconazole employment for invasive candidiasis. In many ICUs fluconazole sensitive C. albicans is cultured in 50% of positive samples, while the remaining 50% show growth of variably sensitive fungal species, often resistant to fluconazole. Due to increasingly frequent emergence of resistant strains of Candida spp., American guidelines (IDSA in 2009, and European ones (ESCMID in 2012, recommended substitution of fluconazole with echinocandines as first line therapy in patients with severe disease, as defined by an APACHE II score greater than 15. Thus fluconazole must be limited to low risk cases, treatment of sensitive strains and de-escalation from echinocandin therapy, after microbiological diagnosis and drug resistance profile characterization.

  2. Pharmacokinetics of sequential intravenous and enteral fluconazole in critically ill surgical patients with invasive mycoses and compromised gastro-intestinal function

    NARCIS (Netherlands)

    Buijk, S L; Gyssens, I C; Mouton, J W; Verbrugh, H A; Touw, D J; Bruining, H A

    OBJECTIVES: (1) To determine the pharmacokinetics of sequential intravenous and enteral fluconazole in the serum of surgical intensive care unit (ICU) patients with deep mycoses. (2) To determine the concentrations of fluconazole reached at the site of infection. (3) To determine if enteral

  3. Influence of doxorubicin on fluconazole susceptibility and efflux pump gene expression of Candida dubliniensis.

    LENUS (Irish Health Repository)

    Schulz, Bettina

    2012-05-01

    The effect of doxorubicin (DOX) on the fluconazole (FLU) susceptibility of C. dubliniensis was investigated. Isolates were exposed to DOX and FLU in a chequerboard assay and resistance gene expressions were analysed after DOX exposure. The susceptibility of the yeast to FLU was decreased in the presence of DOX in the chequerboard assay with FIC indices suggesting an antagonistic effect. Gene expression analyses showed an overexpression of CdCDR2. Hence, DOX was found to have an impact on resistance mechanisms in C. dubliniensis isolates.

  4. Actividad antifúngica del extracto de etanol Schinus molle y el fluconazol sobre Candida albicans

    OpenAIRE

    Saravia León, Natalia; Guillinta Vallejos, Guido

    2012-01-01

    Objetivo. Determinar la actividad antifúngica del extracto de etanol Schinus molle y fluconazol sobre Candida albicans. Material y métodos. El estudio es experimental y transversal. La planta se recolectó en el departamento de Huancavelica provincia de Junín, se utilizó las hojas para preparar el extracto etanolico de Schinus molle. Los discos de extracto de etanol Schinus molle se obtuvieron en la Facultad de Farmacia y Bioquímica de la Universidad Nacional Mayor de San Marcos. El f...

  5. Fern extracts potentiate fluconazole activity and inhibit morphological changes in Candida species

    Directory of Open Access Journals (Sweden)

    Maria A. Freitas

    2017-11-01

    Conclusions: The extracts obtained from the fern species L. venustum and P. calomelanos dose not present significant antifungal activity. However, P. calomelanos potentiates the activity of fluconazole and both extracts inhibits the morphological changes in Candida species, indicating that they have potential pharmacological activity as modulators of fungal biology. Therefore, novel studies are required to characterize the interference of these extracts in the virulence and pathogenicity of Candida species as well as the potential of fern species to treat fungal infections.

  6. Fluconazole Resistance Patterns in Candida Species that Colonize Women with HIV Infection

    Directory of Open Access Journals (Sweden)

    Lulu Zhang, MD

    2014-12-01

    Conclusions: Systemic antifungal therapy, including a vaginal topical regimen in women with HIV infection correlated with reduced fluconazole susceptibility of oral and vaginal isolates. Genotype profiling has disclosed that a majority of isolates from the same individual are clustered together, suggesting the likelihood of an original strain with some microevolution. We observed a change from a susceptibility dose dependent to a resistant phenotype of isolates in 2 women with HIV infection, even though no treatments were received during the 4-month study and the prior 2 years.

  7. Investigation of itraconazole ternary amorphous solid dispersions based on povidone and Carbopol.

    Science.gov (United States)

    Meng, Fan; Meckel, Jordan; Zhang, Feng

    2017-08-30

    We investigate a ternary system that consists of itraconazole (ITZ) and two polymers: povidone K12 and Carbopol 907. The interactions between these two polymers and their effects on the properties of ternary ITZ amorphous solid dispersions (ASDs) are studied. These two polymers can form a water-insoluble complex in acidic aqueous media. The critical pH is determined to be 4.17. The weight percentage of Carbopol 907 in the interpolymer complex range from 59 to 70%, depending on the initial ratios between these two polymers in the starting solutions. This complexation is driven by a negative enthalpy change from the H-bonding between the two polymers and a positive entropy change from the freed water molecules. Due to the slow precipitation of the interpolymer complex in aqueous media, the attempt to prepare ternary ASD using solvent-controlled coprecipitation is not successful. Melt extrusion is identified to be the only viable method to prepare this ternary ASD. We find that interpolymer complex-based ASDs are physically less stable and demonstrate the poorest drug-release properties when compared to individual polymer-based binary ASDs. This study illustrates that the too strong interaction between polymers in ternary ASDs is detrimental to their performance. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Formulation of itraconazole nanococrystals and evaluation of their bioavailability in dogs.

    Science.gov (United States)

    De Smet, Lieselotte; Saerens, Lien; De Beer, Thomas; Carleer, Robert; Adriaensens, Peter; Van Bocxlaer, Jan; Vervaet, Chris; Remon, Jean Paul

    2014-05-01

    The aim of the study is to increase the bioavailability of itraconazole (ITRA) using nanosized cocrystals prepared via wet milling of ITRA in combination with dicarboxylic acids. Wet milling was used in order to create a nanosuspension of ITRA in combination with dicarboxylic acids. After spray-drying and bead layering, solid state was characterized by MDSC, XRD, Raman and FT-IR. The release profiles and bioavailability of the nanococrystalline suspension, the spray-dried and bead layered formulation were evaluated. A monodisperse nanosuspension (549±51nm) of ITRA was developed using adipic acid and Tween®80. Solid state characterization indicated the formation of nanococrystals by hydrogen bounds between the triazole group of ITRA and the carboxyl group of adipic acid. A bioavailability study was performed in dogs. The faster drug release from the nanocrystal-based formulation was reflected in the in vivo results since Tmax of the formulations was obtained 3h after administration, while Tmax of the reference formulation was observed only 6h after administration. This fast release of ITRA was obtained by a dual concept: manufacturing of nanosized cocrystals of ITRA and adipic acid via wet milling. Formation of stable nanosized cocrystals via this approach seems a good alternative for amorphous systems to increase the solubility and obtain a fast drug release of BCS class II drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Development of Liposome containing sodium deoxycholate to enhance oral bioavailability of itraconazole

    Directory of Open Access Journals (Sweden)

    Zhenbao Li

    2017-03-01

    Full Text Available The aim of this study was to enhance oral bioavailability of itraconazole (ITZ by developing Liposome containing sodium deoxycholate (ITZ-Lip-NaDC. The liposome, consisting of egg yolk lecithin and sodium deoxycholate, was prepared by thin-film dispersion method. Differential Scanning Calorimetry (DSC results indicated an amorphous state in the liposome. The physicochemical characteristics including particle size, morphology, entrapment efficiency, dissolution properties were also investigated. The performance of single-pass intestinal infusion exhibited that the transport order of intestinal segment was jejunum, duodenum, colon and ileum, and that all the segments participated in the absorption of ITZ in intestinal tract. The bioavailability study in rats showed that the AUC0-72 of the liposome was nearly 1.67-fold higher than that of commercial capsules (SPORANOX in terms of oral administration, and the RSD of AUC0-72 of ITZ-Lip-NaDC was also decreased. Our results indicated that ITZ-Lip-NaDC liposome was facilitated to improve dissolution efficiency, augment transmembrane absorption, and then enhance the oral bioavailability of ITZ, successfully.

  10. Association of itraconazole and potassium iodide in the treatment of feline sporotrichosis: a prospective study.

    Science.gov (United States)

    Reis, Érica G; Schubach, Tânia M P; Pereira, Sandro A; Silva, Jéssica N; Carvalho, Beatriz W; Quintana, Marcel S B; Gremião, Isabella D F

    2016-10-01

    Feline sporotrichosis is an endemic disease in Rio de Janeiro, Brazil, where zoonotic transmission of Sporothrix spp. has been reported since 1998. Itraconazole (ITZ) remains the first choice for treating this disease in cats. However, there have been reports of therapeutic failure and a long-term endeavor. Potassium iodide (KI), considered in the past as a drug with variable effectiveness in cats with sporotrichosis, arises as an important option in the treatment of cats from the endemic area of Rio de Janeiro. In order to evaluate the effectiveness of the association of ITZ and KI in naive cats with sporotrichosis, a prospective cohort study was conducted on 30 cats receiving ITZ 100 mg/day and KI 2.5 mg-20 mg/kg/day. Clinical and laboratory adverse effects were assessed once a month according to the standard care protocol. The cure rate was 96.15% within a median of 14 weeks of treatment. Adverse effects were observed in 50% of cats and were managed with a temporary drug suspension and/or a hepatoprotective therapy. The association of ITZ and KI emerges as an effective option for the treatment of feline sporotrichosis. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Development of intranasal nanovehicles of itraconazole and their immunological activities for the therapy of rhinovirus infection.

    Science.gov (United States)

    Lee, Jeong-Jun; Shim, Aeri; Jeong, Jae Young; Lee, Song Yi; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2016-07-01

    Itraconazole (ITZ)-loaded microemulsion (ME) systems for intranasal (IN) delivery were developed for the treatment of human rhinovirus serotype 1B (HRV1B) infection. ITZ was incorporated into the oil-in-water (o/w) ME formulation composed of benzyl alcohol (oil), Cremophor EL (surfactant), Solutol HS15 (cosurfactant), and water. The optimized composition of ME was determined by constructing pseudo-ternary phase diagram. ITZ ME formulation with about 150nm mean diameter and spherical shape was prepared and the solubility of ITZ in blank ME was markedly improved (up to 13.9mg/mL). The initial value of droplet size was maintained with four times dilution in the aqueous buffer and 72h incubation. Released amounts of drug from ME formulation were significantly enhanced compared to drug suspension group (p<0.05). Particularly, ITZ ME group displayed lower levels of inflammatory markers in the lung compared to ITZ suspension group after their IN administration in the HRV1B-infected mouse model (p<0.05). Developed ITZ ME formulation via IN route can be a promising candidate for the treatment of rhinovirus infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Mitochondrial respiratory pathways inhibition in Rhizopus oryzae potentiates activity of posaconazole and itraconazole via apoptosis.

    Directory of Open Access Journals (Sweden)

    Fazal Shirazi

    Full Text Available The incidence of mucormycosis has increased drastically in immunocompromised patients. Also the array of targets whose inhibition results in Mucorales death is limited. Recently, researchers identified mitochondria as important regulators of detoxification and virulence mechanisms in fungi. In this context, targeting the mitochondrial respiratory chain may provide a new platform for antifungal development. We hypothesized that targeting respiratory pathways potentiates triazoles activity via apoptosis. We found that simultaneous administration of antimycin A (AA and benzohydroxamate (BHAM, inhibitors of classical and alternative mitochondrial pathways respectively, resulted in potent activity of posaconazole (PCZ and itraconazole (ICZ against Rhizopus oryzae. We observed cellular changes characteristic of apoptosis in R. oryzae cells treated with PCZ or ICZ in combination with AA and BHAM. The fungicidal activity of this combination against R. oryzae was correlated with intracellular reactive oxygen species accumulation (ROS, phosphatidylserine externalization, mitochondrial membrane depolarization, and increased caspase like activity. DNA fragmentation and condensation assays also revealed apoptosis of R. oryzae cells. These apoptotic features were prevented by the addition of the ROS scavenger N-acetyl-cysteine. Taken together, these findings suggest that the use of PCZ or ICZ in combination with AA and BHAM makes R. oryzae exquisitely sensitive to treatment with triazoles via apoptosis. This strategy may serve as a new model for the development of improved or novel antifungal agents.

  13. Mesophase and size manipulation of itraconazole liquid crystalline nanoparticles produced via quasi nanoemulsion precipitation.

    Science.gov (United States)

    Mugheirbi, Naila A; Tajber, Lidia

    2015-10-01

    The fabrication of drug nanoparticles (NPs) with process-mediated tunable properties and performances continues to grow rapidly during the last decades. This study investigates the synthesis and phase tuning of nanoparticulate itraconazole (ITR) mesophases using quasi nanoemulsion precipitation from acetone/water systems to seek out an alternative pathway to the nucleation-based NP formation. ITR liquid crystalline (LC) phases were formed and nematic-smectic mesomorphism was achieved via controlling solvent:antisolvent temperature difference (ΔTS:AS). The use of ΔTS:AS=49.5°C was associated with a nematic assembly, while intercalated smectic A layering was observed at ΔTS:AS=0°C, with both phases confined in the nanospheres at room temperature. The quasi emulsion system has not been investigated at the nanoscale to date and in contrary to the microscale, quasi nanoemulsion was observed over the solvent:antisolvent viscosity ratios of 1:7-1:1.4. Poly(acrylic acid) in the solvent phase exhibited a concentration dependent interaction when ITR formed NPs. This nanodroplet-based approach enabled the preparation of a stable ITR nanodispersion using Poloxamer 407 at 80°C, which was unachievable before using precipitation via nucleation. Findings of this work lay groundwork in terms of rationalised molecular assembly as a tool in designing pharmaceutical LC NPs with tailored properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Comparison of spray drying, electroblowing and electrospinning for preparation of Eudragit E and itraconazole solid dispersions.

    Science.gov (United States)

    Sóti, Péter Lajos; Bocz, Katalin; Pataki, Hajnalka; Eke, Zsuzsanna; Farkas, Attila; Verreck, Geert; Kiss, Éva; Fekete, Pál; Vigh, Tamás; Wagner, István; Nagy, Zsombor K; Marosi, György

    2015-10-15

    Three solvent based methods: spray drying (SD), electrospinning (ES) and air-assisted electrospinning (electroblowing; EB) were used to prepare solid dispersions of itraconazole and Eudragit E. Samples with the same API/polymer ratios were prepared in order to make the three technologies comparable. The structure and morphology of solid dispersions were identified by scanning electron microscopy and solid phase analytical methods such as, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman chemical mapping. Moreover, the residual organic solvents of the solid products were determined by static headspace-gas chromatography/mass spectroscopy measurements and the wettability of samples was characterized by contact angle measurement. The pharmaceutical performance of the three dispersion type, evaluated by dissolution tests, proved to be very similar. According to XRPD and DSC analyses, made after the production, all the solid dispersions were free of any API crystal clusters but about 10 wt% drug crystallinity was observed after three months of storage in the case of the SD samples in contrast to the samples produced by ES and EB in which the polymer matrix preserved the API in amorphous state. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Monitoring Amphotericin B and Fluconazole Concentrations in the Plasma and Cerebrospinal Fluid of Patients with Cryptococcal Meningitis

    Directory of Open Access Journals (Sweden)

    Sílvia Regina Cavani Jorge Santos

    2012-10-01

    Full Text Available Objectives: To determine whether amphotericin B (AmB and fluconazole cross the blood-brain barrier in a similar manner in patients with HIV-associated cryptococcal meningitis based on the cerebrospinal fluid (CSF/plasma drug ratio through a comparative study. Methods: This prospective, open-label clinical protocol included 21 male and female patients, 28-55 years of age. The patients were infected with HIV (CD4 50-200 cells/mL and cryptococcal meningitis and were receiving AmB (1 mg/kg daily, infusion of four hours; 6-10 weeks and fluconazole (400 mg 12 qh; until CSF was negative for fungal growth. The patients were informed in detail about all procedures to be performed in the hospital, including blood and CSF sample collection, if required. The study protocol was approved by the hospital’s ethical committee. Plasma samples were obtained by centrifugation at 2800 g for 30 min, and CSF samples were collected by the physician to relieve symptoms caused by intracranial hypertension. The drug concentrations of both antifungal agents were determined in the biological samples using HPLC. Results: The mean drug plasma: CSF concentrations were 2.30:0.3 μg/mL and 31.7:19.4 μg/mL for AmB and fluconazole, respectively. The CSF:plasma ratios were 0.20 (AmB and 0.67 (fluconazole. Conclusions: Unlike fluconazole, the conventional AmB formulation did not reach the optimum CSF drug concentration. However, a high-dose regimen of fluconazole contributes to the outcome of HIV inpatients with severe cryptococcal meningitis.

  16. Technetium-99m labelled fluconazole and antimicrobial peptides for imaging of Candida albicans and Aspergillus fumigatus infections

    Energy Technology Data Exchange (ETDEWEB)

    Lupetti, Antonella [Department of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden (Netherlands); Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Univ. di Pisa (Italy); Welling, Mick M. [Department of Radiology, Division of Nuclear Medicine, LUMC, Leiden (Netherlands); Mazzi, Ulderico [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova (Italy); Nibbering, Peter H. [Department of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden (Netherlands); Pauwels, Ernest K.J. [Department of Radiology, Division of Nuclear Medicine, LUMC, Leiden (Netherlands); Department of Radiology, Leiden University Medical Center (LUMC) (Netherlands)

    2002-05-01

    The aim of this study was to investigate whether technetium-99m labelled fluconazole can distinguish fungal from bacterial infections. Fluconazole was labelled with {sup 99m}Tc and radiochemical analysis showed less than 5% impurities. The labelling solution was injected into animals with experimental infections. For comparison, we used two peptides for infection detection, i.e. UBI 29-41 and hLF 1-11, and human IgG, all labelled with {sup 99m}Tc. Mice were infected with Candida albicans or injected with heat-killed C. albicans or lipopolysaccharides to induce sterile inflammation. Also, mice were infected with Staphylococcus aureus or Klebsiella pneumoniae. Next, accumulation of {sup 99m}Tc-fluconazole and {sup 99m}Tc-labelled peptides/IgG at affected sites was determined scintigraphically. {sup 99m}Tc-fluconazole detected C. albicans infections (T/NT ratio=3.6{+-}0.47) without visualising bacterial infections (T/NT ratio=1.3{+-}0.04) or sterile inflammatory processes (heat-killed C. albicans: T/NT ratio=1.3{+-}0.2; lipopolysaccharide: T/NT ratio=1.4{+-}0.1). C. albicans infections were already seen within the first hour after injection of {sup 99m}Tc-fluconazole (T/NT ratio=3.1{+-}0.2). A good correlation (R{sup 2}=0.864; P<0.05) between T/NT ratios for this tracer and the number of viable C. albicans was found. Although {sup 99m}Tc-UBI 29-41 and {sup 99m}Tc-hLF 1-11 were able to distinguish C. albicans infections from sterile inflammatory processes in mice, these {sup 99m}Tc-labelled peptides did not distinguish these fungal infections from bacterial infections. It is concluded that {sup 99m}Tc-fluconazole distinguishes infections with C. albicans from bacterial infections and sterile inflammations. (orig.)

  17. Fusarium onychomycosis: prevalence, clinical presentations, response to itraconazole and terbinafine pulse therapy, and 1-year follow-up in nine cases.

    Science.gov (United States)

    Ranawaka, Ranthilaka R; Nagahawatte, Ajith; Gunasekara, Thusitha Aravinda

    2015-11-01

    Invasive fusariosis is an infection with Fusarium spp. that primarily affects patients with hematologic malignancies and hematopoietic cell transplant recipients. Wounds, digital ulcers, onychomycosis, and paronychia are the typical cutaneous portals of entry. Early management of mycotic nails in immunocompromised and diabetic hosts is crucial to prevent life-threatening disease. We report nine cases of Fusarium onychomycosis (F. dimerum, n = 5; F. oxysporum, n = 3; Fusarium spp., n = 1) in immunocompetent hosts and their response to itraconazole and terbinafine pulse therapy. The patients received either itraconazole 400 mg daily or terbinafine 500 mg daily for 7 d/month; two pulses for fingernails and three pulses for toenails. Of the 68 confirmed cases of onychomycosis, eight (11.7%) were Fusarium spp.; the ninth patient was culture positive but microscopy negative and responded well to itraconazole. Distal subungual onychomycosis was the commonest clinical manifestation (seven of nine), one had proximal subungual onychomycosis, and total onychodystrophy was noted on four patients. Associated paronychia was marked on 66.7% (six of eight) patients. Itraconazole was given to six patients/25 nails and terbinafine to three patients/20 nails. All nine patients completed treatments, but one defaulted at 12 months follow-up. The efficacy parameters were clinical cure (CC) and mycological cure (MC). At month 12 after the start of treatment, the response was itraconazole CC 13 of 25 (52%)/MC four of six (66.6%) and terbinafine CC four of eight (50%)/MC one of two (50%). Recurrence was noted in four of 13 (30.7%) and eight of 13 (61.5%) cured nails in the itraconazole group within 3 and 12 months, respectively. Fusarium onychomycosis was clinically indistinguishable from other onychomycosis. Both itraconazole and terbinafine pulse therapy were only partially effective on Fusarium onychomycosis. Antifungals that are more effective should be sought. © 2015 The

  18. Coadministration of gemfibrozil and itraconazole has only a minor effect on the pharmacokinetics of the CYP2C9 and CYP3A4 substrate nateglinide

    Science.gov (United States)

    Niemi, Mikko; Backman, Janne T; Juntti-Patinen, Laura; Neuvonen, Mikko; Neuvonen, Pertti J

    2005-01-01

    Background and aims Gemfibrozil, and particularly its combination with itraconazole, greatly increases the area under the plasma concentration-time curve [AUC(0, ∞)] and response to the cytochrome P450 (CYP) 2C8 and 3A4 substrate repaglinide. In vitro, gemfibrozil is a more potent inhibitor of CYP2C9 than of CYP2C8. Our aim was to investigate the effects of the gemfibrozil-itraconazole combination on the pharmacokinetics and pharmacodynamics of another meglitinide analogue, nateglinide, which is metabolized by CYP2C9 and CYP3A4. Methods In a randomized crossover study with two phases, nine healthy subjects took 600 mg gemfibrozil and 100 mg itraconazole (first dose 200 mg) twice daily or placebo for 3 days. On day 3, they ingested a single 30-mg dose of nateglinide. Plasma nateglinide and blood glucose concentrations were measured for up to 12 h. Results During the gemfibrozil-itraconazole phase, the AUC(0, ∞) and Cmax of nateglinide were 47% (range 23–74%; P gemfibrozil and itraconazole had no effect on the formation of the M7 metabolite of nateglinide but impaired its elimination. The blood glucose response to nateglinide was not significantly changed by coadministration of gemfibrozil and itraconazole. Conclusions The combination of gemfibrozil and itraconazole has only a limited influence on the pharmacokinetics of nateglinide. This is in marked contrast to the substantial effect of this combination on the pharmacokinetics of repaglinide. The findings suggest that in vivo gemfibrozil, probably due to its metabolites, is a much more potent inhibitor of CYP2C8 than of CYP2C9. PMID:16042675

  19. Mechanistic understanding of the effect of PPIs and acidic carbonated beverages on the oral absorption of itraconazole based on absorption modeling with appropriate in vitro data.

    Science.gov (United States)

    Fotaki, Nikoletta; Klein, Sandra

    2013-11-04

    Proton pump inhibitors (PPIs) are potent gastric acid suppressing agents and are among the most widely sold drugs in the world. However, even though these antisecretory agents are regarded as safe, they can alter the pharmacokinetics of coadministered drugs. Due to the suppression of gastric acid secretion, they can significantly alter the intragastric pH conditions and are thus likely to affect the bioavailability of coadministered drugs requiring an acidic gastric environment for dissolution and subsequent absorption. Among these drugs can be found itraconazole, a poorly soluble triazole-type antifungal compound. Based on observations reported in the literature, gastric pH alterations due to the coadministration of PPIs or acidic beverages can significantly decrease (PPI) or increase (e.g., Coca-Cola) the bioavailability of this compound. In the present work we estimated the fraction of itraconazole that can be absorbed (fabs) from Sporanox capsules or an itraconazole-HBenBCD complex formulation after oral administration with and without coadministration of a PPI or an acidic (carbonated) beverage. For this purpose, the sensitivity of the two formulations toward the impact of various gastric variations (pH, volume, and emptying rate) as they can result from such administration conditions was studied using solubility and dissolution experiments and a physiologically based absorption model. Simulating coadministration of the two formulations with a PPI resulted in a significant (∼ 10-fold) decrease in itraconazole fabs, indicating the pH to be essential for in vivo dissolution and subsequent absorption. The fabs of itraconazole after coadministration of an acidic beverage (Coca-Cola) was far lower than the fabs obtained for itraconazole alone and did not support the observations reported in the literature. These results clearly indicate that in contrast to PPIs, which seem to affect itraconazole bioavailability mainly via intragastric pH changes, coadministered

  20. Development, optimization and evaluation of polymeric electrospun nanofiber: A tool for local delivery of fluconazole for management of vaginal candidiasis.

    Science.gov (United States)

    Sharma, Rahul; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    The present study is designed to explore the localized delivery of fluconazole using mucoadhesive polymeric nanofibers. Drug-loaded polymeric nanofibers were fabricated by the electrospinning method using polyvinyl alcohol (PVA) as the polymeric constituent. The prepared nanofibers were found to be uniform, non-beaded and non-woven, with the diameter of the fibers ranging from 150 to 180 nm. Further drug release studies indicate a sustained release of fluconazole over a period of 6 h. The results of studies on anti-microbial activity indicated that drug-loaded polymeric nanofibers exhibit superior anti-microbial activity against Candida albicans, when compared to the plain drug.

  1. Análise químico-farmacêutica do fluconazol e especialidade farmacêutica cápsula Chemical pharmaceutical analysis of fluconazole and its pharmaceutical speciality capsule

    Directory of Open Access Journals (Sweden)

    Helenilze Coelho

    2004-06-01

    Full Text Available O fluconazol, derivado triazólico, apresenta atividade antifúngica sendo indicado no tratamento de grande variedade de infecções fúngicas. Este trabalho foi desenvolvido com o objetivo de estabelecer parâmetros de controle de qualidade para a matéria-prima de fluconazol e forma farmacêutica cápsula, subsidiando a elaboração da monografia para a Farmacopéia Brasileira. A matéria-prima do fluconazol pode ser caracterizada pelos seguintes testes: aspecto, solubilidade e faixa de fusão. As impurezas do fluconazol podem ser detectadas por ensaio-limite de cloreto, sulfato, ferro, metais pesados, perda por dessecação e cinzas sulfatadas. Entre as provas de identificação pode-se reconhecer o fármaco por reações químicas de grupos funcionais e por técnicas instrumentais. Para determinação quantitativa do fluconazol na matéria-prima, empregou-se a volumetria com ácido perclórico, em meio acético e detecção do ponto final por indicadores e a espectrofotometria na região do ultravioleta, utilizando hidróxido de sódio 0,1 M a 261 nm. Os parâmetros estabelecidos para o controle de qualidade das amostras de cápsulas dos laboratórios analisados foram aspecto, variação do peso, desintegração, teste de dissolução e perfil de dissolução. O método de doseamento do fluconazol, na forma farmacêutica cápsula, por espectrofotometria na região do ultravioleta apresentou linearidade, especificidade, precisão e exatidão dentro dos critérios de aceitação. Os lotes dos laboratórios C, D apresentaram perfis de dissolução similares ao medicamento de referência (laboratório E, demonstrando haver um comportamento homogêneo para estes medicamentos. Os lotes dos laboratórios A e B não apresentaram homogeneidade quanto ao perfil de dissolução, quando comparado com os demais laboratórios.Fluconazole is a triazole derivated drug with an antifungal activity which is used in the treatment of a large variety of fungal

  2. Desenvolvimento e validação de metodologia analítica para determinação de itraconazol em produtos farmacêuticos por CLAE Development and validation of the methodology for evaluation of itraconazole in pharmaceutical products by HPLC

    Directory of Open Access Journals (Sweden)

    Edith Cristina Laignier Cazedey

    2007-08-01

    Full Text Available Itraconazole is a synthetic antifungal drug administered orally with a broad spectrum of activity against mycotic infections. The present work consists of the development and validation of analytical methodology for evaluation of itraconazole in pharmaceutical products by high performance liquid chromatography. The separation was made using the reversed-phase column LC-18, acetonitrile/diethylamine 0.05% v/v, 60:40 v/v, pH 8.0 as mobile phase, methanol as solvent and detection and quantification at 254 nm. The results here obtained show that the analytical methodology is accurate, reproducible, robust and linear over the concentration range 8.0-12.0 µg/mL of itraconazole. The method was applied to pharmaceutical capsules containg itraconazole pellets and showed to be efficient, yielding good results.

  3. Fungal infections in marrow transplant recipients under antifungal prophylaxis with fluconazole

    Directory of Open Access Journals (Sweden)

    Oliveira J.S.R.

    2002-01-01

    Full Text Available Fungal infection is one of the most important causes of morbidity and mortality in bone marrow transplant (BMT recipients. The growing incidence of these infections is related to several factors including prolonged granulocytopenia, use of broad-spectrum antibiotics, conditioning regimens, and use of immunosuppression to avoid graft-versus-host disease (GvHD. In the present series, we report five cases of invasive mold infections documented among 64 BMT recipients undergoing fluconazole antifungal prophylaxis: 1 A strain of Scedosporium prolificans was isolated from a skin lesion that developed on day +72 after BMT in a chronic myeloid leukemic patient. 2 Invasive pulmonary aspergillosis (Aspergillus fumigatus was diagnosed on day +29 in a patient with a long period of hospitalization before being transplanted for severe aplastic anemia. 3 A tumoral lung lesion due to Rhizopus arrhizus (zygomycosis was observed in a transplanted patient who presented severe chronic GvHD. 4 A tumoral lesion due to Aspergillus spp involving the 7th, 8th and 9th right ribs and local soft tissue was diagnosed in a BMT patient on day +110. 5 A patient with a history of Ph1-positive acute lymphocytic leukemia exhibited a cerebral lesion on day +477 after receiving a BMT during an episode of severe chronic GvHD. At that time, blood and spinal fluid cultures yielded Fusarium sp. Opportunistic infections due to fungi other than Candida spp are becoming a major problem among BMT patients receiving systemic antifungal prophylaxis with fluconazole.

  4. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

    Directory of Open Access Journals (Sweden)

    Yu Lu

    2016-05-01

    Full Text Available Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles.

  5. [The in vitro antifungal activities of fluconazole against pathogenic yeasts recently isolated from clinical specimens].

    Science.gov (United States)

    Yamaguchi, H; Igari, J; Kume, H; Abe, M; Oguri, T; Kanno, H; Kawakami, S; Okuzumi, K; Fukayama, M; Ito, A; Kawata, K; Uchida, K

    1997-09-01

    The emergence of Candida albicans resistance to azole antifungal agents have been reported in the U. S. and Europe. We examined the in vitro antifungal activities of fluconazole against clinical isolates collected by seven investigators in three years to examine if a tendency existed toward the development of azole-resistance among fungal isolates in Japan. The following results were obtained: 1. Sensitivities to fluconazole (FLCZ) were determined for yeast-like fungi, including 113 strains isolated in 1993, 149 strains isolated in 1994 and 205 strains isolated in 1995. No significant differences in sensitivities in the three years were detected. 2. Minimum inhibitory concentrations of FLCZ were 0.1-0.78 microgram/ml for C. albicans and 3.13-25 micrograms/ml for C. glabrata. Strains with 25 micrograms/ml of FLCZ's MIC were detected; two strains of C. krusei and one strain each of C. krusei, Trichospron beigelii and Hansenula anomala. No strains with higher than 50 micrograms/ml MIC of FLCZ were detected. 3. In vitro activities of FLCZ were compared between clinical strains isolated between 1993 and 1995 and clinical strains isolated before the marketing of FLCZ (up to December 1987) or clinical yeasts isolated between 1991 and 1992. No significant differences were observed, suggesting that no tendency existed toward azole resistance among fungal strains examined.

  6. [Keratomycosis due to Fusarium oxysporum treated with the combination povidone iodine eye drops and oral fluconazole].

    Science.gov (United States)

    Diongue, K; Sow, A S; Nguer, M; Seck, M C; Ndiaye, M; Badiane, A S; Ndiaye, J M; Ndoye, N W; Diallo, M A; Diop, A; Ndiaye, Y D; Dieye, B; Déme, A; Ndiaye, I M; Ndir, O; Ndiaye, D

    2015-12-01

    In developing countries where systemic antifungal are often unavailable, treatment of filamentous fungi infection as Fusarium is sometimes very difficult to treat. We report the case of a keratomycosis due to Fusarium oxysporum treated by povidone iodine eye drops and oral fluconazole. The diagnosis of abscess in the cornea was retained after ophthalmological examination for a 28-year-old man with no previous ophthalmological disease, addressed to the Ophthalmological clinic at the University Hospital Le Dantec in Dakar for a left painful red eye with decreased visual acuity lasting for 15 days. The patient did not receive any foreign body into the eye. Samples by corneal scraping were made for microbiological analysis and the patient was hospitalized and treated with a reinforced eye drops based treatment (ceftriaxone+gentamicin). The mycological diagnosis revealed the presence of a mold: F. oxysporum, which motivated the replacement of the initial treatment by eye drops containing iodized povidone solution at 1% because of the amphotericin B unavailability. Due to the threat of visual loss, oral fluconazole was added to the local treatment with eye drops povidone iodine. The outcome was favorable with a healing abscess and visual acuity amounted to 1/200th. Furthermore, we noted sequels such as pannus and pillowcase. The vulgarization of efficient topical antifungal in developing countries would be necessary to optimize fungal infection treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. MALDI-TOF typing highlights geographical and fluconazole resistance clusters in Candida glabrata.

    Science.gov (United States)

    Dhieb, C; Normand, A C; Al-Yasiri, M; Chaker, E; El Euch, D; Vranckx, K; Hendrickx, M; Sadfi, N; Piarroux, R; Ranque, S

    2015-06-01

    Utilizing matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectra for Candida glabrata typing would be a cost-effective and easy-to-use alternative to classical DNA-based typing methods. This study aimed to use MALDI-TOF for the typing of C. glabrata clinical isolates from various geographical origins and test its capacity to differentiate between fluconazole-sensitive and -resistant strains.Both microsatellite length polymorphism (MLP) and MALDI-TOF mass spectra of 58 C. glabrata isolates originating from Marseilles (France) and Tunis (Tunisia) as well as collection strains from diverse geographic origins were analyzed. The same analysis was conducted on a subset of C. glabrata isolates that were either susceptible (MIC ≤ 8 mg/l) or resistant (MIC ≥ 64 mg/l) to fluconazole.According to the seminal results, both MALDI-TOF and MLP classifications could highlight C. glabrata population structures associated with either geographical dispersal barriers (p typing to investigate C. glabrata infection outbreaks and predict the antifungal susceptibility profile of clinical laboratory isolates. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Study of Relationship between Genetic Pattern and Susceptibility to Fluconazole in Clinical Isolated of Trichophyton rubrum

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    F Hadadi

    2015-06-01

    Full Text Available Background & objectives: Trichophyton rubrum is one of the most common pathogenic causes of dermatophytosis. One of the drugs prescribed for fungal infections is fluconazole which belongs to Azoles group of antifungal agents. Recently molecular typing methods have been developed for answering the epidemiological questions and disease recurrence problems. Current study has been conducted on 22 isolates of Trichophyton rubrum obtained from patients randomly. Our aim was the investigation of correlation between genetic pattern and sensitivity to Fluconazole in clinical isolates of Trichophyton rubrum .   Methods: Firstly the genus and species of isolated fungi from patients have been confirmed by macroscopic and microscopic methods. Then, the resistance and sensitivity of isolates against drug have been determined using culture medium containing defined amount of drug. In next step fungal DNA has been extracted by RAPD-PCR (random amplified polymorphic DNA with random sequences of 3 primers.   Results: Each primer produced different amplified pattern, and differences have been observed in genetic pattern of resistant and sensitive samples using each 3 primers, but there was no bond with 100% specificity.   Conclusion: The 12 sensitive isolates which didn’t grow in 50µg/ml concentration of drug, also had limited growth at the lower concentration of drug. Ten resistant isolates which grew in 50µg/ml of drug, also showed resistant to lower concentration of drug. There are differences in genetic pattern of resistant and sensitive samples. RAPD analysis for molecular typing of Trichophyton rubrum seems to be completely suitable.

  9. Bioadhesive tablets containing cyclodextrin complex of itraconazole for the treatment of vaginal candidiasis.

    Science.gov (United States)

    Cevher, Erdal; Açma, Ayşe; Sinani, Genada; Aksu, Buket; Zloh, Mire; Mülazımoğlu, Lütfiye

    2014-08-01

    Itraconazole (ITR) is commonly used in the treatment of Candida infections. It has a nephrotoxic effect and low bioavailability in patients who suffer from renal insufficiency, and its poor solubility in water makes ITR largely unavailable. Cyclodextrins (CyDs) are used to form inclusion complexes with drugs to improve their aqueous solubility and to reduce their side effects. In this study, ITR was complexed with γ-cyclodextrin (γ-CyD), hydroxypropyl-β-cyclodextrin (HP-β-CyD), methyl-β-cyclodextrin (Met-β-CyD) and sulphobutyl ether-β-cyclodextrin (SBE7-β-CyD) to increase its water solubility and to reduce the side effects of the drug without decreasing antifungal activity. Complex formation between ITR and CyDs was evaluated using SEM, (1)H NMR and XRD studies. The antifungal activity of the complexes was analyzed on Candida albicans strains, and the susceptibility of the strains was found to be higher for the ITR-SBE7-β-CyD complex than for the complexes that were prepared with other CyDs. Vaginal bioadhesive sustained release tablet formulations were developed using the ITR-SBE7-β-CyD inclusion complex to increase the residence time of ITR in the vagina, thereby boosting the efficacy of the treatment. The swelling, matrix erosion and bioadhesion properties of formulations and the drug release rate of these tablets were analyzed, and the most therapeutically effective vaginal formulation was determined. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Polymer⁻Surfactant System Based Amorphous Solid Dispersion: Precipitation Inhibition and Bioavailability Enhancement of Itraconazole.

    Science.gov (United States)

    Feng, Disang; Peng, Tingting; Huang, Zhengwei; Singh, Vikramjeet; Shi, Yin; Wen, Ting; Lu, Ming; Quan, Guilan; Pan, Xin; Wu, Chuanbin

    2018-04-24

    The rapid release of poorly water-soluble drugs from amorphous solid dispersion (ASD) is often associated with the generation of supersaturated solution, which provides a strong driving force for precipitation and results in reduced absorption. Precipitation inhibitors, such as polymers and surfactants, are usually used to stabilize the supersaturated solution by blocking the way of kinetic or thermodynamic crystal growth. To evaluate the combined effect of polymers and surfactants on maintaining the supersaturated state of itraconazole (ITZ), various surfactants were integrated with enteric polymer hydroxypropyl methylcellulose acetate succinate (HPMC AS) to develop polymer⁻surfactant based solid dispersion. The supersaturation stability was investigated by in vitro supersaturation dissolution test and nucleation induction time measurement. Compared to the ASD prepared with HPMC AS alone, the addition of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) exhibited a synergistic effect on precipitation inhibition. The results indicated that the TPGS not only significantly reduced the degree of supersaturation which is the driving force for precipitation, but also provided steric hindrance to delay crystal growth by absorbing onto the surface of small particles. Subsequently, the formulations were evaluated in vivo in beagle dogs. Compared with commercial product Sporanox ® , the formulation prepared with HPMC AS/TPGS exhibited a 1.8-fold increase in the AUC (0⁻24 h) of ITZ and a 1.43-fold increase of hydroxyitraconazole (OH-ITZ) in the plasma. Similarly, the extent of absorption was increased by more than 40% when compared to the formulation prepared with HPMC AS alone. The results of this study demonstrated that the ASD based on polymer⁻surfactant system could obviously inhibit drug precipitation in vitro and in vivo, which provides a new access for the development of ASD for poorly water-soluble drug.

  11. Formulation and delivery of itraconazole to the brain using a nanolipid carrier system

    Directory of Open Access Journals (Sweden)

    Lim WM

    2014-05-01

    Full Text Available Wei Meng Lim,1 Paruvathanahalli Siddalingam Rajinikanth,2 Chitneni Mallikarjun,1 Yew Beng Kang11School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia; 2School of Pharmacy, Taylor’s University, Selangor, MalaysiaAbstract: The objectives of this study were to develop and characterize itraconazole (ITZ-loaded nanostructured lipid carriers (NLCs and to study their potential for drug delivery into the brain. Precirol® ATO 5 and Transcutol® HP were selected as the lipid phase, and Tween® 80 and Solutol® HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, –18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery.Keywords: lipid nanoparticles, brain delivery, nanostructured lipid carrier

  12. Formulation and delivery of itraconazole to the brain using a nanolipid carrier system.

    Science.gov (United States)

    Lim, Wei Meng; Rajinikanth, Paruvathanahalli Siddalingam; Mallikarjun, Chitneni; Kang, Yew Beng

    2014-01-01

    The objectives of this study were to develop and characterize itraconazole (ITZ)-loaded nanostructured lipid carriers (NLCs) and to study their potential for drug delivery into the brain. Precirol(®) ATO 5 and Transcutol(®) HP were selected as the lipid phase, and Tween(®) 80 and Solutol(®) HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, -18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery.

  13. Fracture toughness of heat cured denture base acrylic resin modified with Chlorhexidine and Fluconazole as bioactive compounds.

    Science.gov (United States)

    Al-Haddad, Alaa; Vahid Roudsari, Reza; Satterthwaite, Julian D

    2014-02-01

    This study investigated the impact of incorporating Chlorhexidine and Fluconazole as bioactive compounds on the fracture toughness of conventional heat cured denture base acrylic resin material (PMMA). 30 single edge-notched (SEN) samples were prepared and divided into three groups. 10% (mass) Chlorhexidine and 10% (mass) Diflucan powder (4.5% mass Fluconazole) were added to heat cured PMMA respectively to create the two study groups. A third group of conventional heat cured PMMA was prepared as the control group. Fracture toughness (3-point bending test) was carried out for each sample and critical force (Fc) and critical stress intensity factor (KIC) values measured. Data were subject to parametric statistical analysis using one-way ANOVA and Post hoc Bonferroni test (p=0.05). Fluconazole had no significant effect on the fracture toughness of the PMMA while Chlorhexidine significantly reduced the KIC and therefore affected the fracture toughness. When considering addition of a bioactive material to PMMA acrylic, Chlorhexidine will result in reduced fracture toughness of the acrylic base while Fluconazole has no effect. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Invitro Anti-mycotic Activity of Hydro Alcoholic Extracts of Some Indian Medicinal Plants against Fluconazole Resistant Candida albicans.

    Science.gov (United States)

    Varadarajan, Saranya; Narasimhan, Malathi; Malaisamy, Malaiyandi; Duraipandian, Chamundeeswari

    2015-08-01

    Candidiasis is one of the most common opportunistic infections caused by Candida albicans. Fluconazole is the drug of choice for prevention and management of this condition. However, the emergence of fluconazole resistant candidal strains has become a major concern. Many herbs like fenugreek, cinnamon, papaya, oregano, garlic are rich in phytochemical constituents known to express antimycotic activity. With the available information, the present research study was carried out to assess the invitro anti-mycotic activity of hydro alcoholic extracts of Trigonella foenum-graecum seeds, Cinnamomum verum bark and Carica papaya leaves and seeds against fluconazole resistant Candida albicans. Hydro alcoholic extracts of Trigonella foenum-graecum (seeds), Cinnamomum verum (bark), Carica papaya CO.2 strain (male and female leaves) and Carica papaya CO.2 strain (seeds) were prepared by maceration. The anti-mycotic activity of the prepared extracts against Candida albicans was assessed by agar well diffusion method. Three independent experiments were performed in triplicates and the mean and standard deviation were calculated. Minimum inhibitory concentration was determined. The results of the present study revealed that all the extracts exhibited anti-mycotic activity in a dose dependent manner and minimum inhibitory concentration of all the extracts was found to be 15.62 μg/ml. The results of the present study shed light on the fact that plant extracts could be used not only as an alternate drug for management of fluconazole resistant candidiasis but also explored further for oral cancer prevention as a therapeutic adjunct.

  15. Prognostic factors for the clinical effectiveness of fluconazole in the treatment of oral candidiasis in HIV-1-infected individuals

    NARCIS (Netherlands)

    Koks, C. H. W.; Crommentuyn, K. M. L.; Mathôt, R. A. A.; Mulder, J. W.; Meenhorst, P. L.; Beijnen, J. H.

    2002-01-01

    To identify prognostic factors for the clinical effectiveness of fluconazole in HIV-1-infected patients with oropharyngeal candidiasis. The study was designed as a prospective, open label, non-comparative, dose escalating, single centre trial. Thirty-four HIV-1-infected patients with oropharyngeal

  16. In vitro antifungal sensitivity of fluconazole, clotrimazole and nystatin against vaginal candidiasis in females of childbearing age.

    Science.gov (United States)

    Khan, Fouzia; Baqai, Rakhshanda

    2010-01-01

    Vaginal candidiasis is the most common infection of females. A large variety of antifungal drugs are used for treatment. The objective of this study was isolation and identification of Candida from high vaginal swabs and in vitro antifungal activity of Clotrimazole, Fluconazole and Nystatin against Candida. Two hundred and fifty high vaginal swabs were collected from females reporting at different hospitals of Karachi. Wet mount was performed to observe the budding cells of Candida. Vaginal swabs were cultured on Sabouraud's dextrose agar with added antibiotics. Plates were incubated at room temperature for seven days. Chlamydospores of Candida albicans were identified on corn meal agar. Species of Candida were identified on Biggy agar. In vitro antifungal activity of Clotrimazole, Fluconazole and Nystatin was performed by MIC (Minimum inhibitory concentration), well diffusion method and disc diffusion method. Out of 250 high vaginal swabs, Candida species were isolated in 100 (40%) of cases. Out of 100, C. albican 30 (30%), C. tropicalis 21 (21%), C. parapsillosis 10 (10%), C. parakrusi 8 (8%), C. glabrata 8 (8%), C. krusei 3 (3%) were isolated. In vitro antifungal activity indicated Clotrimazole (MIC 16 and 8 microg/ml) effective against 68 (70%) of Candida SPP, Fluconazole (MIC 64 and 32 microg/ml) effective against 29 (36.2%) and Nystatin disc (100 units) was 51 (63.5%) effective. C. albicans was mainly isolated. Clotrimazole was more effective as compared to Fluconazole and Nystatin. Antifungal susceptibility testing should be determined before therapy to avoid treatment failures.

  17. Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

    NARCIS (Netherlands)

    J.P. Jansen (Jeroen); A.K. O'Sullivan (Amy); P.J. Lugtenburg (Pieternella); L.F.R. Span (Lambert); J.J.W.M. Janssen (Jeroen); W.B. Stam (Wiro)

    2010-01-01

    textabstractThe objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind

  18. Effects of fluconazole on the secretome, the wall proteome, and wall integrity of the clinical fungus Candida albicans

    NARCIS (Netherlands)

    Sorgo, A.G.; Heilmann, C.J.; Dekker, H.L.; Bekker, M.; Brul, S.; de Koster, C.G.; de Koning, L.J.; Klis, F.M.

    2011-01-01

    Fluconazole is a commonly used antifungal drug that inhibits Erg11, a protein responsible for 14α-demethylation during ergosterol synthesis. Consequently, ergosterol is depleted from cellular membranes and replaced by toxic 14α-methylated sterols, which causes increased membrane fluidity and drug

  19. Fluconazole Injection

    Science.gov (United States)

    ... an irregular heartbeat; a low level of calcium, sodium, magnesium, or potassium in your blood; or heart, kidney, or liver disease.tell your doctor if you are pregnant, especially if you are in the first 3 months of your pregnancy, plan to become pregnant, or are breast-feeding. ...

  20. Rhabdomyolysis caused by the moderate CYP3A4 inhibitor fluconazole in a patient on stable atorvastatin therapy: a case report and literature review.

    Science.gov (United States)

    Hsiao, S-H; Chang, H-J; Hsieh, T-H; Kao, S-M; Yeh, P-Y; Wu, T-J

    2016-10-01

    Rhabdomyolysis is a severe potential adverse drug reaction of statin therapy. We report a case of rhabdomyolysis due to drug-drug interaction (DDI) between atorvastatin and fluconazole and review the literature. A 70-year-old woman received atorvastatin for hyperlipidaemia without any problem for 4 years. When intravenous fluconazole was added for treating a fungal infection, rhabdomyolysis developed 2 weeks later. Removal of atorvastatin led to the resolution of her rhabdomyolysis. Our case demonstrates that in some subjects even a moderate CYP3A4 inhibitor such as fluconazole may lead to rhabdomyolysis in subjects receiving a statin. © 2016 John Wiley & Sons Ltd.

  1. In Vitro Evaluation of the Type of Interaction Obtained by the Combination of Terbinafine and Itraconazole, Voriconazole, or Amphotericin B against Dematiaceous Molds▿

    Science.gov (United States)

    Biancalana, Fernanda Simas Corrêa; Lyra, Luzia; Schreiber, Angélica Zaninelli

    2011-01-01

    In vitro associations using the checkerboard microdilution method indicated lower MIC ranges and MIC median values for each drug (terbinafine, itraconazole, voriconazole, and amphotericin B) in association than those obtained for each single drug. Fractional inhibitory concentration index (FIC) results showed 100% synergism in the association of terbinafine with voriconazole, 96.5% in the association of terbinafine with amphotericin B, and 75.9% in the association of terbinafine with itraconazole. Drug combinations may be useful for treatment of dematiaceous mold infections as an alternative treatment to enhance the effectiveness of each drug. PMID:21690288

  2. Preparation of fluconazole buccal tablet and influence of formulation expedients on its properties.

    Science.gov (United States)

    Mohamed, Saifulla P; Muzzammil, Shariff; Pramod, Kumar T M

    2011-04-01

    The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis. The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment. The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method. Microcrystalline cellulose was used as the filler and its effect was also studied. The prepared dosage forms were evaluated for physicochemical properties, in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue. Tablets containing 50% of polymers (Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force, residence time and in vitro drug release. The in vitro drug release studies revealed that drug released for 8 h, which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.

  3. Reversal of fluconazole resistance induced by a synergistic effect with Acca sellowiana in Candida glabrata strains.

    Science.gov (United States)

    R M Machado, Gabriella da; Pippi, Bruna; Dalla Lana, Daiane Flores; Amaral, Ana Paula S; Teixeira, Mário Lettieri; Souza, Kellen C B de; Fuentefria, Alexandre M

    2016-11-01

    The increased incidence of non-albicans Candida (NAC) resistant to fluconazole (FLZ) makes it necessary to use new therapeutic alternatives. Acca sellowiana (O.berg) Burret (Myrtaceae) is a guava with several proven biological activities. The interaction with fluconazole can be a feasible alternative to overcome this resistance. This study evaluates the in vitro antifungal activity of fractions obtained from the lyophilized aqueous extract of the leaves of A. sellowiana against resistant strains of NAC. The antifungal activity of the fractions was evaluated at 500 μg/mL by microdilution method. Checkerboard assay was performed to determine the effect of the combination of the F2 fraction and antifungal at concentrations: MIC/4, MIC/2, MIC, MIC × 2 and MIC × 4. Candida glabrata showed the lowest MIC values (500-3.90 μg/mL) and the F2 active fraction was the most effective. The association of F2 with FLZ showed a strong synergistic effect (FICI ≤ 0.5) against 100% of C. glabrata resistant isolates. Moreover, the F2 active fraction has demonstrated that probably acts in the cell wall of these yeasts. There was no observed acute dermal toxicity of lyophilized aqueous extract of leaves of A. sellowiana on pig ear skin cells. The interaction between substances present in the F2 active fraction is possibly responsible for the antifungal activity presented by this fraction. This study is unprecedented and suggests that the combination of F2 active fraction and FLZ might be used as an alternative treatment for mucocutaneus infections caused by C. glabrata resistant.

  4. Supersaturation induced by Itraconazole/Soluplus® micelles provided high GI absorption in vivo

    Directory of Open Access Journals (Sweden)

    Yue Zhong

    2016-04-01

    Full Text Available To investigate the effect of supersaturation induced by micelle formation during dissolution on the bioavailability of itraconazole (ITZ/Soluplus® solid dispersion. Solid dispersions prepared by hot melt extrusion (HME were compressed into tablets directly with other excipients. Dissolution behavior of ITZ tablets was studied by dissolution testing and the morphology of micelles in dissolution media was studied using transmission electron microscopy (TEM. Drug transferring from stomach into intestine was simulated to obtain a supersaturated drug solution. Bioavailability studies were performed on the ITZ tablets and Sporanox® in beagle dogs. The morphology of micelles in the dissolution media was observed to be spherical in shape, with an average size smaller than 100 nm. The supersaturated solutions formed by Soluplus® micelles were stable and no precipitation took place over a period of 180 min. Compared with Sporanox®, ITZ tablets exhibited a 2.50-fold increase in the AUC(0–96 of ITZ and a 1.95-fold increase in its active metabolite hydroxyitraconazole (OH-ITZ in the plasma of beagle dogs. The results obtained provided clear evidence that not only the increase in the dissolution rate in the stomach, but also the supersaturation produced by micelles in the small intestine may be of great assistance in the successful development of poorly water-soluble drugs. The micelles formed by Soluplus® enwrapped the molecular ITZ inside the core which promoted the amount of free drug in the intestinal cavity and carried ITZ through the aqueous boundary layer (ABL, resulting in high absorption by passive transportation across biological membranes. The uptake of intact micelles through pinocytosis together with the inhibition of P-glycoprotein-mediated drug efflux in intestinal epithelia contributed to the absorption of ITZ in the gastrointestinal tract. These results indicate that HME with Soluplus®, which can induce supersaturation by micelle

  5. Fluconazole and intrathecal injection of amphotericin B for treating cryptococcal meningitis

    Institute of Scientific and Technical Information of China (English)

    Shiguang Wen; Jian Yin; Shaosen Qin; Meiping Wen; Xiaoyan Zhang; Dongke Chen

    2006-01-01

    BACKGROUND: At present, fiuconazole and intrathecal injection of amphotericin B has been widely used to treat cryptococcal meningitis. However, the application of amphotericin B can shorten course and has good effects on the treatment of cryptococcal meningitis.OBJECTIVE: To observe the effects and poor response of the intrathecal injection of amphotericin B on the treatment of cryptococcal meningitis.DESIGN: Retrospective-case analysis.SETTING: Department of Neurology, Beijing Hospital of Ministry of Public Health.PARTICIPANTS: Eight patients with cryptococcal meningitis were selected from Department of Neurology,Beijing Hospital of Ministry of Public Health from January 1995 to January 2006. Among them, there were 3 males and 5 females aged from 17 to 41 years and the course ranged from 21 days to 3 months. Patients who had symptoms of febrile and headache, positive meninges excitation, positive latex agglutination of cryptococcus of cerebrospinal fluid and positive ink smear were selected in this study. All patients provided informed consent.METHODS: Eight patients were treated with the fluconazole and intrathecal injection of amphotericin B. ①Intracranial hypertension of patients was controlled with flowing cerebrospinal fluid by repeatedly piercing waist;meanwhile, patients were taken the intrathecal injection of amphotericin B combining with flucytosine or fiuconazole treatment. The dosage of amphotericin B was 1-5 mg/d at the beginning of administration, and then, the samples were added with 2 mg dexasine and 500 mL 5% glucose solution. The dosage was increased 5.0 mg per day till 50 mg per day, and the total dosage was 3.0-4.0 g. In addition, 2 mg dexasine was mixed with 4.0-5.0 mL cerebrospinal fluid, and then the solution was gradually injected into sheath for once a week. Fluconazole was dripped into vein with the volume of 400 mg per day, and then, 14 days later,fluconazole was orally taken by patients. ② Other therapies, such as decreasing

  6. Quercetin Assists Fluconazole to Inhibit Biofilm Formations of Fluconazole-Resistant Candida Albicans in In Vitro and In Vivo Antifungal Managements of Vulvovaginal Candidiasis

    Directory of Open Access Journals (Sweden)

    Mei Gao

    2016-11-01

    Full Text Available Background: Vulvovaginal candidiasis (VVC is a common gynecological disease. Candida albicans is believed to be mainly implicated in VVC occurrence, the biofilm of which is one of the virulence factors responsible for resistance to traditional antifungal agents especially to fluconazole (FCZ. Quercetin (QCT is a dietary flavonoid and has been demonstrated to be antifungal against C. albicans biofilm. Methods: 17 C. albicans isolates including 15 clinical ones isolated from VVC patients were employed to investigate the effects of QCT and/or FCZ on the inhibition of C. albicans biofilm. Results: We observed that 64 µg/mL QCT and/or 128 µg/mL FCZ could (i be synergistic against 10 FCZ-resistant planktonic and 17 biofilm cells of C. albicans, (ii inhibit fungal adherence, cell surface hydrophobicity (CSH, flocculation, yeast-to-hypha transition, metabolism, thickness and dispersion of biofilms; (iii down-regulate the expressions of ALS1, ALS3, HWP1, SUN41, UME6 and ECE1 and up-regulate the expressions of PDE2, NRG1 and HSP90, and we also found that (iv the fungal burden was reduced in vaginal mucosa and the symptoms were alleviated in a murine VVC model after the treatments of 5 mg/kg QCT and/or 20 mg/kg FCZ. Conclusion: Together with these results, it could be demonstrated that QCT could be a favorable antifungal agent and a promising synergist with FCZ in the clinical management of VVC caused by C. albicans biofilm.

  7. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.

    NARCIS (Netherlands)

    Kullberg, B.J.; Sobel, J.D.; Ruhnke, M.; Pappas, P.G.; Viscoli, C.; Rex, J.H.; Cleary, J.D.; Rubinstein, E.; Church, L.W.; Brown, J.M.; Schlamm, H.T.; Oborska, I.T.; Hilton, F.; Hodges, M.R.

    2005-01-01

    BACKGROUND: Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients.

  8. Single-dose fluconazole versus standard 2-week therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, double-blind, double-dummy trial.

    NARCIS (Netherlands)

    Hamza, O.J.M.; Matee, M.I.N.; Bruggemann, R.J.M.; Moshi, M.J.; Simon, E.N.; Mugusi, F.; Mikx, F.H.M.; Lee, H.A.L. van der; Verweij, P.E.; Ven, A.J.A.M. van der

    2008-01-01

    BACKGROUND: Oropharyngeal candidiasis is the most common opportunistic infection affecting patients with human immunodeficiency virus (HIV) infection. Because of convenience, cost, and reluctance to complicate antiretroviral treatment regimens, single-dose fluconazole may be a favorable regimen for

  9. Fluconazole Pharmacokinetics in Galleria mellonella Larvae and Performance Evaluation of a Bioassay Compared to Liquid Chromatography-Tandem Mass Spectrometry for Hemolymph Specimens

    DEFF Research Database (Denmark)

    Astvad, Karen Marie Thyssen; Meletiadis, Joseph; Whalley, Sarah

    2017-01-01

    The invertebrate model organism Galleria mellonella can be used to assess the efficacy of treatment of fungal infection. The fluconazole dose best mimicking human exposure during licensed dosing is unknown. We validated a bioassay for fluconazole detection in hemolymph and determined...... the fluconazole pharmacokinetics and pharmacodynamics in larval hemolymph in order to estimate a humanized dose for future experiments. A bioassay using 4-mm agar wells, 20 μl hemolymph, and the hypersusceptible Candida albicans DSY2621 was established and compared to a validated liquid chromatography-tandem mass...... spectrometry (LC-MS-MS) method. G. mellonella larvae were injected with fluconazole (5, 10, and 20 mg/kg of larval weight), and hemolymph was harvested for 24 h for pharmacokinetics calculations. The exposure was compared to the human exposure during standard licensed dosing. The bioassay had a linear standard...

  10. Uso do fluconazol endovenoso no tratamento da endoftalmite fúngica endógena: relato de caso Intravenous fluconazole use in the treatment of fungic endogenous endophthalmitis: case report

    Directory of Open Access Journals (Sweden)

    Patrícia de Freitas Dotto

    2005-08-01

    Full Text Available Os autores descrevem um caso de endoftalmite endógena por Candida albicans, em recém-nascido prematuro, refratária ao tratamento com anfotericina B endovenosa e que apresentou resolução com o uso do fluconazol endovenoso. Ressaltam ainda os aspectos clínicos da endoftalmite endógena por Candida albicans por meio de revisão da literatura.The authors describe a case of endogenous Candida albicans endophthalmitis in one extremely low birth-weight newborn refractory to endovenous amphotericin B treatment that presented resolution with the use of endovenous fluconazole. Clinical aspects of endogenous Candida albicans endophthalmitis are also pointed out by a review of the literature.

  11. Comparative Evaluation of Antifungal Activity of Piper Betel Leaf Oil, Origanum vulgare Essential Oil and Fluconazole Suspension on Candida albicans − An In Vitro Study

    Directory of Open Access Journals (Sweden)

    Nisha Makkar

    2017-01-01

    Full Text Available Introduction: Oropharyngeal candidiasis is an opportunistic mucosal infection caused by Candida albicans. It usually responds to topical treatments such as clotrimazole troches, topical fluconazole, chlorhexidine mouthwash and nystatin suspension. Piper betel leaf oil and Origanum vulgare essential oil have shown some topical antifungal activity. Aim: To determine and compare the antifungal efficacy of piper betel leaf oil, O. vulgare essential oil and fluconazole suspension against C. albicans. Materials and Methods: The zone of inhibition was measured by the cup–plate diffusion method using 100 μl volume of piper betel leaf oil, O. vulgare essential oil and fluconazole suspension, which were pipetted into the wells of the inoculated Sabouraud’s dextrose agar plates. The zone of inhibition was measured in millimetres using Vernier calliper. Minimum inhibitory concentration (MIC was determined by the broth macro-dilution test by pouring 1 ml of the respective concentrations of the test material to the individual test tubes along with 10 μl of the diluted test organism inoculum. Finally, MIC was calculated using a reflective viewer. Results: The zone of inhibition for O. vulgare essential oil (>40 mm was more than fluconazole suspension (>35 mm. MIC of O. vulgare essential oil, piper betel leaf oil and fluconazole suspension was 1.6%, 0.4% and 0.8%, respectively. Conclusion: O. vulgare essential oil was found to be a more effective antifungal agent than piper betel leaf oil and fluconazole suspension.

  12. Fluconazole Pharmacokinetics in Galleria mellonella Larvae and Performance Evaluation of a Bioassay Compared to Liquid Chromatography-Tandem Mass Spectrometry for Hemolymph Specimens

    Science.gov (United States)

    Astvad, Karen Marie Thyssen; Meletiadis, Joseph; Whalley, Sarah

    2017-01-01

    ABSTRACT The invertebrate model organism Galleria mellonella can be used to assess the efficacy of treatment of fungal infection. The fluconazole dose best mimicking human exposure during licensed dosing is unknown. We validated a bioassay for fluconazole detection in hemolymph and determined the fluconazole pharmacokinetics and pharmacodynamics in larval hemolymph in order to estimate a humanized dose for future experiments. A bioassay using 4-mm agar wells, 20 μl hemolymph, and the hypersusceptible Candida albicans DSY2621 was established and compared to a validated liquid chromatography-tandem mass spectrometry (LC–MS-MS) method. G. mellonella larvae were injected with fluconazole (5, 10, and 20 mg/kg of larval weight), and hemolymph was harvested for 24 h for pharmacokinetics calculations. The exposure was compared to the human exposure during standard licensed dosing. The bioassay had a linear standard curve between 1 and 20 mg/liter. Accuracy and coefficients of variation (percent) values were below 10%. The Spearman coefficient between assays was 0.94. Fluconazole larval pharmacokinetics followed one-compartment linear kinetics, with the 24-h area under the hemolymph concentration-time curve (AUC24 h) being 93, 173, and 406 mg · h/liter for the three doses compared to 400 mg · h/liter in humans under licensed treatment. In conclusion, a bioassay was validated for fluconazole determination in hemolymph. The pharmacokinetics was linear. An exposure comparable to the human exposure during standard licensed dosing was obtained with 20 mg/kg. PMID:28760893

  13. An Evaluation of Theraphy with Fluconazole 150 mg Tablets Compared to Fluconazole 150 mg Tablets Plus Dermoxen Lenitiva Cream in The Time to Reduce Simptomatology in Women with Vulvovaginal Candidiasis

    Directory of Open Access Journals (Sweden)

    Davide Carati

    2014-06-01

    Full Text Available Aim of the study. Authors investigated first of all the time to onset of first relief of symptoms. Secondary measures included the time to overall relief of symptoms and the reoccurrence rate over the first 45 days after the first visit. Methods. A randomized, open-label, parallel study evaluated 47 women with moderate to severe symptoms of Vulvo Vaginal Candidiasis (VVC. Patients were divided into two groups of treatment: group 1 followed a therapy with Fluconazole 150 mg tablets, while group 2 had a therapy based on Fluconazole 150 mg tablets coadjuvated by Dermoxen Lenitiva cream. Results. The time at which 50% of patients experienced first relief of symptoms was 24.6 hours for Group 1, while for Group 2 it was 12.4 hours (P<0.05. There were significant differences between the two groups in respect to the time of first relief of symptoms and reoccurrence of infection within 45 days of treatment. Conclusions. Combined treatment with Fluconazole 150 mg tablets and by Dermoxen Lenitiva cream provides statistically significant improvement in the time of first relief of symptoms, complete relief of symptoms and relapse time in the treatment of VVC compared to fluconazole 150 mg tablets only.

  14. Is non-response to fluconazole maintenance therapy for recurrent Candida vaginitis related to sensitization to atopic reactions?

    Science.gov (United States)

    Donders, Gilbert G G; Grinceviciene, Svitrigaile; Bellen, Gert; Jaeger, Martin; Ten Oever, Jaap; Netea, Mihai G

    2018-04-01

    Is sensitization to atopic reaction related to treatment response of recurrent Candida vulvovaginal (RVVC)? Analysis of ReCiDiF trial data of optimal (OR) and non-responders (NR) to fluconazole maintenance treatment, to explore medical history, physical status, family history, and vaginal immune response for potential sensitization to atopic reaction. Sociodemographic characteristics of 33 NR women were not different from 38 OR. NR had received higher number of different treatments (mean difference 1.6 different treatments (95% CI: 0.20-2.97), P = .03) and had more episodes of disease (P predictive factor for non-response in multivariate analysis with specificity 77.8% and sensitivity 51.6%. Women with RVVC with vulvar excoriation, longer duration of disease, and family history of atopic disease are at increased risk not to respond to maintenance fluconazole treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Central nervous system paracoccidioidomycosis. Report of a case successfully treated with Itraconazol Paracoccidioidomicose do sistema nervoso central. Apresentação de um caso tratado com êxito com itraconazole

    Directory of Open Access Journals (Sweden)

    Luis A. VILLA

    2000-08-01

    Full Text Available Paracoccidioidomycosis (PCM is a primary pulmonary infection that often disseminates to other organs and systems. Involvement of the central nervous system (CNS is rare and due to the fact that both clinical alertness and establishment of the diagnosis are delayed, the disease progresses causing serious problems. We report here a case of neuroparacoccidioidomycosis (NPCM, observed in a 55 year-old male, who consulted due to neurological symptoms (left hemiparesis, paresthesias, right palpebral ptosis, headache, vomiting and tonic clonic seizures of a month duration. Upon physical examination, an ulcerated granulomatous lesion was observed in the abdomen. To confirm the diagnosis a stereotactic biopsy was taken; additionally, mycological tests from the ulcerated lesion and a bronchoalveolar lavage were performed. In the latter specimens, P. brasiliensis yeast cells were visualized and later on, the brain biopsy revealed the presence of the fungus. Treatment with itraconazole (ITZ was initiated but clinical improvement was unremarkable; due to the fact that the patient was taking sodium valproate for seizure control, drug interactions were suspected and confirmed by absence of ITZ plasma levels. The latter medication was changed to clonazepam and after several weeks, clinical improvement began to be noticed and was accompanied by diminishing P. brasiliensis antigen and antibody titers. In the PCM endemic areas, CNS involvement should be considered more often and the efficacy of itraconazole therapy should also be taken into consideration.A paracoccidioidomicose (PCM é infecção pulmonar primária que algumas vezes pode se disseminar a outros órgãos e sistemas. O envolvimento do sistema nervoso central (SNC é raro e devido ao fato que a alerta clínica e o estabelecimento do diagnóstico são tardios, a doença progride e o paciente piora. Aquí apresentamos caso de neuroparacoccidioidomicose (NPCM observada em homem de 55 anos de idade que

  16. A comparative study of itraconazole in various dose schedules in the treatment of pulmonary aspergilloma in treated patients of pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Prahlad Rai Gupta

    2015-01-01

    Full Text Available Introduction: The optimal dose, duration, and efficacy of itraconazole in Indian patients of pulmonary aspergilloma (PA are not clearly defined. Therefore, a study was carried out, to resolve these issues in diagnosed cases of PA complicating old treated patients of pulmonary tuberculosis. Materials and Methods: The study patients randomly received itraconazole either in a fixed dose schedule of 200 mg (group I, 200 mg twice daily (group II or a variable dose schedule (group III, for 12 months. All the patients were followed up for the entire duration of the study for clinical, radiological, and immunological response. The side effects were recorded as and when reported by the patients and managed symptomatically. Results: A total of 60 patients were enrolled, 20, in each group. There were no intergroup differences with regard to age, sex, body weight, smoking status, alcohol intake, symptoms, Potassium hydroxide (KOH mount, fungal culture, pattern of radiological lesions or anti-aspergillus antibodies (anti-Asp-Ab titers. The radiological response was poor in group I patients, as compared to the other groups, at two months (P < 0.05. The dose of itraconazole was increased in five of the patients in group I due to poor response. A higher number of group II patients suffered side effects and the dose of itraconazole had to be decreased in three of these patients, but none of the patients on a variable dose schedule required a change in dose schedule. Conclusion: Thus, a weight-based variable dose schedule of itraconazole was found to be a more effective and safer modality in the management of PA than a fixed dose schedule.

  17. Unbound fraction of fluconazole and linezolid in human plasma as determined by ultrafiltration: Impact of membrane type.

    Science.gov (United States)

    Kratzer, Alexander; Kees, Frieder; Dorn, Christoph

    2016-12-15

    Ultrafiltration is a rapid and convenient method to determine the free concentrations of drugs in plasma. Several ultrafiltration devices based on Eppendorf cups are commercially available, but are not validated for such use by the manufacturer. Plasma pH, temperature and relative centrifugal force as well as membrane type can influence the results. In the present work, we developed an ultrafiltration method in order to determine the free concentrations of linezolid or fluconazole, both neutral and moderately lipophilic antiinfective drugs for parenteral as well as oral administration, in plasma of patients. Whereas both substances behaved relatively insensitive in human plasma regarding variations in pH (7.0-8.5), temperature (5-37°C) or relative centrifugal force (1000-10.000xg), losses of linezolid were observed with the Nanosep Omega device due to adsorption onto the polyethersulfone membrane (unbound fraction 75% at 100mg/L and 45% at 0.1mg/L, respectively). No losses were observed with Vivacon which is equipped with a membrane of regenerated cellulose. With fluconazole no differences between Nanosep and Vivacon were observed. Applying standard conditions (pH 7.4/37°C/1000xg/20min), the mean unbound fraction of linezolid in pooled plasma from healthy volunteers was 81.5±2.8% using Vivacon, that of fluconazole was 87.9±3.5% using Nanosep or 89.4±3.3% using Vivacon. The unbound fraction of linezolid was 85.4±3.7% in plasma samples from surgical patients and 92.1±6.2% in ICU patients, respectively. The unbound fraction of fluconazole was 93.9±3.3% in plasma samples from ICU patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Activities of Fluconazole, Caspofungin, Anidulafungin, and Amphotericin B on Planktonic and Biofilm Candida Species Determined by Microcalorimetry

    Science.gov (United States)

    Maiolo, Elena Maryka; Furustrand Tafin, Ulrika; Borens, Olivier

    2014-01-01

    We investigated the activities of fluconazole, caspofungin, anidulafungin, and amphotericin B against Candida species in planktonic form and biofilms using a highly sensitive assay measuring growth-related heat production (microcalorimetry). C. albicans, C. glabrata, C. krusei, and C. parapsilosis were tested, and MICs were determined by the broth microdilution method. The antifungal activities were determined by isothermal microcalorimetry at 37°C in RPMI 1640. For planktonic Candida, heat flow was measured in the presence of antifungal dilutions for 24 h. Candida biofilm was formed on porous glass beads for 24 h and exposed to serial dilutions of antifungals for 24 h, and heat flow was measured for 48 h. The minimum heat inhibitory concentration (MHIC) was defined as the lowest antifungal concentration reducing the heat flow peak by ≥50% (≥90% for amphotericin B) at 24 h for planktonic Candida and at 48 h for Candida biofilms (measured also at 24 h). Fluconazole (planktonic MHICs, 0.25 to >512 μg/ml) and amphotericin B (planktonic MHICs, 0.25 to 1 μg/ml) showed higher MHICs than anidulafungin (planktonic MHICs, 0.015 to 0.5 μg/ml) and caspofungin (planktonic MHICs, 0.125 to 0.5 μg/ml). Against Candida species in biofilms, fluconazole's activity was reduced by >1,000-fold compared to its activity against the planktonic counterparts, whereas echinocandins and amphotericin B mainly preserved their activities. Fluconazole induced growth of planktonic C. krusei at sub-MICs. At high concentrations of caspofungin (>4 μg/ml), paradoxical growth of planktonic C. albicans and C. glabrata was observed. Microcalorimetry enabled real-time evaluation of antifungal activities against planktonic and biofilm Candida organisms. It can be used in the future to evaluate new antifungals and antifungal combinations and to study resistant strains. PMID:24566186

  19. Fluconazole affects the alkali-metal-cation homeostasis and susceptibility to cationic toxic compounds of Candida glabrata

    Czech Academy of Sciences Publication Activity Database

    Elicharová, Hana; Sychrová, Hana

    2014-01-01

    Roč. 160, č. 8 (2014), s. 1705-1713 ISSN 1350-0872 R&D Projects: GA ČR GAP302/12/1151; GA MŠk(CZ) ED1.1.00/02.0109 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : Candida glabrata * fluconazole * membrane potential Subject RIV: EE - Microbiology, Virology Impact factor: 2.557, year: 2014

  20. Candida albicans Swi/Snf and Mediator Complexes Differentially Regulate Mrr1-Induced MDR1 Expression and Fluconazole Resistance.

    Science.gov (United States)

    Liu, Zhongle; Myers, Lawrence C

    2017-11-01

    Long-term azole treatment of patients with chronic Candida albicans infections can lead to drug resistance. Gain-of-function (GOF) mutations in the transcription factor Mrr1 and the consequent transcriptional activation of MDR1 , a drug efflux coding gene, is a common pathway by which this human fungal pathogen acquires fluconazole resistance. This work elucidates the previously unknown downstream transcription mechanisms utilized by hyperactive Mrr1. We identified the Swi/Snf chromatin remodeling complex as a key coactivator for Mrr1, which is required to maintain basal and induced open chromatin, and Mrr1 occupancy, at the MDR1 promoter. Deletion of snf2 , the catalytic subunit of Swi/Snf, largely abrogates the increases in MDR1 expression and fluconazole MIC observed in MRR1 GOF mutant strains. Mediator positively and negatively regulates key Mrr1 target promoters. Deletion of the Mediator tail module med3 subunit reduces, but does not eliminate, the increased MDR1 expression and fluconazole MIC conferred by MRR1 GOF mutations. Eliminating the kinase activity of the Mediator Ssn3 subunit suppresses the decreased MDR1 expression and fluconazole MIC of the snf2 null mutation in MRR1 GOF strains. Ssn3 deletion also suppresses MDR1 promoter histone displacement defects in snf2 null mutants. The combination of this work with studies on other hyperactive zinc cluster transcription factors that confer azole resistance in fungal pathogens reveals a complex picture where the induction of drug efflux pump expression requires the coordination of multiple coactivators. The observed variations in transcription factor and target promoter dependence of this process may make the search for azole sensitivity-restoring small molecules more complicated. Copyright © 2017 American Society for Microbiology.

  1. Kombinationsbehandling med fluconazol og andre QTc-forlængende lægemidler forlænger QTc- intervallet

    DEFF Research Database (Denmark)

    Buch, Tina; Andersen, Stig Ejdrup

    2015-01-01

    Several drugs have a QTc-prolonging effect and are metabolized by CYP3A4. The combination of QTc-prolonging drugs may act additive of the QTc interval. The risk increases additionally by co-administration of a CYP3A4-inhibiting substrate. This case report describes an incident with QTc prolongati...... which was probably caused by an interaction induced by a combination of amiodarone, clarithromycin and the CYP3A4-inhibitor fluconazole....

  2. Drug-drug interaction and doping, part 1: an in vitro study on the effect of non-prohibited drugs on the phase I metabolic profile of toremifene.

    Science.gov (United States)

    Mazzarino, Monica; de la Torre, Xavier; Fiacco, Ilaria; Palermo, Amelia; Botrè, Francesco

    2014-05-01

    The present study was designed to provide preliminary information on the potential impact of metabolic drug-drug interaction on the effectiveness of doping control strategies currently followed by the anti-doping laboratories to detect the intake of banned agents. In vitro assays based on the use of human liver microsomes and recombinant CYP isoforms were designed and performed to characterize the phase I metabolic profile of the prohibited agent toremifene, selected as a prototype drug of the class of selective oestrogen receptor modulators, both in the absence and in the presence of medicaments (fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ranitidine, fluoxetine, paroxetine, nefazodone) not included in the World Anti-Doping Agency list of prohibited substances and methods and frequently administered to athletes. The results show that the in vitro model developed in this study was adequate to simulate the in vivo metabolism of toremifene, confirming the results obtained in previous studies. Furthermore, our data also show that ketoconazole, itraconazole, miconazole and nefazodone cause a marked modification in the production of the metabolic products (i.e. hydroxylated and carboxylated metabolites) normally selected by the anti-doping laboratories as target analytes to detect toremifene intake; moderate variations were registered in the presence of fluconazole, paroxetine and fluoxetine; while no significant modifications were measured in the presence of ranitidine and cimetidine. This evidence imposes that the potential effect of drug-drug interactions is duly taken into account in anti-doping analysis, also for a broader significance of the analytical results. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Candida tropicalis arthritis of the elbow in a patient with Ewing’s sarcoma that successfully responded to itraconazole

    Directory of Open Access Journals (Sweden)

    Seung Youn Kim

    2011-09-01

    Full Text Available Fungal infections are rarely responsible for arthritis. Few cases of fungal arthritis have been reported, even in immunocompromised hosts susceptible to low-virulence organisms. Herein, the authors report the first case of Candida tropicalis arthritis in a child with a solid tumor. A 13-year-old boy with Ewing’s sarcoma developed arthritis in his elbow during the neutropenic period after chemotherapy. Despite treatment with broad-spectrum antibiotics, his condition did not improve and serial blood cultures failed to reveal any causative organisms. After surgical drainage, culture of the joint fluid revealed the presence of C. tropicalis . Itraconazole treatment was started and after 3 months of therapy, the patient completely recovered full elbow function.

  4. Psidium guajava L. and Psidium brownianum Mart ex DC.: Chemical composition and anti - Candida effect in association with fluconazole.

    Science.gov (United States)

    Morais-Braga, Maria Flaviana B; Sales, Débora L; Carneiro, Joara Nalyda P; Machado, Antonio Júdson T; Dos Santos, Antonia Thassya L; de Freitas, Maria Audilene; Martins, Gioconda Morais de A Bezerra; Leite, Nadghia Figueiredo; de Matos, Yedda Maria L S; Tintino, Saulo R; Souza, Djair S L; Menezes, Irwin R A; Ribeiro-Filho, Jaime; Costa, José G M; Coutinho, Henrique D M

    2016-06-01

    The therapeutic combinations have been increasingly used against fungal resistance. Natural products have been evaluated in combination with pharmaceutical drugs in the search for new components able to work together in order to neutralize the multiple resistance mechanisms found in yeasts from the genus Candida. The aqueous and hydroethanolic extracts from Psidium brownianum Mart ex DC. and Psidium guajava L. species were evaluated for their potential to change the effect of commercial pharmaceutical drugs against Candida albicans and Candida tropicalis strains. The tests were performed according to the broth microdilution method. Plate readings were carried out by spectrophotometry, and the data generated the cell viability curve and IC50 of the extracts against the yeasts. A chemical analysis of all the extracts was performed for detection and characterization of the secondary metabolites. The total phenols were quantified in gallic acid eq/g of extract (GAE/g) and the phenolic composition of the extracts was determined by HPLC. Fluconazole and all extracts presented high Minimum Inhibitories Concentrations (MICs). However, when associated with the extracts at sub-inhibitory concentrations (MIC/16), fluconazole had its effect potentiated. A synergistic effect was observed in the combination of fluconazole with Psidium brownianum extracts against all Candida strains. However, for Psidium guajava extracts the synergistic effect was produced mainly against the Candida albicans LM77 and Candida tropicalis INCQS 400042 strains. The IC50 values of fluconazole ranged from 19.22 to 68.1 μg/mL when it was used alone, but from 2.2 to 45.4 μg/mL in the presence of the extracts. The qualitative chemical characterization demonstrated the presence of phenols, flavonoids and tannins among the secondary metabolites. The concentration of total phenols ranged from 49.25 to 80.77 GAE/g in the P. brownianum extracts and from 68.06 to 82.18 GAE/g in the P. guajava extracts

  5. Research of quality values and stability study of vaginal suppositories containing fluconazole and chlorhexidine digluconate

    Directory of Open Access Journals (Sweden)

    Катерина Олександрівна Бур’ян

    2015-10-01

    Full Text Available Aim of research. Stability is one of the main quality values of remedies. Biopharmaceutical properties of drugs and efficiency of pharmacodynamic and pharmacokinetic processes of active compounds in human’s organism completely depend on physico-chemical values permanence and microbiological stability of every unit of drug. The aim of research resulting in the article was to determine the main quality values stability and microbiological purity of vaginal suppositories containing fluconazole and chlorhexidine digluconate after storage under certain conditions.Materials and methods. During both storage under room temperature and keeping in cool place vaginal suppositories prepared upon hydrophilic basis were periodically verified on indicators of description, identification, average weight and homogeneity of weight, dissolution, microbiological purity and active ingredients assay in unit dose. All research tests were carried out in accordance with both the SPhU requirements and elaborated draft of quality control procedures for «Flugedyn» remedy.Results. As a result of quality values study of suppositories test samples the efficiency and reliability of developed techniques and normative documentation draft of remedy were confirmed. Samples have been kept for as long as 5 years don’t comply with the requirements of normative documentation of remedy.Conclusion. Thus, summation of research data allow recommend following optimal storage period for vaginal suppositories «Flugedyn»: keep 3 years in dry place at a temperature 2 to 25 оС

  6. Hydrogen ADPs with Cu Kα data? Invariom and Hirshfeld atom modelling of fluconazole.

    Science.gov (United States)

    Orben, Claudia M; Dittrich, Birger

    2014-06-01

    For the structure of fluconazole [systematic name: 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol] monohydrate, C13H12F2N6O·H2O, a case study on different model refinements is reported, based on single-crystal X-ray diffraction data measured at 100 K with Cu Kα radiation to a resolution of sin θ/λ of 0.6 Å(-1). The structure, anisotropic displacement parameters (ADPs) and figures of merit from the independent atom model are compared to `invariom' and `Hirshfeld atom' refinements. Changing from a spherical to an aspherical atom model lowers the figures of merit and improves both the accuracy and the precision of the geometrical parameters. Differences between results from the two aspherical-atom refinements are small. However, a refinement of ADPs for H atoms is only possible with the Hirshfeld atom density model. It gives meaningful results even at a resolution of 0.6 Å(-1), but requires good low-order data.

  7. Efficacy of the clinical agent VT-1161 against fluconazole-sensitive and -resistant Candida albicans in a murine model of vaginal candidiasis.

    Science.gov (United States)

    Garvey, E P; Hoekstra, W J; Schotzinger, R J; Sobel, J D; Lilly, E A; Fidel, P L

    2015-09-01

    Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 and MIC90 of 0.12 μg/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC50 of 8 and MIC90 of 64 μg/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters/kg), high oral absorption (73%), and a long half-life (>48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (P < 0.0001). Similar VT-1161 efficacy was measured when an isolate highly resistant to fluconazole (MIC of 64 μg/ml) but fully sensitive in vitro to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 μg/ml) and moderately resistant to fluconazole (MIC of 8 μg/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 μg/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the in vitro MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

    Science.gov (United States)

    Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

    2010-01-01

    Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears

  9. Método de difusión con discos para la determinación de sensibilidad a fluconazol en aislamientos de Candida spp Disk diffusion method for fluconazole susceptibility testing of Candida spp. isolates

    Directory of Open Access Journals (Sweden)

    L. Rodero

    2006-09-01

    Full Text Available Se estudiaron 1193 aislamientos clínicos para estandarizar y evaluar un método de difusión con discos de fluconazol de lectura visual, que permita detectar levaduras sensibles al antifúngico. Las especies analizadas fueron: Candida albicans (n=584, Candida parapsilosis (n=196, Candida tropicalis (n=200, Candida glabrata (n=113, Candida krusei (n=50, Candida spp. y otras levaduras oportunistas (n=50. Los discos fueron manufacturados en el INEI-ANLIS "Dr. Carlos G. Malbrán". Se midieron los halos de inhibición del crecimiento producidos por fluconazol y la concentración inhibitoria mínima (CIM por el método de referencia M27-A2 modificado por EUCAST. Se establecieron los valores de corte del método de difusión en: ≥16 mm para levaduras sensibles a fluconazol (CIM ≤ 8 µg/ml, entre 9 y 15 mm para sensibles dependientes de la dosis (CIM = 16-32 mg/ml y ≤ 8 mm para resistentes (CIM ≥ 64 µg/ml. El método de difusión tuvo 94,7% de concordancia con el de referencia, con 0,2% de errores very major y 0,3% de errores major. La reproducibilidad inter e intralaboratorio fue muy buena. Para detectar aislamientos sensibles a fluconazol, este método resulta confiable y de bajo costo; sin embargo, es conveniente que los aislamientos con halos ≤ 15 mm sean reevaluados por el método de referencia.In order to standardize and evaluate a disk diffusion method with visual reading to detect in vitro fluconazole susceptibility of yeast, 1193 clinical isolates were tested. These included 584 Candida albicans, 196 Candida parapsilosis, 200 Candida tropicalis, 113 Candida glabrata, 50 Candida krusei and 50 Candida spp. and other opportunistic yeasts. The disks were manufactured in the INEI-ANLIS "Dr. Carlos G. Malbrán". The disk diffusion method results were compared to MIC results obtained by the reference CLSI M27-A2 broth microdilution method modified by EUCAST. The interpretative breakpoints for in vitro susceptibility testing of fluconazole

  10. Role of chitosan on controlling the characteristics and antifungal activity of bioadhesive fluconazole vaginal tablets

    Directory of Open Access Journals (Sweden)

    Rawan A. Fitaihi

    2018-02-01

    Full Text Available Vaginal fluconazole (FLZ prolonged release tablets containing chitosan in physical blends with other bioadhesive polymers were designed. Chitosan was mixed with hydroxypropyl methylcellulose (HPMC, guar gum or sodium carboxymethyl cellulose (NaCMC at different ratios and directly compressed into tablets. In-vitro release profiles of FLZ were monitored at pH 4.8. Compressing chitosan with HPMC at different ratios slowed FLZ release, however, time for 80% drug release (T80 did not exceed 4.3 h for the slowest formulation (F11. Adding of chitosan to guar gum at 1:2 ratio (F3 showed delayed release with T80 17.4 h while, in presence of PVP at 1:2:1 ratio (F5, T80 was 8.8 h. A blend of chitosan and NaCMC at 1:2 ratio (F15 showed prolonged drug release with T80 11.16 h. Formulations F5 and F15 showed fair physical characteristics for the powder and tablets and were subjected to further studies. Fast swelling was observed for F15 that reached 1160.53 ± 13.02% in 4 h with 2 h bioadhesion time to mouse peritoneum membrane compared with 458.83 ± 7.09% swelling with bioadhesion time exceeding 24 h for F5. Extensive swelling of F15 could indicate possible dehydration effect on vaginal mucosa. Meanwhile, antifungal activity against C. albicans was significantly high for F5.

  11. Analysis of the repaglinide concentration increase produced by gemfibrozil and itraconazole based on the inhibition of the hepatic uptake transporter and metabolic enzymes.

    Science.gov (United States)

    Kudo, Toshiyuki; Hisaka, Akihiro; Sugiyama, Yuichi; Ito, Kiyomi

    2013-02-01

    The plasma concentration of repaglinide is reported to increase greatly when given after repeated oral administration of itraconazole and gemfibrozil. The present study analyzed this interaction based on a physiologically based pharmacokinetic (PBPK) model incorporating inhibition of the hepatic uptake transporter and metabolic enzymes involved in repaglinide disposition. Firstly, the plasma concentration profiles of inhibitors (itraconazole, gemfibrozil, and gemfibrozil glucuronide) were reproduced by a PBPK model to obtain their pharmacokinetic parameters. The plasma concentration profiles of repaglinide were then analyzed by a PBPK model, together with those of the inhibitors, assuming a competitive inhibition of CYP3A4 by itraconazole, mechanism-based inhibition of CYP2C8 by gemfibrozil glucuronide, and inhibition of organic anion transporting polypeptide (OATP) 1B1 by gemfibrozil and its glucuronide. The plasma concentration profiles of repaglinide were well reproduced by the PBPK model based on the above assumptions, and the optimized values for the inhibition constants (0.0676 nM for itraconazole against CYP3A4; 14.2 μM for gemfibrozil against OATP1B1; and 5.48 μM for gemfibrozil glucuronide against OATP1B1) and the fraction of repaglinide metabolized by CYP2C8 (0.801) were consistent with the reported values. The validity of the obtained parameters was further confirmed by sensitivity analyses and by reproducing the repaglinide concentration increase produced by concomitant gemfibrozil administration at various timings/doses. The present findings suggested that the reported concentration increase of repaglinide, suggestive of synergistic effects of the coadministered inhibitors, can be quantitatively explained by the simultaneous inhibition of the multiple clearance pathways of repaglinide.

  12. Time-kill assay and Etest evaluation for synergy with polymyxin B and fluconazole against Candida glabrata.

    Science.gov (United States)

    Pankey, George; Ashcraft, Deborah; Kahn, Heather; Ismail, Abdulrahim

    2014-10-01

    Fluconazole-resistant Candida glabrata is an emerging pathogen that causes fungemia. Polymyxin B, a last-resort antibiotic used to treat multidrug-resistant Gram-negative bacterial infections, has been found to possess in vitro fungicidal activity and showed synergy with fluconazole against a single strain of C. glabrata. Since both agents may be used simultaneously in intensive care unit (ICU) patients, this study was performed to test for possible synergy of this combination against 35 C. glabrata blood isolates, using 2 methods: a time-kill assay and an experimental MIC-MIC Etest method. Thirty-five genetically unique C. glabrata bloodstream isolates were collected from 2009 to 2011, identified using an API 20C system, and genotyped by repetitive sequence-based PCR (rep-PCR). MICs were determined by Etest and broth microdilution methods. Synergy testing was performed using a modified bacterial Etest synergy method and time-kill assay, with final results read at 24 h. The Etest method showed synergy against 19/35 (54%) isolates; the time-kill assay showed synergy against 21/35 (60%) isolates. Isolates not showing drug synergy had an indifferent status. Concordance between methods was 60%. In vitro synergy of polymyxin B and fluconazole against the majority of C. glabrata isolates was demonstrated by both methods. The bacterial Etest synergy method adapted well when used with C. glabrata. Etest was easier to perform than time-kill assay and may be found to be an acceptable alternative to time-kill assay with antifungals. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  13. In vitro and in vivo susceptibility of two-drug and three-drug combinations of terbinafine, itraconazole, caspofungin, ibuprofen and fluvastatin against Pythium insidiosum.

    Science.gov (United States)

    Argenta, Juliana S; Alves, Sydney H; Silveira, Flávio; Maboni, Grazieli; Zanette, Régis A; Cavalheiro, Ayrton S; Pereira, Patrique L; Pereira, Daniela I B; Sallis, Elisa S V; Pötter, Luciana; Santurio, Janio M; Ferreiro, Laerte

    2012-05-25

    The present study investigated the in vitro inhibitory activity of terbinafine, itraconazole, caspofungin, fluvastatin and ibuprofen against 15 isolates of Pythium insidiosum in double and triple combinations and determined in vivo correlations using rabbits with experimental pythiosis. The minimal inhibitory concentration (MIC) was determined in accordance with the Clinical and Laboratory Standards Institute M 38-A2 protocol (2008), and the in vitro interactions were evaluated using a checkerboard microdilution method. For the in vivo study, 20 rabbits inoculated with P. insidiosum zoospores were divided into four groups: group 1 was treated with terbinafine and itraconazole; group 2 was treated with terbinafine, itraconazole and fluvastatin; group 3 was treated with terbinafine and caspofungin; and group 4 was the control group. Combinations of terbinafine with caspofungin or ibuprofen were synergistic for 47% of the isolates, and antagonism was not observed in any of the double combinations. The triple combinations were mostly indifferent, but synergism and antagonism were also observed. In the in vivo study, the histological aspect of the lesions was similar among the groups, but group 2 showed the lowest amount of hyphae and differed significantly from the other groups. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Randomized, double-blind, comparative study on efficacy and safety of itraconazole pulse therapy and terbinafine pulse therapy on nondermatophyte mold onychomycosis: A study with 90 patients.

    Science.gov (United States)

    Ranawaka, Ranthilaka R; Nagahawatte, Ajith; Gunasekara, Thusitha Aravinda; Weerakoon, Hema S; de Silva, S H Padmal

    2016-08-01

    Nondermatophyte mold (NDM) onychomycosis shows poor response to current topical, oral or device-related antifungal therapies. This study was aimed to determine the efficacy and safety of itraconazole and terbinafine pulse therapy on NDM onychomycosis. Mycologically proven subjects were treated with itraconazole 400 mg daily or terbinafine 500 mg daily for 7 days/month; two pulses for fingernails and three pulses for toenails(SLCTR/2013/013). One-hundred seventy-eight patients underwent mycological studies and 148 had positive fungal isolates. NDM were the prevailing fungi, 68.2%, followed by candida species 21.6%, and dermatophytes made up only 10.1%. Out of NDM Aspergillus spp (75.1%) predominated followed by 8.9% Fusarium spp and 4.95% Penicillium spp. The clinical cure at completion of pulse therapy was statistically significant 9.2% versus 2.0% (p terbinafine pulse cured 55.0% Aspergillus spp and 50.0% Fusarium spp. NDM was the prevailing fungi in onychomycosis in Sri Lanka. Both itraconazole and terbinafine were partially effective on NDM onychomycosis showing a clinical cure of 54-65%. Future research should focus on searching more effective antifungal for NDM onychomycosis.

  15. In vitro Susceptibility of Fluconazole, Clotrimazole and Toucrium Polium Smoke Product on Candida Isolates of Vaginal Candidiasis

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    B Bonyadpour

    2009-07-01

    Full Text Available ABSTRACT: Introduction & Objective: It has been estimated that up to 75% of women in their child-bearing age have been affected by vulvovaginal candidiasis at least once in their life time. Almost 45% of women experience this infection two or more times. The antifungal azole group, in topical and oral forms, is the common way of therapy. Herbal products are often used for vulvovaginal therapy. Nowadays, Toucrium polium (TP products are being used as traditional medicine to reduce signs of Candida vaginitis. There is no study regarding to antifungal activity of TP smoke product in Iran. The aim of this study was to evaluate the In vitro activity of TP smoke product against Candida, isolated from women with Candida vaginitis, compared with antifungal drugs which are ordinary used to cure Candida vaginitis. Materials & Methods: The present study was conducted at the University of Medical Sciences of Shiraz in 1387 (2008. During seven months, samples were taken from 450 patients suffering from urogenital infections and 105 Candida vaginitis were detected. Germ tube test was used for identification of fungal species. TP smoke product was prepared in suitable potency. Antifungal activity of fluconazole, clotrimazole and TP product were evaluated by disk diffusion method. Sterile blank disks were loaded by TP smoke product in potency of 10-240 microliter/disk. Inhibition zone around the disks were measured and compared with each other. Results: 105 Candida species were isolated from the patients. Candida species were identified by germ tube test as Candida albicans 74 (70.5% and Candida non-albicans 31(29.5%.The mean of inhibition zone around the clotrimazole disks was 22±5.39 along with one case of resistance. Forty seven species had resistance to fluconazole while 94% and 55.2.% of all samples were sensitive to clotrimazole and fluconazole respectively. All of the clinical isolates and standard Candida species were sensitive to TP smoke product

  16. The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans.

    Science.gov (United States)

    Shao, Jing; Zhang, MengXiang; Wang, TianMing; Li, Yue; Wang, ChangZhong

    2016-01-01

    Fungal infections caused by fluconazole-resistant Candida albicans are an intractable clinical problem, calling for new efficient antifungal drugs. Kaempferol, an active flavonoid, has been considered a potential candidate against Candida species. This work investigates the resistance reversion of kaempferol in fluconazole-resistant C. albicans and the underlying mechanism. The antifungal activities of fluconazole and/or kaempferol were assessed by a series of standard procedures including broth microdilution method, checkerboard assay and time-kill (T-K) test in nine clinical strains as well as a standard reference isolate of C. albicans. Subsequently, the morphological changes, the efflux of rhodamine 6G, and the expressions of CDR 1, CDR 2, and MDR 1 were analysed by scanning electron microscope (SEM), inverted fluorescence microscope and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans z2003. For all the tested C. albicans strains, the minimum inhibitory concentrations (MICs) of fluconazole and kaempferol ranged 0.25-32 and 128-256 μg/mL with a range of fractional inhibitory concentration index of 0.257-0.531. In C. albicans z2003, the expression of both CDR 1 and CDR 2 were decreased after exposure to kaempferol alone with negligible rhodamine 6G accumulation, while the expression of CDR 1, CDR 2 and MDR 1 were all decreased when fluconazole and kaempferol were used concomitantly with notable fluorescence of rhodamine 6G observed. Kaempferol-induced reversion in fluconazole-resistant C. albicans might be likely due to the suppression of the expression of CDR1, CDR2 and MDR1.

  17. Influence of formulation and processing variables on properties of itraconazole nanoparticles made by advanced evaporative precipitation into aqueous solution.

    Science.gov (United States)

    Bosselmann, Stephanie; Nagao, Masao; Chow, Keat T; Williams, Robert O

    2012-09-01

    Nanoparticles, of the poorly water-soluble drug, itraconazole (ITZ), were produced by the Advanced Evaporative Precipitation into Aqueous Solution process (Advanced EPAS). This process combines emulsion templating and EPAS processing to provide improved control over the size distribution of precipitated particles. Specifically, oil-in-water emulsions containing the drug and suitable stabilizers are sprayed into a heated aqueous solution to induce precipitation of the drug in form of nanoparticles. The influence of processing parameters (temperature and volume of the heated aqueous solution; type of nozzle) and formulation aspects (stabilizer concentrations; total solid concentrations) on the size of suspended ITZ particles, as determined by laser diffraction, was investigated. Furthermore, freeze-dried ITZ nanoparticles were evaluated regarding their morphology, crystallinity, redispersibility, and dissolution behavior. Results indicate that a robust precipitation process was developed such that size distribution of dispersed nanoparticles was shown to be largely independent across the different processing and formulation parameters. Freeze-drying of colloidal dispersions resulted in micron-sized agglomerates composed of spherical, sub-300-nm particles characterized by reduced crystallinity and high ITZ potencies of up to 94% (w/w). The use of sucrose prevented particle agglomeration and resulted in powders that were readily reconstituted and reached high and sustained supersaturation levels upon dissolution in aqueous media.

  18. ACTIVIDAD ANTIMICÓTICA DEL ACEITE ESENCIAL DE LAS HOJAS DE Minthostachys mollis (MUÑA COMPARADO CON EL FLUCONAZOL EN CULTIVO DE Candida albicans

    Directory of Open Access Journals (Sweden)

    Katherine M Alcalá-Marcos

    2011-01-01

    Full Text Available Objetivo.- Demostrar el efecto antimicótico del aceite esencial de las hojas de Minthostachys mollis (muña en comparación con el Fluconazol en cultivo de Candida albicans. Materiales y Método.- Estudio experimental. El efecto antimicótico se estudió midiendo 80 halos de inhibición distribuidos en 5 grupos mediante el método Kirby-Bauer. Se utilizó una cepa clínica de Candida albicans. Los grupos de estudio fueron grupo muña 25% (GM25%, grupo muña 50% (GM50%, grupo muña 100% (GM100%, un grupo control positivo (Fluconazol, y un grupo control negativo (aceite mineral. El análisis estadístico se realizó mediante la Prueba de Kruskal-Wallis y el Test de Dunn usando el paquete SPSS v.17.0. Se consideró un nivel de significancia 0,05.Conclusión.- El aceite esencial de las hojas de Minthostachys mollis (al 100% tuvo mayor efecto contra la Candida albicans que el Fluconazol; además, el efecto antimicótico del Fluconazol fue mayor que la Minthostachys mollis al 25%, y fue el mismo que la Minthostachys mollis al 50%.

  19. Actividad antimicótica del aceite esencial de las hojas de Minthostachys mollis (muña comparado con el Fluconazol en cultivo de Candida albicans

    Directory of Open Access Journals (Sweden)

    Katherine M Alcalá-Marcos

    2012-09-01

    Full Text Available Objetivo.- Demostrar el efecto antimicótico del aceite esencial de las hojas de Minthostachys mollis (muña en comparación con el Fluconazol en cultivo de Candida albicans. Materiales y Método.- Estudio experimental. El efecto antimicótico se estudió midiendo 80 halos de inhibición distribuidos en 5 grupos mediante el método Kirby-Bauer. Se utilizó una cepa clínica de Candida albicans. Los grupos de estudio fueron grupo muña 25% (GM25%, grupo muña 50% (GM50%, grupo muña 100% (GM100%, un grupo control positivo (Fluconazol, y un grupo control negativo (aceite mineral. El análisis estadístico se realizó mediante la Prueba de Kruskal-Wallis y el Test de Dunn usando el paquete SPSS v.17.0. Se consideró un nivel de significancia  0,05.Conclusión.- El aceite esencial de las hojas de Minthostachys mollis (al 100% tuvo mayor efecto contra la Candida albicans que el Fluconazol; además, el efecto antimicótico del Fluconazol fue mayor que la Minthostachys mollis al 25%, y fue el mismo que la Minthostachys mollis al 50%.

  20. Antifungal prophylaxis with fluconazole in allogeneic stem cell transplantation recipients who had prior invasive aspergillosis with subsequent complete resolution by computed tomography.

    Science.gov (United States)

    Akahoshi, Yu; Kimura, Shun-Ichi; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Kanda, Yoshinobu

    2018-04-01

    Consensus has yet to be reached regarding secondary prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT) with a complete resolution of invasive aspergillosis (IA) confirmed by chest computed tomography (CT). We retrospectively evaluated the feasibility of antifungal prophylaxis with fluconazole in allogeneic HSCT recipients who had previously developed IA which showed complete resolution as confirmed by chest CT before HSCT. Consecutive adult patients who underwent allogeneic HSCT at our institution and who had received fluconazole as systemic antifungal prophylaxis from June 2007 to January 2015 were included. We compared the clinical outcomes between patients with a past history of IA who showed a complete resolution of chest CT abnormalities (n = 13) and those without a previous history of IA (n = 137). The cumulative incidence of proven or probable IA was 8.8% in the group without a past history of IA and 0.0% in the group with a past history of IA (p = .268). The cumulative incidence of proven or probable invasive fungal disease (IFD) within 100 days after allogeneic HSCT was 10.9% in the group without a past history of IA and 15.4% in the group with a past history of IA (p = .647). Fluconazole was switched to anti-mould agents in two-thirds of the patients in each group by day 100 after HSCT. Fluconazole was confirmed to be an acceptable prophylactic agent early after allogeneic HSCT in appropriately selected patients.

  1. Species distribution and susceptibility profile to fluconazole, voriconazole and MXP-4509 of 551 clinical yeast isolates from a Romanian multi-centre study

    NARCIS (Netherlands)

    Minea, B; Nastasa, V; Moraru, R F; Kolecka, A; Flonta, M M; Marincu, I; Man, A; Toma, F; Lupse, M; Doroftei, B; Marangoci, N; Pinteala, M; Boekhout, T; Mares, M

    This is the first multi-centre study regarding yeast infections in Romania. The aim was to determine the aetiological spectrum and susceptibility pattern to fluconazole, voriconazole and the novel compound MXP-4509. The 551 isolates were identified using routine laboratory methods, matrix-assisted

  2. Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients : data of a prematurely stopped clinical trial

    NARCIS (Netherlands)

    Timmers, G J; Zweegman, S; Simoons-Smit, A M; van Loenen, A C; Touw, D; Huijgens, P C

    We conducted an open label, randomised clinical trial to compare amphotericin B colloidal dispersion (ABCD, Amphocil) 2 mg/kg/day intravenously with fluconazole 200 mg/day orally, for the prevention of fungal disease in neutropenic patients with haematological malignancies. In the event of

  3. In vitro/in vivo performance of different complexes of itraconazole used in the treatment of vaginal candidiasis

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    Mohammad Aamir Mirza

    2012-12-01

    Full Text Available A large majority of new chemical entities and many existing drug molecules exhibit poor aqueous solubility, which may limit their potential use in developing drug formulations, with optimum bioavailability. One of the approaches to improve the solubility of a poorly water soluble drug and eventually its bioavailability is complexation with agents like humic acid (HA, fulvic acid (FA, β-cyclodextrin (β-CD, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD and caffeine (Caff. The current work emphasized at employing these agents to prepare different complexes and their in vitro/in vivo assessment. All the complexes evaluated for their complexation efficiency and authenticated by molecular modeling; conformational analysis, differential scanning calorimetry (DSC, X-ray diffraction (XRD, nuclear magnetic resonance (NMR and mass spectroscopy. Furthermore, the complexes were assessed in an in vivo, rat vaginal model for their efficacy in treatment of vaginal candidiasis. Amongst the five tested complexes, fulvic acid-itraconazole complex yielded better solubility as well as in vivo efficacy and therefore may further be explored for developing a commercial formulation for treating vaginal candidiasis.A maioria das novas entidades químicas e muitas moléculas de fármacos existentes apresenta fraca solubilidade em água, o que pode limitar seu uso potencial no desenvolvimento de formulações com biodisponibilidade ideal. Uma das abordagens para melhorar a solubilidade de um fármaco pouco solúvel em água e, eventualmente, a sua biodisponibilidade é a complexação com agentes como o ácido húmico (HA, ácido fúlvico (FA, β-ciclodextrina (β-CD, 2-hidroxipropil-β-ciclodextrina (HP-β-CD e cafeína (Caff. O presente trabalho baseia-se no uso desses agentes para preparar diferentes complexos e suas avaliações in vitro/in vivo. Todos os complexos foram avaliados quanto à eficiência de complexação por modelação molecular, análise conformacional

  4. Amphotericin B, alone or followed by itraconazole therapy, is effective in the control of experimental disseminated sporotrichosis by Sporothrix brasiliensis.

    Science.gov (United States)

    Ishida, Kelly; de Castro, Rafaela Alves; Borba Dos Santos, Luana Pereira; Quintella, Leonardo Pereira; Lopes-Bezerra, Leila M; Rozental, Sonia

    2015-01-01

    Sporothrix brasiliensis is a highly virulent member of the S. schenckii complex, which is responsible for the emergence of the epidemic sporotrichosis in southeastern Brazil over the last two decades. There are no in vivo studies on the sensitivity of S. brasiliensis to the therapeutic regimens used to treat sporotrichosis. Here, we evaluated the efficacy and safety of antifungal treatments against S. brasiliensis using a murine model of disseminated sporotrichosis. In vitro, S. brasiliensis yeasts were sensitive to low concentrations of amphotericin B-deoxycholate (AMB-d) and itraconazole (ITZ), the latter having greater selectivity toward the fungus. The following treatment regimens were tested in vivo: intravenous AMB-d for 7 days post-infection (p.i.), oral ITZ for up to 30 days p.i., and AMB-d followed by ITZ (AMB-d/ITZ). AMB-d and AMB-d/ITZ led to 100% survival of infected mice at the end of the 45-day experimental period. Although all treatments extended mice survival, only AMB-d and AMB-d/ITZ significantly reduced fungal load in all organs, but AMB-d/ITZ led to a more consistent decrease in overall fungal burden. No treatment increased the levels of serum toxicity biomarkers. Taken together, our results indicate that AMB-d/ITZ is the best therapeutic option for controlling disseminated sporotrichosis caused by S. brasiliensis. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. In-depth 2-DE reference map of Aspergillus fumigatus and its proteomic profiling on exposure to itraconazole.

    Science.gov (United States)

    Gautam, Poonam; Mushahary, Dolly; Hassan, Wazid; Upadhyay, Santosh Kumar; Madan, Taruna; Sirdeshmukh, Ravi; Sundaram, Curam Sreenivasacharlu; Sarma, Puranam Usha

    2016-07-01

    Aspergillus fumigatus (A. fumigatus) is a medically important opportunistic fungus that may lead to invasive aspergillosis in humans with weak immune system. Proteomic profiling of this fungus on exposure to itraconazole (ITC), an azole antifungal drug, may lead to identification of its molecular targets and better understanding on the development of drug resistance against ITC in A. fumigatus. Here, proteome analysis was performed using 2-DE followed by mass spectrometric analysis which resulted in identification of a total of 259 unique proteins. Further, proteome profiling of A. fumigatus was carried out on exposure to ITC, 0.154 μg/ml, the minimum inhibitory concentration (MIC50). Image analysis showed altered levels of 175 proteins (66 upregulated and 109 downregulated) of A. fumigatus treated with ITC as compared to the untreated control. Peptide mass fingerprinting led to the identification of 54 proteins (12 up-regulated and 42 down-regulated). The differentially expressed proteins include proteins related to cell stress, carbohydrate metabolism and amino acid metabolism. We also observed four proteins, including nucleotide phosphate kinase (NDK), that are reported to interact with calcineurin, a protein involved in regulation of cell morphology and fungal virulence. Comparison of differentially expressed proteins on exposure to ITC with artemisinin (ART), an antimalarial drug with antifungal activity(1), revealed a total of 26 proteins to be common among them suggesting that common proteins and pathways are targeted by these two antifungal agents. The proteins targeted by ITC may serve as important leads for development of new antifungal drugs. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan.

    Science.gov (United States)

    Mikamo, Hiroshige; Matsumizu, Miyako; Nakazuru, Yoshiomi; Okayama, Akifumi; Nagashima, Masahito

    2015-07-01

    Vulvovaginal candidiasis is the second most common cause of vaginal infections following bacterial vaginosis. For the treatment of vulvovaginal candidiasis, antifungal agents are used either as topical (vaginal tablets and cream) or oral formulations. A single oral 150 mg dose of fluconazole has been recommended as the standard therapy for uncomplicated, acute vulvovaginal candidiasis in global guidelines; however, in Japan oral fluconazole therapy has not been approved. We conducted a phase 3 study to evaluate the efficacy and safety of a single oral 150 mg dose of fluconazole in Japanese subjects with vulvovaginal candidiasis for regulatory submission. A total of 157 subjects received a single oral 150 mg dose of fluconazole. Candida species (104 strains) were identified by fungal culture from 102 subjects at baseline, including Candida albicans (100 strains). The efficacy rate for the therapeutic outcome (assessed based on a comprehensive evaluation of the clinical and mycological efficacy in each subject) was 74.7% (74/99) on Day 28 in the modified Intent-To-Treat (m-ITT) population. Concerning the clinical and mycological efficacy on Day 28 in the m-ITT population, the cure, cure or improvement, and eradication rates were 81.6%, 95.9%, and 85.9%, respectively. The most common treatment-related adverse events were diarrhea and nausea (1.9% for each). No clinically significant safety issues were reported. A single oral 150 mg dose of fluconazole demonstrated excellent therapeutic efficacy and was well tolerated in Japanese subjects with vulvovaginal candidiasis. NCT01806623. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Sensibilidad a fluconazol y voriconazol de aislamientos de Candida spp., obtenidos de mucosa oral de pacientes con sida

    OpenAIRE

    Gutiérrez, Carolina; de Bedout, Catalina; Tobón, Angela María; Cano, Luz Elena; Arango, Myrtha; Tabares, Angela María; Restrepo, Angela

    2007-01-01

    Se determinó la sensibilidad al fluconazol y al voriconazol de aislamientos de Candida spp. obtenidos de la mucosa oral de 54 pacientes con sida hospitalizados en la ESE Hospital La María (Medellín, Colombia). Además, se comprobó la especie de tales aislamientos. Los pacientes eran todos adultos (promedio de 40,5 años, rango de 23 a 56) y la mayoría (77,8%) hombres. En 40 (71,1%) de ellos se obtuvo crecimiento de Candida spp. y en 6 (11,1%) se aisló más de una especie de Candida. La clasifica...

  8. Candidacidal Activity of a Novel Killer Toxin from Wickerhamomyces anomalus against Fluconazole-Susceptible and -Resistant Strains

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    Laura Giovati

    2018-02-01

    Full Text Available The isolation and characterization from the sand fly Phlebotomus perniciosus of a Wickerhamomyces anomalus yeast strain (Wa1F1 displaying the killer phenotype was recently reported. In the present work, the killer toxin (KT produced by Wa1F1 was purified and characterized, and its antimicrobial activity in vitro was investigated against fluconazole- susceptible and -resistant clinical isolates and laboratory strains of Candida albicans and C. glabrata displaying known mutations. Wa1F1-KT showed a differential killing ability against different mutant strains of the same species. The results may be useful for the design of therapeutic molecules based on Wa1F1-KT and the study of yeast resistance mechanisms.

  9. Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis.

    Science.gov (United States)

    Rençber, Seda; Karavana, Sinem Yaprak; Yılmaz, Fethiye Ferda; Eraç, Bayri; Nenni, Merve; Özbal, Seda; Pekçetin, Çetin; Gurer-Orhan, Hande; Hoşgör-Limoncu, Mine; Güneri, Pelin; Ertan, Gökhan

    2016-01-01

    This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT(®) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis.

  10. Upper limb artery segmental occlusions due to chronic use of ergotamine combined with itraconazole, treated by thrombolysis

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    Nodari Franco

    2011-08-01

    Full Text Available Abstract Background The ergotamine tartrate associated with certain categories of drugs can lead to critical ischemia of the extremities. Discontinuation of taking ergotamine is usually sufficient for the total regression of ischemia, but in some cases it could be necessary thrombolytic and anticoagulant therapy to avoid amputation. Case report A woman of 62 years presented with a severe pain left forearm appeared 10 days ago, with a worsening trend. The same symptoms appeared after 5 days also in the right forearm. Physical examination showed the right arm slightly hypothermic, with radial reduced pulse in presence of reduced sensitivity. The left arm was frankly hypothermic, pulse less on radial and with an ulnar humeral reduced pulse, associated to a decreased sensitivity and motility. Clinical history shows a chronic headache for which the patient took a daily basis for years Cafergot suppository (equivalent to 3.2 mg of ergotamine. From about ten days had begun therapy with itraconazole for vaginal candidiasis. The Color-Doppler ultrasound shown arterial thrombosis of the upper limbs (humeral and radial bilateral, with minimal residual flow to the right and no signal on the humeral and radial left artery. Results Angiography revealed progressive reduction in size of the axillary artery and right humeral artery stenosis with right segmental occlusions and multiple hypertrophic collateral circulations at the elbow joint. At the level of the right forearm was recognizable only the radial artery, decreased in size. Does not recognize the ulnar, interosseous artery was thin. To the left showed progressive reduction in size of the distal subclavian and humeral artery, determined by multiple segmental steno-occlusion with collateral vessels serving only a thin hypotrophic interosseous artery. Arteriographic findings were compatible with systemic drug-induced disease. The immediate implementation of thrombolysis, continued for 26 hours, with

  11. Rapid detection of ERG11 gene mutations in clinical Candida albicans isolates with reduced susceptibility to fluconazole by rolling circle amplification and DNA sequencing

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    Ellis David

    2009-08-01

    Full Text Available Abstract Background Amino acid substitutions in the target enzyme Erg11p of azole antifungals contribute to clinically-relevant azole resistance in Candida albicans. A simple molecular method for rapid detection of ERG11 gene mutations would be an advantage as a screening tool to identify potentially-resistant strains and to track their movement. To complement DNA sequencing, we developed a padlock probe and rolling circle amplification (RCA-based method to detect a series of mutations in the C. albicans ERG11 gene using "reference" azole-resistant isolates with known mutations. The method was then used to estimate the frequency of ERG11 mutations and their type in 25 Australian clinical C. albicans isolates with reduced susceptibility to fluconazole and in 23 fluconazole-susceptible isolates. RCA results were compared DNA sequencing. Results The RCA assay correctly identified all ERG11 mutations in eight "reference" C. albicans isolates. When applied to 48 test strains, the RCA method showed 100% agreement with DNA sequencing where an ERG11 mutation-specific probe was used. Of 20 different missense mutations detected by sequencing in 24 of 25 (96% isolates with reduced fluconazole susceptibility, 16 were detected by RCA. Five missense mutations were detected by both methods in 18 of 23 (78% fluconazole-susceptible strains. DNA sequencing revealed that mutations in non-susceptible isolates were all due to homozygous nucleotide changes. With the exception of the mutations leading to amino acid substitution E266D, those in fluconazole-susceptible strains were heterozygous. Amino acid substitutions common to both sets of isolates were D116E, E266D, K128T, V437I and V488I. Substitutions unique to isolates with reduced fluconazole susceptibility were G464 S (n = 4 isolates, G448E (n = 3, G307S (n = 3, K143R (n = 3 and Y123H, S405F and R467K (each n = 1. DNA sequencing revealed a novel substitution, G450V, in one isolate. Conclusion The sensitive RCA

  12. AVALIAÇÃO DOS MÉTODOS DE ETEST E MICRODILUIÇÃO EM CALDO PARA O ESTUDO DA SUSCETIBILIDADE DO Sporothrix schenckii COM O ITRACONAZOL

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    Ana Raquel Mano Meinerz

    2010-06-01

    Full Text Available The frequent occurrence of resistant isolated fungi againstantifungal drugs stimulated advances in the antifungigram techniques,which were standardized by CLSI. However, the methods have been inefficient and impractical to be executed in clinical laboratories. Within this context, commercial techniques have been developed, being ETEST one of them. ETEST has proved to be easier to execute when compared to the techniques approved by the CLSI. This study used the ETEST and the microdilution method, performed according to CLSI, for determining the in vitro susceptibility of isolates of Sporothrix schenckii against itraconazole. The CLSI uses RPMI 1640 medium and the reading of MIC after the period of incubation of 72h at 35ºC. MIC was determined by the ETEST, being Sabouraud dextrose agar used as medium, and the reading performed after 72 hours of incubation at 35ºC. The variance analysis, analyzed by T-paired test, did not demonstrate statistical differences among the CIM values obtained by the microdilution technique in broth (MIC among 0.219 and 0.875 μg/mL and ETEST (MIC among 0.032 and 2.0 μg/mL. However, the correlation coefficient (R was negative, probably because ofthe small number of samples. These results show the necessity offurther studies to assess the application of ETEST to evaluate thesusceptibility of S. schenckii against the itraconazol.

  13. Induction of Mitochondrial Reactive Oxygen Species Production by Itraconazole, Terbinafine, and Amphotericin B as a Mode of Action against Aspergillus fumigatus.

    Science.gov (United States)

    Shekhova, Elena; Kniemeyer, Olaf; Brakhage, Axel A

    2017-11-01

    Drug resistance in fungal pathogens is of incredible importance to global health, yet the mechanisms of drug action remain only loosely defined. Antifungal compounds have been shown to trigger the intracellular accumulation of reactive oxygen species (ROS) in human-pathogenic yeasts, but the source of those ROS remained unknown. In the present study, we examined the role of endogenous ROS for the antifungal activity of the three different antifungal substances itraconazole, terbinafine, and amphotericin B, which all target the fungal cell membrane. All three antifungals had an impact on fungal redox homeostasis by causing increased intracellular ROS production. Interestingly, the elevated ROS levels induced by antifungals were abolished by inhibition of the mitochondrial respiratory complex I with rotenone. Further, evaluation of lipid peroxidation using the thiobarbituric acid assay revealed that rotenone pretreatment decreased ROS-induced lipid peroxidation during incubation of Aspergillus fumigatus with itraconazole and terbinafine. By applying the mitochondrion-specific lipid peroxidation probe MitoPerOx, we also confirmed that ROS are induced in mitochondria and subsequently cause significant oxidation of mitochondrial membrane in the presence of terbinafine and amphotericin B. To summarize, our study suggests that the induction of ROS production contributes to the ability of antifungal compounds to inhibit fungal growth. Moreover, mitochondrial complex I is the main source of deleterious ROS production in A. fumigatus challenged with antifungal compounds. Copyright © 2017 American Society for Microbiology.

  14. Failure of fluconazole in treating cutaneous leishmaniasis caused by Leishmania guyanensis in the Brazilian Amazon: An open, nonrandomized phase 2 trial.

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    Valeska Albuquerque Francesconi

    2018-02-01

    Full Text Available The treatment of Leishmaniasis caused by Leishmania (Viannia guyanensis is based on a weak strength of evidence from very few clinical trials and some case series reports. Current treatment guidelines recommend pentamidine isethionate or meglumine antimoniate (Glucantime as the first-line choices. Both are parenteral drugs with a low therapeutic indexes leading to a high risk of undesired effects. Imidazole derivatives interfere with the production of leishmanial ergosterol, an essential component of their membrane structure. One drug that has been studied in different clinical presentations of Leishmania is fluconazole, a hydrophilic bis-triazole, which is easily absorbed through the oral route with a low toxicity profile and is considered safe for children. This drug is readily available in poor countries with a reasonable cost making it a potential option for treating leishmaniasis.An adaptive nonrandomized clinical trial with sequential groups with dose escalation of oral fluconazole was designed to treat adult men with localized cutaneous leishmaniasis (LCL in Manaus, Brazil. Eligible participants were patients with LCL with confirmed Leishmania guyanensis infection.Twenty adult male patients were treated with 450 mg of fluconazole daily for 30 days. One patient (5% was cured within 30 days of treatment. Of the 19 failures (95%, 13 developed a worsening of ulcers and six evolved lymphatic spreading of the disease. Planned dose escalation was suspended after the disappointing failure rate during the first stage of the trial.Oral fluconazole, at the dose of 450mg per day, was not efficacious against LCL caused by Leishmania guyanensis in adult men.Brazilian Clinical Trial Registration (ReBec-RBR-8w292w; UTN number-1158-2421.

  15. Species distribution and in vitro fluconazole susceptibility of clinical Candida isolates in a Brazilian tertiary-care hospital over a 3-year period

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    Márcia Cristina Furlaneto

    2011-10-01

    Full Text Available INTRODUCTION: In this study, we aimed at identifying Candida isolates obtained from blood, urine, tracheal secretion, and nail/skin lesions from cases attended at the Hospital Universitário de Londrina over a 3-year period and at evaluating fluconazole susceptibilities of the isolates. METHODS: Candida isolates were identified by polymerase chain reaction (PCR using species-specific forward primers. The in vitro fluconazole susceptibility test was performed according to EUCAST-AFST reference procedure. RESULTS: Isolates were obtained from urine (53.4%, blood cultures (19.2%, tracheal secretion (17.8%, and nail/skin lesions (9.6%. When urine samples were considered, prevalence was similar in women (45.5% and in men (54.5% and was high in the age group >61 years than that in younger ones. For blood samples, prevalence was high in neonates (35% and advanced ages (22.5%. For nail and skin samples, prevalence was higher in women (71.4% than in men (28.6%. Candida albicans was the most frequently isolated in the hospital, but Candida species other than C. albicans accounted for 64% of isolates, including predominantly Candida tropicalis (33.2% and Candida parapsilosis (19.2%. The trend for non-albicans Candida as the predominant species was noted from all clinical specimens, except from urine samples. All Candida isolates were considered susceptible in vitro to fluconazole with the exception of isolates belonging to the intrinsically less-susceptible species C. glabrata. CONCLUSIONS: Non-albicans Candida species were more frequently isolated in the hospital. Fluconazole resistance was a rare finding in our study.

  16. Fluconazole-Pyridoxine Bis-Triazolium Compounds with Potent Activity against Pathogenic Bacteria and Fungi Including Their Biofilm-Embedded Forms

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    Marsel R. Garipov

    2017-01-01

    Full Text Available Two novel quaternary ammonium salts, bis-triazolium derivatives of fluconazole and pyridoxine, were synthesized by reaction of fluconazole with pyridoxine-based synthetic intermediates. The leading compound demonstrated pronounced antimycotic and antibacterial in vitro activity, comparable to or exceeding that of the reference antifungal (fluconazole, terbinafine and antibacterial/antiseptic (miramistin, benzalkonium chloride agents. In contrast to many antimicrobials, the leading compound was also active against biofilm-embedded staphylococci and Escherichia coli. While no biofilm structure destruction occurred, all compounds were able to diffuse into the matrix and reduce the number of colony-forming units by three orders of magnitude at 16 × MBC. The leading compound was significantly less toxic than miramistin and benzalkonium chloride and more toxic than the reference antifungal drugs. The obtained results make the described chemotype a promising starting point for the development of new broad-spectrum antimicrobial therapies with powerful effect on fungal and bacterial pathogens including their biofilm-embedded forms.

  17. In vitro anti-Candida activity of selective serotonin reuptake inhibitors against fluconazole-resistant strains and their activity against biofilm-forming isolates.

    Science.gov (United States)

    Costa Silva, Rose Anny; da Silva, Cecília Rocha; de Andrade Neto, João Batista; da Silva, Anderson Ramos; Campos, Rosana Sousa; Sampaio, Letícia Serpa; do Nascimento, Francisca Bruna Stefany Aires; da Silva Gaspar, Brenda; da Cruz Fonseca, Said Gonçalves; Josino, Maria Aparecida Alexandre; Grangeiro, Thalles Barbosa; Gaspar, Danielle Macedo; de Lucena, David Freitas; de Moraes, Manoel Odorico; Cavalcanti, Bruno Coêlho; Nobre Júnior, Hélio Vitoriano

    2017-06-01

    Recent research has shown broad antifungal activity of the classic antidepressants selective serotonin reuptake inhibitors (SSRIs). This fact, combined with the increased cross-resistance frequency of the genre Candida regarding the main treatment today, fluconazole, requires the development of novel therapeutic strategies. In that context, this study aimed to assess the antifungal potential of fluoxetine, sertraline, and paroxetine against fluconazole-resistant Candida spp. planktonic cells, as well as to assess the mechanism of action and the viability of biofilms treated with fluoxetine. After 24 h, the fluconazole-resistant Candida spp. strains showed minimum inhibitory concentration (MIC) in the ranges of 20-160 μg/mL for fluoxetine, 10-20 μg/mL for sertraline, and 10-100.8 μg/mL for paroxetine by the broth microdilution method (M27-A3). According to our data by flow cytometry, each of the SSRIs cause fungal death after damaging the plasma and mitochondrial membrane, which activates apoptotic signaling pathways and leads to dose-dependant cell viability loss. Regarding biofilm-forming isolates, the fluoxetine reduce mature biofilm of all the species tested. Therefore, it is concluded that SSRIs are capable of inhibit the growth in vitro of Candida spp., both in planktonic form, as biofilm, inducing cellular death by apoptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Fluconazole and amphotericin-B resistance are associated with increased catalase and superoxide dismutase activity in Candida albicans and Candida dubliniensis

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    Carlos Eduardo Blanco Linares

    2013-12-01

    Full Text Available Introduction Candida dubliniensis, a new species of Candida that has been recovered from several sites in healthy people, has been associated with recurrent episodes of oral candidiasis in AIDS and HIV-positive patients. This species is closely related to C. albicans. The enzymatic activity of C. dubliniensis in response to oxidative stress is of interest for the development of drugs to combat C. dubliniensis. Methods Fluconazole- and amphotericin B-resistant strains were generated as described by Fekete-Forgács et al. (2000. Superoxide dismutase (SOD and catalase assays were performed as described by McCord and Fridovich (1969 and Aebi (1984, respectively. Results We demonstrated that superoxide dismutase (SOD and catalase activities were significantly higher (p<0.05 in the fluconazole- and amphotericin B-resistant strains of C. dubliniensis and C. albicans than in the sensitive strains. The catalase and SOD activities were also significantly (p<0.01 higher in the sensitive and resistant C. albicans strains than in the respective C. dubliniensis strains. Conclusions These data suggest that C. albicans is better protected from oxidative stress than C. dubliniensis and that fluconazole, like amphotericin B, can induce oxidative stress in Candida; oxidative stress induces an adaptive response that results in a coordinated increase in catalase and SOD activities.

  19. Standardization of a fluconazole bioassay and correlation of results with those obtained by high-pressure liquid chromatography.

    Science.gov (United States)

    Rex, J H; Hanson, L H; Amantea, M A; Stevens, D A; Bennett, J E

    1991-01-01

    An improved bioassay for fluconazole was developed. This assay is sensitive in the clinically relevant range (2 to 40 micrograms/ml) and analyzes plasma, serum, and cerebrospinal fluid specimens; bioassay results correlate with results obtained by high-pressure liquid chromatography (HPLC). Bioassay and HPLC analyses of spiked plasma, serum, and cerebrospinal fluid samples (run as unknowns) gave good agreement with expected values. Analysis of specimens from patients gave equivalent results by both HPLC and bioassay. HPLC had a lower within-run coefficient of variation (less than 2.5% for HPLC versus less than 11% for bioassay) and a lower between-run coefficient of variation (less than 5% versus less than 12% for bioassay) and was more sensitive (lower limit of detection, 0.1 micrograms/ml [versus 2 micrograms/ml for bioassay]). The bioassay is, however, sufficiently accurate and sensitive for clinical specimens, and its relative simplicity, low sample volume requirement, and low equipment cost should make it the technique of choice for analysis of routine clinical specimens. PMID:1854166

  20. Genome-wide expression profiling of the response to short-term exposure to fluconazole in Cryptococcus neoformans serotype A

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    Sanguinetti Maurizio

    2011-05-01

    Full Text Available Abstract Background Fluconazole (FLC, a triazole antifungal drug, is widely used for the maintenance therapy of cryptococcal meningoencephalitis, the most common opportunistic infection in AIDS patients. In this study, we examined changes in the gene expression profile of the C. neoformans reference strain H99 (serotype A following FLC treatment in order to investigate the adaptive cellular responses to drug stress. Results Simultaneous analysis of over 6823 transcripts revealed that 476 genes were responsive to FLC. As expected up-regulation of genes involved in ergosterol biosynthesis was observed, including the azole target gene ERG11 and ERG13, ERG1, ERG7, ERG25, ERG2, ERG3 and ERG5. In addition, SRE1 which is a gene encoding a well-known regulator of sterol homeostasis in C. neoformans was up-regulated. Several other genes such as those involved in a variety of important cellular processes (i.e. lipid and fatty acid metabolism, cell wall maintenance, stress and virulence were found to be up-regulated in response to FLC treatment. Conversely, expression of AFR1, the major transporter of azoles in C. neoformans, was not regulated by FLC. Conclusions Short-term exposure of C. neoformans to FLC resulted in a complex altered gene expression profile. Some of the observed changes could represent specific adaptive responses to the antifungal agent in this pathogenic yeast.

  1. Impact of Resistance to Fluconazole on Virulence and Morphological Aspects of Cryptococcus neoformans and Cryptococcus gattii Isolates.

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    Suélen Andreia eRossi

    2016-02-01

    Full Text Available Cryptococcus spp. are responsible for around one million cases of meningitis every year. Fluconazole (FLU is commonly used in the treatment of cryptococcosis, mainly in immunocompromised patients and the resistance is usually reported after long periods of treatment. In this study, the morphological characterization and virulence profile of FLU-susceptible and FLU-resistant clinical and environmental isolates of C. neoformans and C. gattii were performed both in vitro and in vivo using the Galleria mellonella model. FLU-susceptible isolates from C. neoformans were significantly more virulent than the FLU-resistant isolates. FLU-susceptible C. gattii isolates showed a different virulence profile from C. neoformans isolates where only the environmental isolate, CL, was more virulent compared with the resistant isolates. Cell morphology and capsule size were analyzed and the FLU-resistant isolates did not change significantly compared with the most sensitive isolates. Growth at 37°C was also evaluated and in both species, the resistant isolates showed a reduced growth at this temperature, indicating that FLU resistance can affect their growth. Based on the results obtained is possible suggest that FLU resistance can influence the morphology of the isolates and consequently changed the virulence profiles. The most evident results were observed for C. neoformans showing that the adaptation of isolates to antifungal selective pressure influenced the loss of virulence.

  2. Fluconazole affects the alkali-metal-cation homeostasis and susceptibility to cationic toxic compounds of Candida glabrata.

    Science.gov (United States)

    Elicharova, Hana; Sychrova, Hana

    2014-08-01

    Candida glabrata is a salt-tolerant and fluconazole (FLC)-resistant yeast species. Here, we analyse the contribution of plasma-membrane alkali-metal-cation exporters, a cation/proton antiporter and a cation ATPase to cation homeostasis and the maintenance of membrane potential (ΔΨ). Using a series of single and double mutants lacking CNH1 and/or ENA1 genes we show that the inability to export potassium and toxic alkali-metal cations leads to a slight hyperpolarization of the plasma membrane of C. glabrata cells; this hyperpolarization drives more cations into the cells and affects cation homeostasis. Surprisingly, a much higher hyperpolarization of C. glabrata plasma membrane was produced by incubating cells with subinhibitory concentrations of FLC. FLC treatment resulted in a substantially increased sensitivity of cells to various cationic drugs and toxic cations that are driven into the cell by negative-inside plasma-membrane potential. The effect of the combination of FLC plus cationic drug treatment was enhanced by the malfunction of alkali-metal-cation transporters that contribute to the regulation of membrane potential and cation homeostasis. In summary, we show that the combination of subinhibitory concentrations of FLC and cationic drugs strongly affects the growth of C. glabrata cells. © 2014 The Authors.

  3. Simultaneous determination of benznidazole and itraconazole using spectrophotometry applied to the analysis of mixture: A tool for quality control in the development of formulations.

    Science.gov (United States)

    Pinho, Ludmila A G; Sá-Barreto, Lívia C L; Infante, Carlos M C; Cunha-Filho, Marcílio S S

    2016-04-15

    The aim of this work was the development of an analytical procedure using spectrophotometry for simultaneous determination of benznidazole (BNZ) and itraconazole (ITZ) in a medicine used for the treatment of Chagas disease. In order to achieve this goal, the analysis of mixtures was performed applying the Lambert-Beer law through the absorbances of BNZ and ITZ in the wavelengths 259 and 321 nm, respectively. Diverse tests were carried out for development and validation of the method, which proved to be selective, robust, linear, and precise. The lower limits of detection and quantification demonstrate its sensitivity to quantify small amounts of analytes, enabling its application for various analytical purposes, such as dissolution test and routine assays. In short, the quantification of BNZ and ITZ by analysis of mixtures had shown to be efficient and cost-effective alternative for determination of these drugs in a pharmaceutical dosage form. Copyright © 2016. Published by Elsevier B.V.

  4. In Vitro Activity of Posaconazole against Talaromyces marneffei by Broth Microdilution and Etest Methods and Comparison to Itraconazole, Voriconazole, and Anidulafungin

    OpenAIRE

    Lau, Susanna K. P.; Lo, George C. S.; Lam, Clare S. K.; Chow, Wang-Ngai; Ngan, Antonio H. Y.; Wu, Alan K. L.; Tsang, Dominic N. C.; Tse, Cindy W. S.; Que, Tak-Lun; Tang, Bone S. F.; Woo, Patrick C. Y.

    2017-01-01

    We determined the susceptibilities of 57 Talaromyces marneffei strains to anidulafungin, itraconazole, voriconazole, and posaconazole with MICs of 2 to 8, 0.002 to 0.004, 0.016 to 0.063, and 0.001 to 0.002 μg/ml by broth microdilution and >32, ≤0.002 to 0.008, ≤0.002 to 0.008, and ≤0.002 μg/ml by Etest, respectively, at yeast phase; MICs at mycelial phase for anidulafungin and posaconazole were 1 to 2 and 0.004 to 0.063 μg/ml, respectively. The results suggest promising activities of posacona...

  5. Simultaneous determination of benznidazole and itraconazole using spectrophotometry applied to the analysis of mixture: A tool for quality control in the development of formulations

    Science.gov (United States)

    Pinho, Ludmila A. G.; Sá-Barreto, Lívia C. L.; Infante, Carlos M. C.; Cunha-Filho, Marcílio S. S.

    2016-04-01

    The aim of this work was the development of an analytical procedure using spectrophotometry for simultaneous determination of benznidazole (BNZ) and itraconazole (ITZ) in a medicine used for the treatment of Chagas disease. In order to achieve this goal, the analysis of mixtures was performed applying the Lambert-Beer law through the absorbances of BNZ and ITZ in the wavelengths 259 and 321 nm, respectively. Diverse tests were carried out for development and validation of the method, which proved to be selective, robust, linear, and precise. The lower limits of detection and quantification demonstrate its sensitivity to quantify small amounts of analytes, enabling its application for various analytical purposes, such as dissolution test and routine assays. In short, the quantification of BNZ and ITZ by analysis of mixtures had shown to be efficient and cost-effective alternative for determination of these drugs in a pharmaceutical dosage form.

  6. Susceptibility testing of terbinafine alone and in combination with amphotericin B, itraconazole, or voriconazole against conidia and hyphae of dematiaceous molds.

    Science.gov (United States)

    Biancalana, Fernanda Simas Corrêa; Lyra, Luzia; Moretti, Maria Luiza; Schreiber, Angélica Zaninelli

    2011-12-01

    Studies have demonstrated excellent in vivo efficacy of terbinafine combined with other antifungal agents against dematiaceous molds; however, there is a lack of in vitro studies. Most studies evaluated conidia inocula, but susceptibility testing of hyphae could mimic the fungal status in infected tissues and might reflect the therapeutic potential of the agent. We investigated the in vitro susceptibility of terbinafine alone and in combination with amphotericin B, itraconazole, or voriconazole against conidia by microdilution and dynamic measurement of hyphae growth of dematiaceous molds. The MIC values for hyphae were, until 3 dilutions, below the MIC obtained for conidia. The results indicated 100% synergistic interactions between terbinafine and azoles or amphotericin B in all tests, but lower MICs for hyphae. In conclusion, our findings allow us to say that the hyphal form of tested dematiaceous molds showed high susceptibility to all antifungal agents evaluated, alone and in combination with terbinafine. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Multicenter evaluation of MIC distributions for epidemiologic cutoff value definition to detect amphotericin B, posaconazole, and itraconazole resistance among the most clinically relevant species of Mucorales.

    Science.gov (United States)

    Espinel-Ingroff, A; Chakrabarti, A; Chowdhary, A; Cordoba, S; Dannaoui, E; Dufresne, P; Fothergill, A; Ghannoum, M; Gonzalez, G M; Guarro, J; Kidd, S; Lass-Flörl, C; Meis, J F; Pelaez, T; Tortorano, A M; Turnidge, J

    2015-03-01

    Clinical breakpoints (CBPs) have not been established for the Mucorales and any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and four Mucorales species. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces variabilis, 32 Cunninghamella bertholletiae, 136 Lichtheimia corymbifera, 10 Mucor indicus, 123 M. circinelloides, 19 M. ramosissimus, 349 Rhizopus arrhizus, 146 R. microsporus, 33 Rhizomucor pusillus, and 36 Syncephalastrum racemosum isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: amphotericin B ECVs for L. corymbifera were 1 and 2 μg/ml, those for M. circinelloides were 1 and 2 μg/ml, those for R. arrhizus were 2 and 4 μg/ml, and those for R. microsporus were 2 and 2 μg/ml, respectively; posaconazole ECVs for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2, respectively; both itraconazole ECVs for R. arrhizus were 2 μg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Determination of fluconazole in serum and amniotic fluid of rats by gas-chromatography/mass spectometry (GC/MS Determinação de fluconazol em soro e líquido amniótico de ratas por cromatografia a gas/espectrometria de massas (CG/EM

    Directory of Open Access Journals (Sweden)

    Dione Marçal Lima

    2005-06-01

    Full Text Available Rats treated with oral dose of 100 mg/kg of fluconazole during pregnancy had their serum and amniotic fluid quantified for this drug using a GC/MS method. Fluconazole was extracted with ethyl acetate from samples and analysed by a GC-MS Shimadzu QP5050A system using a CBP-5 fused silica capillary column. Tioconazole was used as internal standard. Calibration curve was linear within the range 10.0 - 300.0 µg/mL. The limit of quantification was 0.1 µg/mL and no interference was observed in the blank serum and amniotic liquid. The mean concentrations of the drug in the serum and amniotic fluid were 206.01 ± 105.25 µg/mL and 125.34 ± 65.24 mug/mL, respectively. This procedure showed to be sensitive and efficient enough for the use in teratogenic studies of fluconazole and other azole drugs.Soro e líquido amniótico de ratas tratadas com fluconazol (dose oral de 100 mg/kg durante a prenhez foram quantificados para este fármaco usando cromatografia gasosa acoplada à espectroscopia de massas (CG/EM. O fluconazol foi extraído das amostras com acetato de etila e analisado empregando-se um cromatógrafo CG/EM Shimadzu QP5050A com coluna capilar de sílica fundida CBP-5. O tioconazol foi utilizado como padrão interno. A curva padrão foi linear no intervalo das concentrações de 10,0 a 300,0 µg/mL. O limite de quantificação foi de 0,1 µg/mL e não foi observada interferência no branco de soro e líquido amniótico. As concentrações médias do fármaco no soro e líquido amniótico foram 206,01 ± 105,25 µg/mL e 125,34 ± 65,24 µg/mL, respectivamente. Este procedimento mostrou-se sensível e eficiente para ser usado em estudos de teratogenicidade do fluconazol e outros azóis.

  9. Validation of high-performance liquid chromatographic method for analysis of fluconazole in microemulsions and liquid crystals

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    Hilris Rocha e Silva

    2014-04-01

    Full Text Available In recent decades, there has been a significant increase in the incidence of fungal diseases. Certain fungal diseases cause cutaneous lesions and in the usual treatment, generally administred orally, the drug reaches the site of action with difficulty and its concentration is too low. An approach much explored in recent years is the development of nanotechnology-based drug delivery systems, and microemulsions (ME and liquid crystals (LC are promising. ME and LC were developed with oleic acid or copaiba oil as the oil phase, propoxyl (5OP ethoxyl (20 OE cetyl alcohol as surfactant and water. An analytical method to assess the incorporation of fluconazole (FLU in the systems under study was validated according to guidelines of the International Conference on Harmonization (ICH guidelines and the Brazilian Food, Drug and Sanitation Agency (ANVISA. The method was conducted on a C18-RP column (250 × 4.6 mm i.d., maintained at room temperature. The mobile phase consisted of acetonitrile and water (50:50, v/v, run at a flow rate of 1.0mL/min and using ultraviolet detection at 210nm. The chromatographic separation was obtained with a retention time of 6.3min, and was linear in the range of 20-400 µg/mL (r2=0.9999. The specificity showed no interference of the excipients. The accuracy was 100.76%. The limits of detection and quantitation were 0.057 and 0.172 µg.mL-1, respectively. Moreover, method validation demonstrated satisfactory results for precision and robustness. The proposed method was applied for the analysis of the incorporation of FLU in ME and LC, contributing to improve the quality control and to assure the therapeutic efficacy.

  10. Micellar HPLC and derivative spectrophotometric methods for the simultaneous determination of fluconazole and tinidazole in pharmaceuticals and biological fluids.

    Science.gov (United States)

    Belal, F; Sharaf El-Din, M K; Eid, M I; El-Gamal, R M

    2014-04-01

    Micellar high-performance liquid chromatography (HPLC) and first-derivative ultraviolet spectrophotometry were used to simultaneously determine fluconazole (FLZ) and tinidazole (TNZ) in combined pharmaceutical dosage forms. The derivative procedure is based on the linear relationship between the drug concentration and the first derivative amplitudes at 220 and 288 nm for FLZ and TNZ, respectively. The calibration graphs were linear in the range of 1.5-9.0 µg/mL for FLZ and 10.0-60.0 µg/mL for TNZ. Furthermore, an HPLC procedure with ultraviolet detection at 210 nm was developed. For the HPLC procedure, good chromatographic separation was achieved using an ODS C18 column (250 × 4.6 mm i.d.). The mobile phase containing 0.15M sodium dodecyl sulphate, 0.3% triethylamine and 12% n-propanol in 0.02M orthophosphoric acid at pH 5.5 was pumped at a flow rate of 1 mL/min. Indapamide was used as an internal standard. The method showed good linearity over the concentration ranges of 1.5-30.0 and 10.0-200.0 µg/mL, with limits of detection of 0.36 and 2.70 µg/mL and limits of quantification of 1.1 and 8.2 µg/mL for FLZ and TNZ, respectively. The suggested methods were successfully applied for the simultaneous analysis of the drugs in their laboratory prepared mixture, co-formulated tablet and single dosage forms. Moreover the second method was also extended to the determination of the drugs in biological fluids.

  11. Regression analysis and categorical agreement of fluconazole disk zone diameters and minimum inhibitory concentration by broth microdilution of clinical isolates of Candida.

    Science.gov (United States)

    Aggarwal, P; Kashyap, B

    2017-06-01

    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. 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. 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≤0.25-64μg/ml while that of Candida glabrata ranged from≤0.25-128μg/ml. Categorical agreement between disk diffusion and broth microdilution was 86.8%. Pearson's coefficient of correlation was -0.5975 indicating moderate negative correlation between the two variables. Zone sizes can be used to estimate the MIC values, although with limited accuracy. There should be a constant effort to upgrade the guidelines in view of new clinical data, and laboratories should make an active effort to incorporate them. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. In Vitro Dissolution of Fluconazole and Dipyridamole in Gastrointestinal Simulator (GIS), Predicting in Vivo Dissolution and Drug-Drug Interaction Caused by Acid-Reducing Agents.

    Science.gov (United States)

    Matsui, Kazuki; Tsume, Yasuhiro; Amidon, Gregory E; Amidon, Gordon L

    2015-07-06

    Weakly basic drugs typically exhibit pH-dependent solubility in the physiological pH range, displaying supersaturation or precipitation along the gastrointestinal tract. Additionally, their oral bioavailabilities may be affected by coadministration of acid-reducing agents that elevate gastric pH. The purpose of this study was to assess the feasibility of a multicompartmental in vitro dissolution apparatus, Gastrointestinal Simulator (GIS), in predicting in vivo dissolution of certain oral medications. In vitro dissolution studies of fluconazole, a BCS class I, and dipyridamole, a BCS class II weak bases (class IIb), were performed in the GIS as well as United States Pharmacopeia (USP) apparatus II and compared with the results of clinical drug-drug interaction (DDI) studies. In both USP apparatus II and GIS, fluconazole completely dissolved within 60 min regardless of pH, reflecting no DDI between fluconazole and acid-reducing agents in a clinical study. On the other hand, seven-fold and 15-fold higher concentrations of dipyridamole than saturation solubility were observed in the intestinal compartments in GIS with gastric pH 2.0. Precipitation of dipyridamole was also observed in the GIS, and the percentage of dipyridamole in solution was 45.2 ± 7.0%. In GIS with gastric pH 6.0, mimicking the coadministration of acid-reducing agents, the concentration of dipyridamole was equal to its saturation solubility, and the percentage of drug in solution was 9.3 ± 2.7%. These results are consistent with the clinical DDI study of dipyridamole with famotidine, which significantly reduced the Cmax and area under the curve. An In situ mouse infusion study combined with GIS revealed that high concentration of dipyridamole in the GIS enhanced oral drug absorption, which confirmed the supersaturation of dipyridamole. In conclusion, GIS was shown to be a useful apparatus to predict in vivo dissolution for BCS class IIb drugs.

  13. (Gynazole-1® Compared to Fluconazole 150 mg Tablets (Diflucan® in the Time to Relief of Symptoms in Patients With Vulvovaginal Candidiasis

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    Larry S. Seidman

    2005-01-01

    Full Text Available Background. It is estimated that as many as 13 million cases of vulvovaginal infection occur in the United States annually, the majority of which are the result of Candida albicans infection. The symptoms of vulvovaginal infections are often painful and distressing to the patient. The objective of this study was to compare the time to symptomatic relief of vulvovaginal candidiasis (VVC with butoconazole nitrate 2% Site Release® vaginal cream (Gynazole-1® and oral fluconazole 150 mg tablets (Diflucan®.

  14. Comparative effectiveness of echinocandins versus fluconazole therapy for the treatment of adult candidaemia due to Candida parapsilosis: a retrospective observational cohort study of the Mycoses Study Group (MSG-12).

    Science.gov (United States)

    Chiotos, Kathleen; Vendetti, Neika; Zaoutis, Theoklis E; Baddley, John; Ostrosky-Zeichner, Luis; Pappas, Peter; Fisher, Brian T

    2016-12-01

    A polymorphism in the gene encoding β-1,3-glucan synthase, the target of the echinocandin class of antifungals, results in increased in vitro MICs of the echinocandins. This has resulted in controversy surrounding use of the echinocandins for treatment of Candida parapsilosis candidaemia. We aimed to compare 30 day mortality in adults with C. parapsilosis candidaemia treated with echinocandins versus fluconazole. This is a retrospective observational cohort study. We used the Premier Perspective Database to identify adult patients with C. parapsilosis candidaemia treated with only fluconazole or only an echinocandin as definitive therapy. The primary outcome was 30 day mortality. Propensity scores were derived to estimate the probability the patient would have received either an echinocandin or fluconazole. Inverse probability of treatment weighting (IPTW) was used in a weighted logistic regression to calculate odds of 30 day mortality. There were 307 unique patients with C. parapsilosis candidaemia. One hundred and twenty-six (41%) received fluconazole and 181 (59%) received an echinocandin. Age, gender, race, year of admission, need for ICU resources in the week prior to candidaemia onset, and receipt of vasopressors on the day of candidaemia onset were included in the propensity score model used to calculate inverse probability of treatment weights. Weighted logistic regression demonstrated no difference in 30 day mortality between patients receiving an echinocandin as compared with fluconazole (OR 0.82, 95% CI 0.33-2.07). Our result supports the 2016 IDSA invasive candidiasis guidelines, which no longer clearly favour treatment with fluconazole over an echinocandin for C. parapsilosis candidaemia. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Thermo-acoustical analysis of sodium dodecyl sulfate: Fluconazole (antifungal drug) based micellar system in hydro-ethanol solutions for potential drug topical application

    International Nuclear Information System (INIS)

    Bhardwaj, Tarun; Bhardwaj, Varun; Sharma, Kundan; Gupta, Abhishek; Cameotra, Swaranjit Singh; Sharma, Poonam

    2014-01-01

    Highlights: • The mixed micellar system was analyzed for sodium dodecyl sulfate and fluconazole. • Early micellization was found with CMC shift towards lower surfactant concentration. • Negative ΔG m o values suggested that the micelle formation is spontaneous and feasible. • Thermo-acoustical parameters revealed the existence of intermolecular interactions within the molecules. - Abstract: Micellar systems hold excellent drug delivery applications due to their capability to solubilize a large number of hydrophobic and hydrophilic molecules. In this present work, the mixed micelle formation between the anionic surfactant sodium dodecyl sulfate (SDS) and the ‘Azole’ derivative antifungal drug fluconazole (FLZ) have been studied at four temperatures in different hydro-ethanolic solutions. The critical micelle concentration (CMC) was determined by specific conductance techniques and the experimental data was used to calculate several useful thermodynamic parameters, like standard free energy, enthalpy and entropy of micelle formation. Early micellization was found with critical micelle concentration shifting towards lower concentration (CMC) than the standard concentration of SDS in water at 25 °C suggesting that drug and the solvent system facilitates the micellization process. In addition, the transport properties were examined by employing controlled approaches likely, apparent molar volume (ϕ v ), apparent molar adiabatic compression (ϕ k ), and isentropic compression (κ s ) of SDS in presence of FLZ. These parameters revealed the existence of intermolecular interactions within the molecules. Therefore, this study would cast light on utilizing surfactant immobilized FLZ system for better topical biological action

  16. Synergism Effect of the Essential Oil from Ocimum basilicum var. Maria Bonita and Its Major Components with Fluconazole and Its Influence on Ergosterol Biosynthesis

    Science.gov (United States)

    Cardoso, Nathalia N. R.; Alviano, Celuta S.; Blank, Arie F.; Romanos, Maria Teresa V.; Fonseca, Beatriz B.; Rozental, Sonia; Rodrigues, Igor A.; Alviano, Daniela S.

    2016-01-01

    The aim of this study was to evaluate the activity of the EO and its major components of Ocimum basilicum var. Maria Bonita, a genetically improved cultivar, against the fluconazole sensitive and resistant strains of Candida albicans and Cryptococcus neoformans. Geraniol presented better results than the EO, with a low MIC (76 μg/mL against C. neoformans and 152 μg/mL against both Candida strains). The combination of EO, linalool, or geraniol with fluconazole enhanced their antifungal activity, especially against the resistant strain (MIC reduced to 156, 197, and 38 μg/mL, resp.). The ergosterol assay showed that subinhibitory concentrations of the substances were able to reduce the amount of sterol extracted. The substances tested were able to reduce the capsule size which suggests they have an important mechanism of action. Transmission electron microscopy demonstrated cell wall destruction of C. neoformans after treatment with subinhibitory concentrations. In C. albicans ultrastructure alterations such as irregularities in the membrane, presence of vesicles, and cell wall thickening were observed. The biofilm formation was inhibited in both C. albicans strains at MIC and twice MIC. These results provide further support for the use of O. basilicum EO and its major components as a potential source of antifungal agents. PMID:27274752

  17. Role of fluconazole in the long-term suppressive therapy of fungal infections in patients with artificial implants.

    Science.gov (United States)

    Penk, A; Pittrow, L

    1999-12-01

    With the increased use of artificial implants the management of related infections has become an important challenge. Normally an infected implant would be removed. In many cases this might be contraindicated and drug treatment remains as the only alternative. As microbiological eradication is often impossible, especially in fungal infections at artificial implants (FIAI) long-term suppressive therapy might be required. The objective of this study was to determine the therapeutic value of fluconazole (F) in the management of FIAI. Clinical data of 56 patients (pts) with proven or suspected fungal infections and artificial implants (FIAI) subsequently treated with F were analyzed retrospectively. FIAI caused by species with intrinsic resistance to F have been excluded from the study. The following implants were involved: prosthetic valve endocarditis (PVE) 25 pts (44.6%), intraocular lenses (IL) 9 pts (16.1%), ventriculoperitoneal shunts (VPS) 6 pts (10.7%), knee prostheses (KP) 5 pts (8.9%), biliary stents (BS) 4 pts (7.1 %), venous access devices (VAS) 3 pts (5.4%), urinary stents (US) 2 pts (3.6%), breast implant and pacemaker 1 patient (1.8%) each. Underlying diseases were valve insufficiency (in PVE), cataract surgery (in IL), prematurity in newborns (in VPS), arthrosis (in KP), biliary obstruction (in BS), cystic fibrosis (in VAS), and obstructive renal calculi (in US). Candida species (C. spp.) were the most frequently detected causative agents with C. parapsilosis as the leading cause (n = 19; 33.9%). Furthermore C. albicans (n = 15; 26.8%), C. spp. and fungi not further specified (n = 8; 14.3%), C. tropicalis (n = 3; 5.4%), C. glabrata (n = 3; 5.4%), and C. lusitaniae (n = 1; 1.8%) were identified. Acremonium kiliense has been detected in 4 pts (7.1%), Cryptococcus neoformans in 2 pts (3.6 %). Histoplasma capsulatum was identified in 1 patient (1.8%). The maximum duration of treatment with F was lifelong with a maximum recorded duration of 4,5 years. The

  18. Fungicidal efficacy of various honeys against fluconazole-resistant Candida species isolated from HIV+ patients with candidiasis.

    Science.gov (United States)

    Shokri, H; Sharifzadeh, A

    2017-06-01

    Honey is well known to possess a broad spectrum of activity against medically important organisms. The purpose of this study was to assess the antifungal activity of different honeys against 40 fluconazole (FLU) resistant Candida species, including Candida albicans (C. albicans), Candida glabrata, Candida krusei and Candida tropicalis. Three honey samples were collected from northern (Mazandaran, A), southern (Hormozgan, B) and central (Lorestan, C) regions of Iran. A microdilution technique based on the CLSI, M27-A2 protocol was employed to compare the susceptibility of honeys "A", "B" and "C" against different pathogenic Candida isolates. The results showed that different Candida isolates were resistant to FLU, ranging from 64μg/mL to 512μg/mL. All of the honeys tested had antifungal activities against FLU-resistant Candida species, ranging from 20% to 56.25% (v/v) and 25% to 56.25% (v/v) for minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs), respectively. Honey "A" (MIC: 31.59%, v/v) showed higher anti-Candida activity than honey "B" (MIC: 35.99%, v/v) and honey "C" (MIC: 39.2%, v/v). No statistically significant differences were observed among the mean MIC values of the honey samples (P>0.05). The order of overall susceptibility of Candida species to honey samples were; C. krusei>C. glabrata>C. tropicalis>C. albicans (P>0.05). In addition, the mean MICs of Candida strains isolated from the nail, vagina and oral cavity were 33.68%, 36.44% and 39.89%, respectively, and were not significantly different (P>0.05). Overall, varying susceptibilities to the anti-Candida properties of different honeys were observed with four FLU-resistant species of Candida. Further research is needed to assess the efficacy of honey as an inhibitor of candidal growth in clinical trials. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide.

    Science.gov (United States)

    Kast, Richard E; Karpel-Massler, Georg; Halatsch, Marc-Eric

    2014-09-30

    CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective. Although esthetically unpleasing to use so many drugs at once, the closely similar drugs of the original CUSP9 used together have been well-tolerated when given on a compassionate-use basis in the cases that have come to our attention so far. We expect similarly good tolerability for CUSP9*. The combined action of this suite of drugs blocks signaling at, or the activity of, AKT phosphorylation, aldehyde dehydrogenase, angiotensin converting enzyme, carbonic anhydrase -2,- 9, -12, cyclooxygenase-1 and -2, cathepsin B, Hedgehog, interleukin-6, 5-lipoxygenase, matrix metalloproteinase -2 and -9, mammalian target of rapamycin, neurokinin-1, p-gp efflux pump, thioredoxin reductase, tissue factor, 20 kDa translationally controlled tumor protein, and vascular endothelial growth factor. We believe that given the current prognosis after a glioblastoma has recurred, a trial of CUSP9* is warranted.

  20. Enhanced transmucosal delivery of itraconazole by thiolated d-ɑ-tocopheryl poly(ethylene glycol) 1000 succinate micelles for the treatment of Candida albicans.

    Science.gov (United States)

    Suksiriworapong, Jiraphong; Mingkwan, Thawanrat; Chantasart, Doungdaw

    2017-11-01

    This study aimed to investigate the transmucosal delivery of itraconazole (ITZ) by thiolated d-ɑ-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS-Cys) micelles. TPGS-Cys polymer was successfully synthesized by the simple coupling between carboxyl-activated TPGS and Cys as confirmed by NMR and FTIR techniques. Afterwards, the TPGS/TPGS-Cys micelles were prepared using the blend of TPGS and TPGS-Cys at 10:0, 7:3, 5:5, 3:7 and 0:10mass ratios. All micelles had the size ranged from 8 to 10nm with narrow size distribution and showed spherical in shape. The surface of the 10:0 TPGS micelles exhibited negatively charge while, the TPGS-Cys micelles demonstrated the slightly positive surface charge. The critical micelle concentration, loading capacity and release profiles of TPGS/TPGS-Cys micelles were comparable to the TPGS micelles. The release of ITZ from all micelles was biphasic and sustained in simulated saliva fluid over 48h. The 3:7 and 0:10 TPGS/TPGS-Cys micelles had a good mucoadhesive property. Meanwhile, only 0:10 TPGS/TPGS-Cys micelles enhanced the permeability through buccal mucosa and potentiated the antifungal activity of ITZ against Candida albicans by at least 1.35 folds as compared to ITZ alone. Therefore, this formulation can be further developed for the transmucosal delivery of ITZ for the treatment of C. albicans. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Formulation and characterization of biocompatible and stable I.V. itraconazole nanosuspensions stabilized by a new stabilizer polyethylene glycol-poly(β-Benzyl-l-aspartate) (PEG-PBLA).

    Science.gov (United States)

    Zong, Lanlan; Li, Xiaohua; Wang, Haiyan; Cao, Yanping; Yin, Li; Li, Mengmeng; Wei, Zhihao; Chen, Dongxiao; Pu, Xiaohui; Han, Jihong

    2017-10-05

    Amphiphilic block copolymers, PEG-PBLA with different molecular weights, were synthesized and used as new stabilizers for Itraconazole nannosuspensions (ITZ-PBLA-Nanos). ITZ-PBLA-Nanos were prepared by the microprecipitation-high pressure homogenization method, and the particle size and zeta potential were measured using a ZetaSizer Nano-ZS90. Morphology and crystallinity were studied using TEM, DSC and powder X-ray. The effect of the PEG-to-PBLA ratio, and the drug-to-stabilizer ratio were investigated to obtain the optimal formulation. It was found that the optimal length of hydrophobic block was 25 BLA-NCA molecules and the optimal ratio of drug/stabilizer was 1:1, where the resulted average particle size of ITZ-PBLA-Nanos was 262.1±7.13nm with a PDI value of 0.163±0.011. The images of TEM suggest that ITZ-PBLA-Nanos were rectangular in shape. ITZ existed as crystals in the nanoparticles as suggested by the DSC and XRD results. Compared with the crude drug suspensions, the dissolution rate of ITZ nanocrystals, was significantly increased and was similar to Sporanox ® injection. The ITZ-PBLA-Nanos also demonstrated better dilution stability and storage stability compared with ITZ-F68-Nanos. The particle size of ITZ-PBLA-Nanos did not change significantly after incubated in rat plasma for 24h which is a good attribute for I.V. administration. Acute toxicity tests showed that ITZ-PBLA-Nanos has the highest LD 50 compared with ITZ-F68-Nanos and Sporanox ® injection. ITZ-PBLA-Nanos also showed stronger inhibiting effect on the growth of Candida albicans compared with Sporanox ® injection. Therefore, PEG-PBLA has a promising potential as a biocompatible stabilizer for ITZ nanosuspensions and potentially for other nanosuspensions as well. Copyright © 2017. Published by Elsevier B.V.

  2. ACTIVIDAD ANTIMICÓTICA DEL ACEITE ESENCIAL DE LAS HOJAS DE Minthostachys mollis (MUÑA) COMPARADO CON EL FLUCONAZOL EN CULTIVO DE Candida albicans

    OpenAIRE

    Katherine M Alcalá-Marcos; A. Giancarlo Alvarado-Gamarra; L Arturo Alejandro-Paredes; Eduardo Huayané-Linares

    2011-01-01

    Objetivo.- Demostrar el efecto antimicótico del aceite esencial de las hojas de Minthostachys mollis (muña) en comparación con el Fluconazol en cultivo de Candida albicans. Materiales y Método.- Estudio experimental. El efecto antimicótico se estudió midiendo 80 halos de inhibición distribuidos en 5 grupos mediante el método Kirby-Bauer. Se utilizó una cepa clínica de Candida albicans. Los grupos de estudio fueron grupo muña 25% (GM25%), grupo muña 50% (GM50%), grupo muña 100% (GM100%), un g...

  3. Primary Cutaneous Cryptococcosis Treated with Debridement and Fluconazole Monotherapy in an Immunosuppressed Patient: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jennifer Wang

    2015-01-01

    Full Text Available Cryptococcus neoformans is an opportunistic yeast present in the environment. Practitioners are familiar with the presentation and management of the most common manifestation of cryptococcal infection, meningoencephalitis, in patients with AIDS or other conditions of immunocompromise. There is less awareness, however, of uncommon presentations where experience rather than evidence guides therapy. We report a case of primary cutaneous cryptococcosis (PCC in a patient who had been immunosuppressed by chronic high-dose corticosteroid for the treatment of severe asthma. This case highlights the importance of early recognition of aggressive cellulitis that fails standard empiric antibiotic treatment in an immunocompromised patient. It also demonstrates successful treatment of PCC with a multispecialty approach including local debridement and fluconazole monotherapy.

  4. Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans.

    Science.gov (United States)

    Petraitis, Vidmantas; Petraitiene, Ruta; Kelaher, Amy M; Sarafandi, Alia A; Sein, Tin; Mickiene, Diana; Bacher, John; Groll, Andreas H; Walsh, Thomas J

    2004-10-01

    PLD-118, formerly BAY 10-8888, is a synthetic antifungal derivative of the naturally occurring beta-amino acid cispentacin. We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits. Infection was established by fluconazole-resistant (MIC > 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P

  5. In vitro synergism of a water insoluble fraction of Uncaria tomentosa combined with fluconazole and terbinafine against resistant non-Candida albicans isolates.

    Science.gov (United States)

    Moraes, Renata Cougo; Carvalho, Anderson Ramos; Lana, Aline Jacobi Dalla; Kaiser, Samuel; Pippi, Bruna; Fuentefria, Alexandre Meneghello; Ortega, George González

    2017-12-01

    Uncaria tomentosa D.C. (Rubiaceae) has several biological activities, including activity against resistant Candida strains. The synergistic interaction with terbinafine or fluconazole can be an important alternative to overcome this resistance. The potential synergy between a water insoluble fraction (WIF) from Uncaria tomentosa bark and the antifungals terbinafine (TRB) and fluconazole (FLZ) against non-Candida albicans resistant strains was investigated. TRB and FLZ, alone and combined with WIF, were tested by the checkerboard procedure using the micro-dilution technique against seven isolates of Candida glabrata and C. krusei. The molecular interactions occurring outside the cell wall were evaluated by scanning electron microscopy, Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) analysis. The checkerboard inhibitory assay demonstrated synergy for WIF:TRB and WIF:FLZ combinations, respectively. The best synergistic cell damage was demonstrated unequivocally for the associations of WIF and TRB (1.95:4.0 μg/mL) and WIF and FLZ (1.95:8.0 μg/mL). The comparison of the FT-IR spectra of the antifungal alone, and in combination with WIF, allows recognizing clear differences in 3000, 1600, 1400, and 700-800 cm -1 bands. Additionally, modifications on TRB and FLZ thermograms were clearly noticed after their combination with WIF. DSC and infrared analysis demonstrated intermolecular interactions between WIF and either TRB or FLZ. Hence, quite likely the synergistic effect is related to interaction events occurring outside the cell wall between antifungal and cat's claw proanthocyanidins. A direct action on the cell wall is suggested, without connection with the ABC efflux pump mechanism.

  6. [Comparison of microdilution and disk diffusion methods for the detection of fluconazole and voriconazole susceptibility against clinical Candida glabrata isolates and determination of changing susceptibility with new CLSI breakpoints].

    Science.gov (United States)

    Hazırolan, Gülşen; Sarıbaş, Zeynep; Arıkan Akdağlı, Sevtap

    2016-07-01

    Candida albicans is the most frequently isolated species as the causative agent of Candida infections. However, in recent years, the isolation rate of non-albicans Candida species have increased. In many centers, Candida glabrata is one of the commonly isolated non-albicans species of C.glabrata infections which are difficult-to-treat due to decreased susceptibility to fluconazole and cross-resistance to other azoles. The aims of this study were to determine the in vitro susceptibility profiles of clinical C.glabrata isolates against fluconazole and voriconazole by microdilution and disk diffusion methods and to evaluate the results with both the previous (CLSI) and current species-specific CLSI (Clinical and Laboratory Standards Institute) clinical breakpoints. A total of 70 C.glabrata strains isolated from clinical samples were included in the study. The identification of the isolates was performed by morphologic examination on cornmeal Tween 80 agar and assimilation profiles obtained by using ID32C (BioMérieux, France). Broth microdilution and disk diffusion methods were performed according to CLSI M27-A3 and CLSI M44-A2 documents, respectively. The results were evaluated according to CLSI M27-A3 and M44-A2 documents and new vs. species-specific CLSI breakpoints. By using both previous and new CLSI breakpoints, broth microdilution test results showed that voriconazole has greater in vitro activity than fluconazole against C.glabrata isolates. For the two drugs tested, very major error was not observed with disk diffusion method when microdilution method was considered as the reference method. Since "susceptible" category no more exists for fluconazole vs. C.glabrata, the isolates that were interpreted as susceptible by previous breakpoints were evaluated as susceptible-dose dependent by current CLSI breakpoints. Since species-specific breakpoints remain yet undetermined for voriconazole, comparative analysis was not possible for this agent. The results obtained

  7. Potent Antifungal Activity of Pure Compounds from Traditional Chinese Medicine Extracts against Six Oral Candida Species and the Synergy with Fluconazole against Azole-Resistant Candida albicans

    Directory of Open Access Journals (Sweden)

    Zhimin Yan

    2012-01-01

    Full Text Available This study was designed to evaluate the in vitro antifungal activities of four traditional Chinese medicine (TCM extracts. The inhibitory effects of pseudolaric acid B, gentiopicrin, rhein, and alion were assessed using standard disk diffusion and broth microdilution assays. They were tested against six oral Candida species, Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, Candida dubliniensis, and Candida guilliermondii, including clinical isolates from HIV-negative, HIV-positive, and Sjögren's syndrome patients. It was found that pseudolaric acid B had the most potent antifungal effect and showed similar antifungal activity to all six Candida spp, and to isolates from HIV-negative, HIV-positive, and Sjögren's syndrome patients. The MIC values ranged from 16 to 128 μg/mL. More interestingly, a synergistic effect of pseudolaric acid B in combination with fluconazole was observed. We suggest that pseudolaric acid B might be a potential therapeutic fungicidal agent in treating oral candidiasis.

  8. Calcium-activated-calcineurin reduces the In vitro and In vivo sensitivity of fluconazole to Candida albicans via Rta2p.

    Directory of Open Access Journals (Sweden)

    Yu Jia

    Full Text Available Due to the emergence of drug-resistance, first-line therapy with fluconazole (FLC increasingly resulted in clinical failure for the treatment of candidemia. Our previous studies found that in vitro RTA2 was involved in the calcineurin-mediated resistance to FLC in C. albicans. In this study, we found that calcium-activated-calcineurin significantly reduced the in vitro sensitivity of C. albicans to FLC by blocking the impairment of FLC to the plasma membrane via Rta2p. Furthermore, we found that RTA2 itself was not involved in C. albicans virulence, but the disruption of RTA2 dramatically increased the therapeutic efficacy of FLC in a murine model of systemic candidiasis. Conversely, both re-introduction of one RTA2 allele and ectopic expression of RTA2 significantly reduced FLC efficacy in a mammalian host. Finally, we found that calcium-activated-calcineurin, through its target Rta2p, dramatically reduced the efficacy of FLC against candidemia. Given the critical roles of Rta2p in controlling the efficacy of FLC, Rta2p can be a potential drug target for antifungal therapies.

  9. Antifungals susceptibility pattern of Candida spp . isolated from ...

    African Journals Online (AJOL)

    The highest susceptibility of the isolates was seen for nystatin 62 (83.78%), ketoconazole 61 (82.43%) and fluconazole 60 (81.08%). Conclusion: Despite the noticeable resistance of Candida spp. isolates to miconazole and itraconazole, the results indicate that nystatin, ketoconazole and fluconazole are the drugs of choice ...

  10. Update from a twelve-year nationwide fungaemia surveillance

    DEFF Research Database (Denmark)

    Astvad, K M T; Johansen, H K; Røder, B L

    2018-01-01

    countries. This was particularly true for the fluconazole and itraconazole use in the primary healthcare sector which exceeded the combined national use of these compounds in each of the other Nordic countries. Fluconazole susceptibility decreased (68.5%, 65.2% and 60.6% in 2004-7, 2008-11 and 2012...

  11. Time-of-flight mass spectrometry assessment of fluconazole and climbazole UV and UV/H2O2 degradability: Kinetics study and transformation products elucidation.

    Science.gov (United States)

    Castro, Gabriela; Casado, Jorge; Rodríguez, Isaac; Ramil, María; Ferradás, Aida; Cela, Rafael

    2016-01-01

    The efficiency of UV irradiation for the removal of the antimycotic drugs fluconazole (FCZ) and climbazole (CBZ) from water samples is evaluated. Degradation experiments, at laboratory scale, were carried out with spiked aliquots of ultrapure water solutions and treated wastewater samples using low-pressure mercury lamps emitting at 254 nm. Time course of precursor pollutants and identification of arising transformation products (TPs) was performed by injection of different reaction time aliquots in a liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) system. Chemical structures of identified TPs were proposed from their full-product ion spectra, acquired using different collision energies. During UV irradiation experiments, the half-lives (t1/2) of FCZ and CBZ were similar in ultrapure water solutions and wastewater samples; however, the first species was more recalcitrant than the second one. Four TPs were identified in case of FCZ resulting from substitution of fluorine atoms by hydroxyl moieties and intramolecular cyclization with fluorine removal. CBZ interacted with UV radiation through reductive dechlorination, hydroxylation and cleavage of the ether bond; moreover, five additional primary TPs, with the same empirical formula as CBZ, were also noticed. Given the relatively long t1/2 of FCZ under direct photolysis (ca. 42 min), UV irradiation was combined with H2O2 addition to promote formation of reactive hydroxyl radicals. Under such conditions, the degradation rate of FCZ was enhanced significantly and no TPs were detected. These latter conditions allowed also the effective removal of CBZ TPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Ensaio de dissolução de cápsulas de fluconazol: problemas encontrados na determinação por espectrofotometria na região do UV

    Directory of Open Access Journals (Sweden)

    D.M. Oliveira

    2010-11-01

    Full Text Available

    Entre as classes terapêuticas analisadas no Programa Nacional de Verificação da Qualidade de Medicamentos (PROVEME, o antifúngico fluconazol constava na apresentação de cápsulas de diferentes procedências. Na realização dos ensaios de dissolução conforme as técnicas dos fabricantes, constatou-se que os valores obtidos por espectrofotometria-UV foram superiores aos obtidos nos ensaios de teor e uniformidade de conteúdo, cuja determinação foi por CLAE-UV. Considerando este fato, foi objetivo deste trabalho realizar o ensaio de dissolução destas amostras pelos respectivos métodos dos fabricantes e o quantitativo do ensaio por espectrofotometria no UV e por CLAE-UV, a fim de avaliar as possíveis interferências dos excipientes nestas determinações. Os valores obtidos por espectrofotometria foram superiores aos obtidos por CLAE, confirmando a interferência dos excipientes. Concluiu-se que a metodologia a ser empregada na análise de fármacos deve ser criteriosamente selecionada, a fim de evitar resultados não condizentes com a real formulação do produto. Palavras-chave: cápsulas de fluconazol, CLAE, dissolução, espectrofotometria. ABSTRACT Among the therapeutic classes analyzed in the Programa Nacional de Verificação da Qualidade de Medicamentos (PROVEME consisted the antifungal fluconazole in the dosage form of capsules from different origins. In dissolution tests, according to manufacturers techniques, it was found that the values obtained by UV-spectrophotometry were higher than those obtained from tests of content and content uniformity, whose determination was by HPLC-UV. Considering this fact, the objective of this study was to perform the dissolution test of these samples by the respective manufacturers methods and the quantitative assay by UV-spectrophotometry and HPLC-UV, to evaluate possible interferences of excipients in these determinations. The values obtained by spectrophotometry were

  13. Synthesis, characterization, and in vitro activity against Candida spp. of fluconazole encapsulated on cationic and conventional nanoparticles of poly(lactic-co-glycolic acid

    Directory of Open Access Journals (Sweden)

    Gómez-Sequeda N

    2017-05-01

    Full Text Available Nicolás Gómez-Sequeda,1 Rodrigo Torres,2 Claudia Ortiz3 1School of Biology, 2School of Chemistry, Faculty of Sciences, 3School of Microbiology, Faculty of Health, Universidad Industrial de Santander, Bucaramanga, Santander, Colombia Abstract: In this study, nanoparticles (NPs of poly(lactic-co-glycolic acid (PLGA loaded with fluconazole (FLZ and FLZ-NPs coated with the cationic polymer polyethylenimine (PEI (FLZ-NP-PEI were synthetized in order to improve antimycotic activity against four strains of Candida spp. of clinical relevance. FLZ-NPs and FLZ-NP-PEI were synthesized by double emulsion solvent-diffusion (DES-D and characterized. Minimum inhibitory concentration (MIC50 and minimum fungicide concentration (MFC were determined in vitro by culturing Candida strains in the presence of these nanocompounds. FLZ-NPs were spherical in shape with hydrodynamic sizes of ~222 nm and surface charge of -11.6 mV. The surface charges of these NPs were successfully modified using PEI (FLZ-NP-PEI with mean hydrodynamic sizes of 281 nm and surface charge of 23.5 mV. The efficiency of encapsulation (~53% and a quick release of FLZ (≥90% after 3 h were obtained. Cytotoxicity assay showed a good cell viability for FLZ-NPs (≥86%, and PEI-modified NPs presented a decrease in cell viability (~38%. FLZ-NPs showed an increasing antifungal activity of FLZ for sensitive (Candida parapsilosis ATCC22019 and Candida albicans ATCC10231, MIC50 =0.5 and 0.1 µg/mL, respectively and resistant strains (Candida glabrata EMLM14 and Candida krusei ATCC6258, MIC50 =0.1 and 0.5 µg/mL, respectively. FLZ-NP-PEI showed fungicidal activity even against C. glabrata and C. krusei (MFC =4 and 8 µg/mL, respectively. MIC50 values showed best results for FLZ-NPs and FLZ-NP-PEI. Nevertheless, only FLZ-NP-PEI displayed fungicidal activity against the studied strains. Keywords: drug delivery systems, double emulsion diffusion, nanoparticles, minimal inhibitory concentration

  14. Comparison of the Vitek 2 yeast susceptibility system with CLSI microdilution for antifungal susceptibility testing of fluconazole and voriconazole against Candida spp., using new clinical breakpoints and epidemiological cutoff values.

    Science.gov (United States)

    Pfaller, Michael A; Diekema, Daniel J; Procop, Gary W; Rinaldi, Michael G

    2013-09-01

    A commercially available, fully automated yeast susceptibility test system (Vitek 2; bioMérieux, Marcy d'Etoile, France) was compared in 3 different laboratories with the Clinical and Laboratory Standards Institute (CLSI) reference microdilution (BMD) method by testing 2 quality control strains, 10 reproducibility strains, and 425 isolates of Candida spp. against fluconazole and voriconazole. Reference CLSI BMD MIC endpoints and Vitek 2 MIC endpoints were read after 24 hours and 9.1-27.1 hours incubation, respectively. Excellent essential agreement (within 2 dilutions) between the reference and Vitek 2 MICs was observed for fluconazole (97.9%) and voriconazole (96.7%). Categorical agreement (CA) between the 2 methods was assessed using the new species-specific clinical breakpoints (CBPs): susceptible (S) ≤2 μg/mL, susceptible dose-dependent (SDD) 4 μg/mL, and resistant (R) ≥8 μg/mL for fluconazole and Candida albicans, Candida tropicalis, and Candida parapsilosis and ≤32 μg/mL (SDD), ≥64 μg/mL (R) for Candida glabrata; S ≤0.12 μg/mL, SDD 0.25-0.5 μg/mL, R ≥1 μg/mL for voriconazole and C. albicans, C. tropicalis, and C. parapsilosis, and ≤0.5 μg/mL (S), 1 μg/mL (SDD), ≥2 μg/mL (R) for Candida krusei. The epidemiological cutoff value (ECV) of 0.5 μg/mL for voriconazole and C. glabrata was used to differentiate wild-type (WT; MIC ≤ ECV) from non-WT (MIC > ECV) strains of this species. Due to the lack of CBPs for the less common species, the ECVs for fluconazole and voriconazole, respectively, were used for Candida lusitaniae (2 μg/mL and 0.03 μg/mL), Candida dubliniensis (0.5 μg/mL and 0.03 μg/mL), Candida guilliermondii (8 μg/mL and 0.25 μg/mL), and Candida pelliculosa (4 μg/mL and 0.25 μg/mL) to categorize isolates of these species as WT and non-WT. CA between the 2 methods was 96.8% for fluconazole and 96.5% for voriconazole with less than 1% very major errors and 1.3-3.0% major errors. The Vitek 2 yeast susceptibility system

  15. [Susceptibility of yeasts to antifungal agents in Kaunas University of Medicine Hospital].

    Science.gov (United States)

    Skrodeniene, Erika; Dambrauskiene, Asta; Vitkauskiene, Astra

    2006-01-01

    The aim of this study was to determine the species of yeast and their susceptibility to antifungal agents isolated from clinical specimens of patients treated in Kaunas University of Medicine Hospital. A total of 142 yeasts isolated from various clinical specimens of patients hospitalized in Kaunas University of Medicine Hospital were included in this study. All yeasts were cultivated on Sabouraud dextrose agar and identified using either CHROM agar or API 20C AUX system. The minimum inhibitory concentrations of fluconazole, itraconazole, and amphotericin B were determined by the ATB FUNGUS 2 agar microdilution test. In all clinical specimens except blood, Candida albicans was the most frequently isolated yeast (65.5%, pyeast strains showed resistance to fluconazole. Nearly one-fourth of Candida albicans strains (24.7%) and 23.2% of all isolated yeast strains showed resistance to itraconazole. Almost all of fluconazole-resistant (93.3%) and 12.6% of fluconazole-susceptible yeast were found to be resistant to itraconazole (pyeast strains were susceptible to amphotericin B. Candida albicans strains were significantly frequently resistant to fluconazole than non-albicans Candida species (15.1% and 4.1%, respectively, pyeast isolated in Kaunas University of Medicine Hospital. There was determined that yeasts resistant to fluconazole were commonly resistant to itraconazole too. All isolated yeast strains were susceptible to amphotericin B.

  16. Motorcycle Parts

    Science.gov (United States)

    1993-01-01

    An article in NASA Tech Briefs describing a vacuum bagging process for forming composite parts helped a small Oklahoma Company to improve its manufacturing process. President of Performance Extremes, Larry Ortega, and his partners make motorcycle parts from carbon/epoxy to reduce weight. Using vacuum bags, parts have a better surface and fewer voids inside. When heat used in the vacuum bag process caused deformation upon cooling, a solution found in another tech brief solved the problem. A metal plate inside the vacuum bag made for more even heat transfer. A third article described a simple procedure for repairing loose connector pins, which the company has also utilized.

  17. Seminational surveillance of fungemia in Denmark: notably high rates of fungemia and numbers of isolates with reduced azole susceptibility

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Fuursted, Kurt; Gahrn-Hansen, Bente

    2005-01-01

    laboratory systems documented a continuous increase of candidemia cases since the early 1990s. For the 272 susceptibility-tested isolates, MICs of amphotericin B and caspofungin were within the limits expected for the species or genus. However, decreased azole susceptibility, defined as a fluconazole MIC...... of >8 microg/ml and/or itraconazole MIC of >0.125 microg/ml, was detected for 11 Candida isolates that were neither C. glabrata nor C. krusei. Including intrinsically resistant fungi, we detected decreased susceptibility to fluconazole and/or itraconazole in 87 (32%) current Danish bloodstream fungal...... isolates. We showed a continuous increase of fungemia in Denmark and an annual rate in 2003 to 2004 higher than in most other countries. The proportion of bloodstream fungal isolates with reduced susceptibility to fluconazole and/or itraconazole was also notably high....

  18. Part two

    DEFF Research Database (Denmark)

    Nielsen, Mads Pagh; Kær, Søren Knudsen; Korsgaard, Anders

    2008-01-01

    A novel micro combined heat and power system and a dynamic model thereof were presented in part one of the publication. In the following, the control system and dynamic performance of the system are presented. The model is subjected to a measured consumption pattern of 25 Danish single family...... houses with measurements of heat, power and hot water consumption every 15th minute during one year. Three scenarios are analyzed ranging from heat following only (grid compensation for electricity) to heat and power following with net export of electricity during high and peak load hours. Average...

  19. Evaluation of Susceptibility of Strains of Candida Albicans Isolated from AIDS Patients to Fluconazole and Determination of CDR2 Resistance Gene in Resistant Strains by RT-PCR Method

    Directory of Open Access Journals (Sweden)

    E Farahbakhsh

    2011-08-01

    Full Text Available Introduction & Objective: Nowadays, opportunistic fungi especially Candida albicans are the most common cause of life-threatening infections in immunodeficiency patients. Increasing Azole-resistant strains of C.albicans are a main problem in human immunodeficiency virus-infected patients. The aim of this study was to evaluate the CDR2 gene in C.albicans azole resistant strains, isolated from AIDS patients with oropharyngeal candidiasis by RT-PCR method. Materials & Methods: The present experimental study was conducted at Tarbiat Modares University of Medical Sciences in 2009. C. albicans isolates from HIV infected patients were identified by standard procedures, including germ tube formation, clamidospor and color of colonies on CHROM agar. At first, susceptibility of C. albicans isolates was assessed by disk diffusion agar technique. Then, CDR2 resistance gene was analyzed by RT-PCR and electrophoresis of the PCR products. Finally, patterns of the resulted bands were compared with standard fluconazole resistant strains. The collected data was analyzed using the SPSS software. Results: The results of drug sensitivity of 66 C. albicans isolates from AIDS patients revealed that 62.6% were susceptible, 8.6% were susceptible-dose dependent (SDD and 28.7% were resistant. In RT-PCR analysis, 6% of patients had the CDR2 gene. Conclusion: The use of phenotypic methods like disk diffusion agar, which is cheaper, along with genotypic methods, like RT-PCR, which provide the possibility of studying the mechanism of drug resistance, is recommended.

  20. Immunomodulatory activity of itraconazole in lung

    African Journals Online (AJOL)

    1Escuela de Ciencias de la Salud, Universidad Pontificia Bolivariana, 2Unidad de Micología Médica y Experimental,. Corporación ..... presence of local effector cells and the cytokine milieu that ... Desarrollo y la Innovación de la Universidad.

  1. Immunomodulatory activity of itraconazole in lung

    African Journals Online (AJOL)

    Methods: Two experimental groups consisting of 25 BALB/c mice each were used: (a) PBS-treated mice and (b) ... only in developing new antifungal drugs but also ... development of adaptive immunity, which ..... Annals of the New York.

  2. (segunda parte

    Directory of Open Access Journals (Sweden)

    José María Oliva-Martínez

    2004-01-01

    Full Text Available Este trabajo es la continuación de otro anterior (Oliva, 2004, ambos dedicados al estudio de la importancia del pensamiento analógico en la construcción histórica de la noción de fuerza gravitatoria y del modelo de Sistema Solar. En aquella ocasión analizamos dicho papel durante el período comprendido desde las antiguas civilizaciones hasta llegar a la revolución copernicana con científicos como Copérnico, Gilbert, Kepler o el propio Galileo. En esta segunda parte, se continúa con algunos de los razonamientos analógicos proporcionados desde la vertiente mecanicista, capitaneada por Descartes y desde la tradición subsiguiente que se desarrolló en línea con la utilización del método de la analogía como criterio argumentativo (Huyghens, Hooke, Bernoulli, etc.. Dedicamos asimismo un capítulo aparte a la figura de Newton, quien continúa con dicha tradición en su intento de explicar la naturaleza de la gravitación. Finalmente se procede, a modo de síntesis, a realizar una clasificación de distintos tipos de razonamientos analógicos aportados en el desarrollo histórico en torno a estos temas, estudiando el papel científico y divulgativo de cada uno

  3. Epidemiology, pathology and treatment of cutaneous leishmaniasis in taif region of saudi arabia.

    Directory of Open Access Journals (Sweden)

    Wajihullah Khan

    2014-09-01

    Full Text Available Cutaneous leishmaniasis is an annoying and disfiguring disease affecting around 1,500,000 individuals globally. There are endemic pockets of this disease in Taif region. In some patients, lesion often weeps and leads to scar formation. The study was conducted to see the efficacy of fluconazole and itraconazole in the patients of cutaneous leishmaniasis and the effect of these drugs on liver enzymes and kidney markers.Positivity of Leishmania was recorded by microscopic examinations of smears. Specific diagnosis for Leishmania major and L. tropica was made with the help of nested polymerase chain reaction. Fluconazole was given at the rate of 200mg/day while itraconazole was given at 150mg/day for six weeks. AST, ALT, creatinine and urea were estimated during medication.Leishmania major and L. tropica were the species responsible for cutaneous leishmaniasis in Taif region. 81% patients had single lesions, mostly on face followed by hands and legs. 15% of the lesions had bacterial contamination. In terms of efficacy, fluconazole gave slightly better results compared to itraconazole. After 6 weeks of medications, slightly elevated values were recorded for liver enzymes and creatinine.Transmission of leishmaniasis in Taif region is probably because of poor coverage of residual insecticides spraying at hiding places in pile-ups of rocks and abandoned houses from where sand flies visit nearby houses and cattle sheds during night. Fluconazole and itraconazole may be used for the treatment of cutaneous leishmaniasis with good recovery rate and fewer side effects.

  4. A New Flavanone from Flemingia strobilifera (Linn) R. Br. and its ...

    African Journals Online (AJOL)

    elearning

    drugs vancomycin, linezolid, fluconazole and itraconazole were defined as the lowest concentration of drug that resulted in total inhibition of microbial growth. The MIC was defined as the minimum inhibitory concentration of the extract or compound that resulted in total inhibition of microbial growth. RESULTS. The. DCM.

  5. [Fungal infections of the gastrointestinal tract].

    Science.gov (United States)

    Maragkoudakis, Emmanouil; Realdi, Giuseppe; Dore, Maria Pina

    2005-06-01

    In immunocompetent subjects fungal infections of the gastrointestinal tract are uncommon. Candida esophagitis remains the single most common fungal infection in immunocompromised hosts or in H. pylori- infected patients who receive antibiotic therapy. Enteric fungal infections are uncommon even in HIV-infected patients. Antifungal agents such as amphotericin B, ketoconazole, fluconazole, and the various formulations of itraconazole are effective for most cases.

  6. Antifungal susceptibilities of Cryptococcus neoformans.

    Science.gov (United States)

    Archibald, Lennox K; Tuohy, Marion J; Wilson, Deborah A; Nwanyanwu, Okey; Kazembe, Peter N; Tansuphasawadikul, Somsit; Eampokalap, Boonchuay; Chaovavanich, Achara; Reller, L Barth; Jarvis, William R; Hall, Gerri S; Procop, Gary W

    2004-01-01

    Susceptibility profiles of medically important fungi in less-developed countries remain uncharacterized. We measured the MICs of amphotericin B, 5-flucytosine, fluconazole, itraconazole, and ketoconazole for Cryptococcus neoformans clinical isolates from Thailand, Malawi, and the United States and found no evidence of resistance or MIC profile differences among the countries.

  7. COMPARISON OF THREE DISTINCT PROPHYLACTIC AGENTS AGAINST INVASIVE FUNGAL INFECTIONS IN PATIENTS UNDERGOING HAPLO-IDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION AND POST-TRANSPLANT CYCLOPHOSPHAMIDE

    Directory of Open Access Journals (Sweden)

    Jean Elcheikh

    2015-08-01

    Full Text Available Over the past decade, invasive fungal infections (IFI have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT. The optimal approach for prophylactic antifungal therapy has yet to be determined. We conducted a retrospective, bi-institutional comparative clinical study, and compared the efficacy and safety of micafungin 50mg/day (iv with those of fluconazole (400mg/day or itraconazole 200mg/day (iv as prophylaxis for adult patients with various haematological diseases receiving haplo-identical allogeneic stem cell transplantation (haplo. Overall, 99 patients were identified; 30 patients received micafungin, and 69 patients received fluconazole or itraconazole. After a median follow-up of 13 months (range: 5-23, Proven or probable IFIs were reported in 3 patients (10% in the micafungin group and 8 patients (12% in the fluconazole or itraconazole group. Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 5 [7%], P=0.6. A total of 4 (13% patients in the micafungin group and 23 (33% patients in the fluconazole or itraconazole group received empirical antifungal therapy (P = 0.14. No serious adverse events related to treatment were reported by patients and there was no treatment discontinuation because of drug-related adverse events in both groups. Despite the retrospective design of the study and limited sample, it contributes reassuring data to confirm results from randomised clinical trials, and to define a place for micafungin in prophylaxis after haplo.

  8. Saponins of Trifolium spp. Aerial Parts as Modulators of Candida Albicans Virulence Attributes

    Directory of Open Access Journals (Sweden)

    Aleksandra Budzyńska

    2014-07-01

    Full Text Available The aim was to provide the insight into the biology of C. albicans influenced by undescribed yet properties of saponin-rich (80%–98% fractions (SAPFs, isolated from extracts of Trifolium alexandrinum, T. incarnatum, T. resupinatum var. resupinatum aerial parts. Their concentrations below 0.5 mg/mL were arbitrarily considered as subMICs for C. albicans ATCC 10231 and were further used. SAPFs affected yeast enzymatic activity, lowered tolerance to the oxidative stress, to the osmotic stress and to the action of the cell wall disrupting agent. In their presence, germ tubes formation was significantly and irreversibly inhibited, as well as Candida invasive capacity. The evaluation of SAPFs interactions with anti-mycotics showed synergistic activity, mainly with azoles. Fluconazole MIC was lowered—susceptible C. albicans ATCC 10231 was more susceptible, and resistant C. glabrata (clinical strain become more susceptible (eightfold. Moreover, the tested samples showed no hemolytic activity and at the concentrations up to 0.5 mg/mL did not reduce viability of fibroblasts L929. This study provided the original evidence that SAPFs of Trifolium spp. aerial part exhibit significant antimicrobial activity, by reduce the expression/quantity of important Candida virulence factors and have good potential for the development of novel antifungal products supporting classic drugs.

  9. Routine versus selective antifungal administration for control of fungal infections in patients with cancer

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Johansen, Helle Krogh

    2014-01-01

    commonly used antifungal drugs decrease mortality in cancer patients with neutropenia. SEARCH METHODS: We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles. SELECTION CRITERIA: Randomised clinical trials of amphotericin B, fluconazole, ketoconazole, miconazole....... Prophylactic or empirical treatment with amphotericin B significantly decreased total mortality (relative risk (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.96), whereas the estimated RRs for fluconazole, ketoconazole, miconazole, and itraconazole were close to 1.00. No eligible trials were found.......73), fluconazole (RR 0.39, 95% CI 0.27 to 0.57) and itraconazole (RR 0.53, 95% CI 0.29 to 0.97), but not with ketoconazole or miconazole. Effect estimates were similar for those 13 trials that had adequate allocation concealment and were blinded. The reporting of harms was far too variable from trial to trial...

  10. Dermatophyte susceptibilities to antifungal azole agents tested in vitro by broth macro and microdilution methods Suscetibilidade in vitro de dermatófitos a azóis pelos métodos macro e microdiluição em caldo

    Directory of Open Access Journals (Sweden)

    Emerson Roberto Siqueira

    2008-02-01

    Full Text Available The in vitro susceptibility of dermatophytes to the azole antifungals itraconazole, fluconazole and ketoconazole was evaluated by broth macro and microdilution methods, according to recommendations of the CLSI, with some adaptations. Twenty nail and skin clinical isolates, four of Trichophyton mentagrophytes and 16 of T. rubrum were selected for the tests. Itraconazole minimal inhibitory concentrations (MIC varied from Foi avaliada a suscetibilidade in vitro de dermatófitos aos antifúngicos itraconazol, fluconazol e cetoconazol, pelos métodos macro e microdiluição em caldo, de acordo com as recomendações do CLSI, com algumas modificações. Foram estudados 20 isolados clínicos de lesões de unha e pele, sendo quatro Trichophyton mentagrophytes e 16 T. rubrum. A concentração inibitória mínima (CIM para itraconazol variou de < 0,03 a 0,25 µg/mL pelo método da macrodiluição, e de < 0,03 a 0,5 µg/mL pela microdiluição em caldo; de 0,5 a 64 µg/mL e de 0,125 a 16 µg/mL para fluconazol, respectivamente, pela macro e microdiluição; e de < 0,03 a 0,5 µg/mL por ambos os métodos para cetoconazol. A concordância entre os dois métodos (considerando ± uma diluição foi de 70% para itraconazol, 45% para fluconazol e 85% para cetoconazol. Conclui-se que os isolados estudados foram inibidos por concentrações relativamente baixas dos antifúngicos testados, e os dois métodos apresentam boa concordância, especialmente para itraconazol e cetoconazol.

  11. Fluconazole in the therapy of Pityriasis versicolor

    Directory of Open Access Journals (Sweden)

    Poljački Mirjana N.

    2005-01-01

    Full Text Available The authors present the results of the systemic application of flukonazole in therapy of Pityriasis versicolor. It was arranged for the total number of 38 patients, 18 females and 20 males. The diagnosis of diseases was established on the base of the clinical examination, the native mycological examination and by the using of Wood lamps. The therapy was passed by the using of 300 mg flukonazole in a single dose, once weekly, during two weeks. The following period amounted to one week after the passed therapy. The therapeutic efficacy was assessed with regard to the clinical and mycological healing. The clinical efficacy was assessed semiquantitative on the base of increasing of the percentage rates of the total score of disease that was computed by collecting of the numeric values for every clinical argument typical for the disease, and the mycological efficacy on the base of the mycological findings and the fluorescence finding after lightening with the Wood's lamp. The controlling examinations were performed on day 0, 14 and 22. The results of investigations have shown that the complete clinical healing was achieved after two weeks of therapy in 94,74%, and the mycological healing in 92,11% patients. The rate of the mycological healing was evaluated after 1 week of following period equal to the rate of the clinical healing and it was also 94,74%. The undesirable effects of the drug applications weren't by any patient.

  12. Part C and Part D Compliance Actions

    Data.gov (United States)

    U.S. Department of Health & Human Services — This page includes results from CMSs Past Performance Review. The report called Spring 2014 Past Performance Review Outlier Results lists MA organizations and Part D...

  13. Pushing for Part Time.

    Science.gov (United States)

    Geber, Beverly

    1987-01-01

    More employees are choosing to work part time. Although this trend started because of working women, some men are choosing part-time positions. Part-time employees forfeit salary and promotion potential, yet most feel the trade is fair and that they are more productive during their working hours. (CH)

  14. The European Confederation of Medical Mycology (ECMM) survey of candidaemia in Italy: in vitro susceptibility of 375 Candida albicans isolates and biofilm production.

    Science.gov (United States)

    Tortorano, Anna Maria; Prigitano, Anna; Biraghi, Emanuela; Viviani, Maria Anna

    2005-10-01

    To investigate the in vitro antifungal susceptibility pattern of 375 Candida albicans bloodstream isolates recovered during the European Confederation of Medical Mycology survey of candidaemia performed in Lombardia, Italy and to test the ability to form biofilm. In vitro susceptibility to flucytosine, fluconazole, itraconazole, posaconazole, voriconazole and caspofungin was performed by broth microdilution following the NCCLS guidelines. Biofilm production was measured using the XTT reduction assay in 59 isolates selected as representative of different patterns of susceptibility to flucytosine and azoles. MICs (mg/L) at which 90% of the strains were inhibited were < or =0.25 for flucytosine, 0.25 for caspofungin, 4 for fluconazole and 0.06 for itraconazole, voriconazole and posaconazole. Flucytosine resistance was detected in five isolates and was associated with serotype B in 2/29 and serotype A in 3/346. Resistance to fluconazole was detected in 10 isolates; nine of these exhibited reduced susceptibility to the other azoles. Among the 10 patients with fluconazole-resistant C. albicans bloodstream infection, only one, an AIDS patient, had been previously treated with fluconazole. Biofilm production was observed in 23 isolates (39%) and was significantly associated with serotype B. No relationship was detected with the pattern of antifungal susceptibility. Resistance is uncommon in C. albicans isolates recovered from blood cultures, while biofilm production is a relatively frequent event. Periodic surveillance is warranted to monitor the incidence of in vitro antifungal resistance as well as of biofilm production.

  15. Standard biological parts knowledgebase.

    Directory of Open Access Journals (Sweden)

    Michal Galdzicki

    2011-02-01

    Full Text Available We have created the Knowledgebase of Standard Biological Parts (SBPkb as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org. The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org. SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL, a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

  16. Standard Biological Parts Knowledgebase

    Science.gov (United States)

    Galdzicki, Michal; Rodriguez, Cesar; Chandran, Deepak; Sauro, Herbert M.; Gennari, John H.

    2011-01-01

    We have created the Knowledgebase of Standard Biological Parts (SBPkb) as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org). The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org). SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL), a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate “promoter” parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible. PMID:21390321

  17. Standard biological parts knowledgebase.

    Science.gov (United States)

    Galdzicki, Michal; Rodriguez, Cesar; Chandran, Deepak; Sauro, Herbert M; Gennari, John H

    2011-02-24

    We have created the Knowledgebase of Standard Biological Parts (SBPkb) as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org). The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org). SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL), a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

  18. Loose part monitoring device

    International Nuclear Information System (INIS)

    Nomura, Hiroshi.

    1992-01-01

    The device of the present invention estimates a place where loose parts occur and structural components as the loose parts in a fluid flow channel of a reactor device, to provide information thereof to a plant operator. That is, the device of the present invention comprises (1) a plurality of detectors disposed to each of equipments constituting fluid channels, (2) an abnormal sound sensing device for sensing signals from the detectors, (3) an estimation section for estimating the place where the loose parts occur and the structural components thereof based on the signals sensed by the abnormal sound sensing section, (4) a memory section for storing data of the plant structure necessary for the estimation, and (5) a display section for displaying the result of the estimation. In such a device, the position where the loose parts collide against the plant structural component and the energy thereof are estimated. The dropping path of the loose parts is estimated from the estimation position. Parts to be loose parts in the path are listed up. The parts on the list is selected based on the estimated energy thereby enabling to determine the loose parts. (I.S.)

  19. Controlled parts management

    International Nuclear Information System (INIS)

    Boyle, C.M.; Hidalgo, S.P.; Martinez, B.J.

    2004-01-01

    The Controlled Parts Management (CPM) system is based on industry standard practices for managing inventory. CPM is designed to record the movement of any type of inventory in a defined region referred to as an Account or SubAccount. The system is used to track the receiving, processing, storing and transfer of inventory parts. CPM provides information on parts, quantity and the exact location of the inventory. CPM is a barcode-based-part tracking system currently used to track controlled parts that are used in the R and D and testing of weapons; this tracking helps maintain the part pedigree that is required for certification of a weapon or weapon test. CPM includes bar code data collection software programmed into portable bar code readers for automating physical inventory services and remote transaction capture. CPM interfaces to other Engineering systems and supports a 'material content' of a weapons test through the test Bill of Materials and assignment of a unique inventory part in CPM. Additional functionality includes the ability to group or join parts, logically or physically and temporary or permanent, to represent discrete parts, containers, subassemblies and assemblies, and groupings.

  20. Introduction to Part 3

    DEFF Research Database (Denmark)

    Petersen, Nils Holger

    2015-01-01

    A brief contextualising discussion of Western Music History and its relations to Theological Aesthetical Thought since Carolingian Times as an introduction to 3 music articles in Part 3 of the volume.......A brief contextualising discussion of Western Music History and its relations to Theological Aesthetical Thought since Carolingian Times as an introduction to 3 music articles in Part 3 of the volume....

  1. Matrix comparison, Part 2

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg; Borlund, Pia

    2007-01-01

    The present two-part article introduces matrix comparison as a formal means for evaluation purposes in informetric studies such as cocitation analysis. In the first part, the motivation behind introducing matrix comparison to informetric studies, as well as two important issues influencing such c...

  2. Play your part

    CERN Document Server

    Ramsey, Gaynor

    1978-01-01

    Play your part is a collection of then situations in which students have to take on the roles of particular people and express their opinions, feelings or arguments about the situation. Play your part is intended for use with advanced students of English.

  3. Biostatistics primer: part I.

    Science.gov (United States)

    Overholser, Brian R; Sowinski, Kevin M

    2007-12-01

    Biostatistics is the application of statistics to biologic data. The field of statistics can be broken down into 2 fundamental parts: descriptive and inferential. Descriptive statistics are commonly used to categorize, display, and summarize data. Inferential statistics can be used to make predictions based on a sample obtained from a population or some large body of information. It is these inferences that are used to test specific research hypotheses. This 2-part review will outline important features of descriptive and inferential statistics as they apply to commonly conducted research studies in the biomedical literature. Part 1 in this issue will discuss fundamental topics of statistics and data analysis. Additionally, some of the most commonly used statistical tests found in the biomedical literature will be reviewed in Part 2 in the February 2008 issue.

  4. Workshop 96. Part III

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    Part III of the proceedings contain 155 contributions in various fields of science and technology including nuclear engineering, environmental science, and biomedical engineering. Out of these, 10 were selected to be inputted in INIS. (P.A.).

  5. Parts lubas uut muusikakooli

    Index Scriptorium Estoniae

    2005-01-01

    Peaminister Juhan Parts vastas Tallinna Muusikakeskkooli õpilase Judith Partsi kirjale Tallinna Muusikakeskkooli olukorrast lubadusega hoida silma peal Tallinna Muusikakeskkoolile, Tallinna Balletikoolile ja Georg Otsa nim. Muusikakoolile ühise hoone võimaldamisest kokkuehituseks Eesti Muusikaakadeemiaga

  6. Male hypogonadism (Part 1)

    OpenAIRE

    Ye.V. Luchytskyy; V.Yе. Luchytskyy; M.D. Tronko

    2017-01-01

    The first part of the review presents the current data on the prevalence of male hypogonadism, methods of diagnosing different forms of hypogonadism, describes the clinical manifestations of the most common forms of this disease.

  7. Male hypogonadism (Part 1

    Directory of Open Access Journals (Sweden)

    Ye.V. Luchytskyy

    2017-05-01

    Full Text Available The first part of the review presents the current data on the prevalence of male hypogonadism, methods of diagnosing different forms of hypogonadism, describes the clinical manifestations of the most common forms of this disease.

  8. Workshop 96. Part III

    International Nuclear Information System (INIS)

    1995-12-01

    Part III of the proceedings contain 155 contributions in various fields of science and technology including nuclear engineering, environmental science, and biomedical engineering. Out of these, 10 were selected to be inputted in INIS. (P.A.)

  9. Comparison between E-test and CLSI broth microdilution method for antifungal susceptibility testing of Candida albicans oral isolates Comparação entre E-test e o método da microdiluição do CLSI para teste de susceptibilidade a antifúngicos de isolados orais de Candida albicans

    Directory of Open Access Journals (Sweden)

    Cristiane Yumi Koga-Ito

    2008-02-01

    Full Text Available Thirty Candida albicans isolated from oral candidosis patients and 30 C. albicans isolated from control individuals were studied. In vitro susceptibility tests were performed for amphotericin B, fluconazole, 5-flucytosine and itraconazole through the Clinical and Laboratorial Standards Institute (CLSI reference method and E test system. The results obtained were analyzed and compared. MIC values were similar for the strains isolated from oral candidosis patients and control individuals. The agreement rate for the two methods was 66.67% for amphotericin B, 53.33% for fluconazole, 65% for flucytosine and 45% for itraconazole. According to our data, E test method could be an alternative to trial routine susceptibility testing due to its simplicity. However, it can not be considered a substitute for the CLSI reference method.Trinta Candida albicans isoladas de pacientes portadores de candidose oral e 30 Candida albicans isoladas de indivíduos controle foram estudadas. Testes de susceptibilidade in vitro foram realizados com anfotericina B, fluconazol, 5-flucitosina e itraconazol pelo método do Clinical and Laboratorial Standars Institute (CLSI e por E-test. Os resultados obtidos foram analisados e comparados. Os valores de CIM foram semelhantes para amostras isoladas de pacientes portadores de candidose oral e indivíduos controle. A concordância entre os dois métodos foi de 66,7% para a anfotericina B, 53,33% para o fluconazol, 65% para a flucitosina e 45% para o itraconazol. De acordo com estes resultados, o método do E-test poderia ser uma alternativa para a triagem de casos de rotina pela sua simplicidade. Entretanto, este método não pode ser considerado como um substituto para o método de referência do CLSI.

  10. Plutonium microstructures. Part 1

    International Nuclear Information System (INIS)

    Cramer, E.M.; Bergin, J.B.

    1981-09-01

    This report is the first of three parts in which Los Alamos and Lawrence Livermore National Laboratory metallographers exhibit a consolidated set of illustrations of inclusions that are seen in plutonium metal as a consequence of inherent and tramp impurities, alloy additions, and thermal or mechanical treatments. This part includes illustrations of nonmetallic and intermetallic inclusions characteristic of major impurity elements as an aid to identifying unknowns. It also describes historical aspects of the increased purity of laboratory plutonium samples, and it gives the composition of the etchant solutions and describes the etching procedure used in the preparation of each illustrated sample. 25 figures

  11. PHP The Good Parts

    CERN Document Server

    MacIntyre, Peter

    2010-01-01

    Get past all the hype about PHP and dig into the real power of this language. This book explores the most useful features of PHP and how they can speed up the web development process, and explains why the most commonly used PHP elements are often misused or misapplied. You'll learn which parts add strength to object-oriented programming, and how to use certain features to integrate your application with databases. Written by a longtime member of the PHP community, PHP: The Good Parts is ideal for new PHP programmers, as well as web developers switching from other languages. Become familiar w

  12. Multiple part feeding

    DEFF Research Database (Denmark)

    Hvilshøj, Mads; Bøgh, Simon; Nielsen, Oluf Skov

    2012-01-01

    " is capable of successfully servicing four part feeders in three production cells using command signals from an Open Process Control (OPC) server. Furthermore, the paper presents future research and development suggestions for AIMM, which contributes to near-term industrial maturation and implementation...

  13. Workshop 96. Part II

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    Part II of the seminar proceedings contains contributions in various areas of science and technology, among them materials science in mechanical engineering, materials science in electrical, chemical and civil engineering, and electronics, measuring and communication engineering. In those areas, 6 contributions have been selected for INIS. (P.A.).

  14. Basic Electricity. Part 3.

    Science.gov (United States)

    Kilmer, Donald C.

    Third (part 3) in a set of four guides designed for the student interested in a vocation in electrical work, this guide includes four units: Unit VI--Ohm's Law, covering six lessons (voltage, current-flow and resistance, the Ohm's Law formula, formula for finding voltage, formula for finding resistance); Unit VII--Voltages, covering five lessons…

  15. Workshop 96. Part II

    International Nuclear Information System (INIS)

    1995-12-01

    Part II of the seminar proceedings contains contributions in various areas of science and technology, among them materials science in mechanical engineering, materials science in electrical, chemical and civil engineering, and electronics, measuring and communication engineering. In those areas, 6 contributions have been selected for INIS. (P.A.)

  16. Workshop 95. Part I

    International Nuclear Information System (INIS)

    1995-12-01

    The proceedings of the seminar contain more than 420 contributions divided into 21 areas of interest. In Part I, 144 contributions are presented from the following fields: mathematics, physics, chemistry, engineering informatics and cybernetics, computer art, and fluid mechanics. For input in INIS, 15 contributions were selected from the physics section and 1 from the chemistry section. (J.B.)

  17. Workshop 95. Part I

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    The proceedings of the seminar contain more than 420 contributions divided into 21 areas of interest. In Part I, 144 contributions are presented from the following fields: mathematics, physics, chemistry, engineering informatics and cybernetics, computer art, and fluid mechanics. For input in INIS, 15 contributions were selected from the physics section and 1 from the chemistry section. (J.B.).

  18. Workshop 93. Part A

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    The aim of the seminar was to present and discuss the latest results obtained in research at the Czech Technical University and collaborating institutions. Part A of the Proceedings contains 99 contributions from the following fields: physical electronics and optics, mathematics, informatics and cybernetics, and materials engineering. Two contributions were selected for INIS. (J.B.).

  19. MIRD methodology. Part 1

    International Nuclear Information System (INIS)

    Rojo, Ana M.

    2004-01-01

    This lecture develops the MIRD (Medical Internal Radiation Dose) methodology for the evaluation of the internal dose due to the administration of radiopharmaceuticals. In this first part, the basic concepts and the main equations are presented. The ICRP Dosimetric System is also explained. (author)

  20. MIRD methodology. Part 2

    International Nuclear Information System (INIS)

    Gomez Parada, Ines

    2004-01-01

    This paper develops the MIRD (Medical Internal Radiation Dose) methodology for the evaluation of the internal dose due to the administration of radiopharmaceuticals. In this second part, different methods for the calculation of the accumulated activity are presented, together with the effective half life definition. Different forms of Retention Activity curves are also shown. (author)

  1. Machine Parts as Metaphor.

    Science.gov (United States)

    Porter, Gerald

    The connection between Language for Specific Purposes (LSP) and literature is discussed with examples of technical vocabulary drawn from a variety of writers, with particular attention to a sketch by the British dramatist Harold Pinter, "Trouble in the Works," which makes extensive use of the terminology of machine parts. It is noted…

  2. Workshop 93. Part A

    International Nuclear Information System (INIS)

    1993-01-01

    The aim of the seminar was to present and discuss the latest results obtained in research at the Czech Technical University and collaborating institutions. Part A of the Proceedings contains 99 contributions from the following fields: physical electronics and optics, mathematics, informatics and cybernetics, and materials engineering. Two contributions were selected for INIS. (J.B.)

  3. Evaluation of Etest and macrodilution broth method for antifungal susceptibility testing of Candida sp strains isolated from oral cavities of AIDS patients

    Directory of Open Access Journals (Sweden)

    SILVA Maria do Rosário R.

    2002-01-01

    Full Text Available A comparison of the Etest and the reference broth macrodilution susceptibility test for fluconazole, ketoconazole, itraconazole and amphotericin B was performed with 59 of Candida species isolated from the oral cavities of AIDS patients. The Etest method was performed according to the manufacturer's instructions, and the reference method was performed according to National Committee for Clinical Laboratory Standards document M27-A guidelines. Our data showed that there was a good correlation between the MICs obtained by the Etest and broth dilution methods. When only the MIC results at ± 2 dilutions for both methods were considered, the agreement rates were 90.4% for itraconazole, ketoconazole and amphotericin B and 84.6% for fluconazole of the C. albicans tested. In contrast, to the reference method, the Etest method classified as susceptible three fluconazole-resistant isolates and one itraconazole-resistant isolate, representing four very major errors. These results indicate that Etest could be considered useful for antifungal sensitivity evaluation of yeasts in clinical laboratories.

  4. In vitro sensitivity of medically significant Fusarium species to various antimycotics.

    Science.gov (United States)

    Sekhon, A S; Padhye, A A; Garg, A K; Ahmad, H; Moledina, N

    1994-01-01

    Sixteen isolates belonging to Fusarium chlamydosporum (n = 4), Fusarium equiseti (n = 1), Fusarium moniliforme (n = 2), Fusarium oxysporum (n = 3), Fusarium proliferatum (n = 1), and Fusarium solani (n = 5) were tested against amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, JAI-amphotericin B (water-soluble compound), hamycin and amphotericin B combined with 5-fluorocytosine, using antibiotic medium M3, high-resolution broth (pH 7.1), Sabouraud's dextrose, and yeast-nitrogen broth media (1 ml/tube). The minimal inhibitory and minimal fungicidal concentrations of 5-fluorocytosine and fluconazole for all species were > 100 micrograms/ml. All Fusarium isolates, except F. equiseti (3.125 micrograms), gave minimal inhibitory concentrations of 12.5-100 micrograms/ml for hamycin. The values for amphotericin B, itraconazole, ketoconazole, JAI-amphotericin B, and amphotericin B combined with 5-fluorocytosine were 1.56-100, 0.78-50, 3.125-100,50-100, and 1.56 to > 100 micrograms/ml, respectively. Although a wide range of minimal inhibitory concentrations was recorded for most of the isolates studied, it appears that some--F. solani, F. oxysporum, F. chlamydosporum, F. equiseti, and F. moliniforme--were more susceptible to amphotericin B, itraconazole, ketoconazole, hamycin, and amphotericin B in the presence of 5-fluorocytosine. All isolates showed resistance to 5-fluorocytosine and fluconazole. The minimal fungicidal concentrations were either the same or several times higher than the minimal inhibitory concentrations.

  5. MECHANISTIC STUDIES ON THE PHOTOTOXICITY OF ROSUVASTATIN, ITRACONAZOLE AND IMATINIB

    OpenAIRE

    Nardi, Giacomo

    2016-01-01

    Photosensitizing effects of xenobiotics are of increasing concern in public health since modern lifestyle often associates sunlight exposure with the presence of chemical substances in the skin. An important number of chemicals like perfumes, sunscreen components, or therapeutic agents have been reported as photosensitizers. In this context, a considerable effort has been made to design a model system for photosafety assessment. Indeed, screening for phototoxicity is necessary ...

  6. Concern for older parts

    International Nuclear Information System (INIS)

    Titus, E.; Spink, T.; Cookson, B.; Tenera, L.P.

    1992-01-01

    For the last half decade, regulatory expectations of the procurement process for nuclear commercial-grade safety-related materials have increase. The changes have been driven by concern for fraudulent or misrepresented parts and the loss of original equipment manufacturers. The industry responded to these concerns by developing improved procurement programs that changed how parts were specified and received and provided for verification of attributes that were critical to the successful performance of safety functions(s). Like its counterparts, Duquesne Light Company (DLCo), Beaver Valley power station began applying these enhanced requirements to procurements initiated after January 1, 1990, in response to the Nuclear Management and Resources Council initiative on dedication. Procurements prior to this data were not subject to the new requirements

  7. Workshop 93. Part B

    International Nuclear Information System (INIS)

    1993-01-01

    The aim of the seminar was to present and discuss the latest results obtained in research at the Czech Technical University and collaborating institutions. Part B of the Proceedings contains 109 contributions from the following fields: physics; medical engineering; fluid mechanics, environmental engineering, and structural mechanics. Fourteen contributions dealing with nuclear physics, plasma physics, quantum physics, nuclear chemistry, and computational physics were selected for INIS. (J.B.)

  8. Electricity Bill [Part 1

    International Nuclear Information System (INIS)

    Parkinson, C.; Hogg, N.; Salmond, A.

    1988-01-01

    The paper presents the first part of the Parliamentary debate on the second reading of the Electricity Bill, House of Commons, London 1988. The Bill sets out the government's proposals for the restructuring and privatisation of the electricity supply industry throughout Great Britain. Customers and suppliers, choice for the consumer, competition promotion, security of supply, nuclear power stations, and cost, are all discussed. (U.K.)

  9. Workshop 93. Part B

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    The aim of the seminar was to present and discuss the latest results obtained in research at the Czech Technical University and collaborating institutions. Part B of the Proceedings contains 109 contributions from the following fields: physics; medical engineering; fluid mechanics, environmental engineering, and structural mechanics. Fourteen contributions dealing with nuclear physics, plasma physics, quantum physics, nuclear chemistry, and computational physics were selected for INIS. (J.B.).

  10. Workshop 96. Part I

    International Nuclear Information System (INIS)

    1995-12-01

    The proceedings of the seminar contain nearly 500 contributions divided into 22 fields of science and technology. In Part I, 167 contributions are presented in the following areas: mathematics, physics, chemistry, engineering informatics and cybernetics, computers, and fluid mechanics. For input in INIS, 19 contributions were selected from the Physics section, 2 from the Mathematics section, and 4 from the Chemistry section. (P.A.)

  11. Workshop 96. Part I

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    The proceedings of the seminar contain nearly 500 contributions divided into 22 fields of science and technology. In Part I, 167 contributions are presented in the following areas: mathematics, physics, chemistry, engineering informatics and cybernetics, computers, and fluid mechanics. For input in INIS, 19 contributions were selected from the Physics section, 2 from the Mathematics section, and 4 from the Chemistry section. (P.A.).

  12. Endocrine system: part 1.

    Science.gov (United States)

    Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

    2014-05-27

    This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

  13. Fuel cells (part 2)

    International Nuclear Information System (INIS)

    Campanari, S.; Macchi, E.

    1999-01-01

    The article, following and completing the issues dealt with in part 1 (CH4 Energia Metano, 1/99, p. 7), describe the operating characteristic and construction features of molten carbonate and solid oxide fuel cells (MCFC and SOFC). For the latter type, construction cost are evaluated by various authors and research institutes. The article ends by presenting some tables showing the classification and the main characteristics of various fuel cells, and well as the effect of some gases on the behaviour of some of them [it

  14. Java The Good Parts

    CERN Document Server

    Waldo, Jim

    2010-01-01

    What if you could condense Java down to its very best features and build better applications with that simpler version? In this book, veteran Sun Labs engineer Jim Waldo reveals which parts of Java are most useful, and why those features make Java among the best programming languages available. Every language eventually builds up crud, Java included. The core language has become increasingly large and complex, and the libraries associated with it have grown even more. Learn how to take advantage of Java's best features by working with an example application throughout the book. You may not l

  15. R806 (part 1)

    CERN Multimedia

    CERN PhotoLab

    1976-01-01

    R806 was designed by the BNL-CERN-Syracuse-Yale Collaboration (Bill Willis spokesman) to study large transverse momentum phenomena, and installed in intersection 8 of the ISR. The main detectors were Lithium foil transition radiation detectors to identify electrons and liquid argon calorimeters to measure the energy of the electrons and photons (among the first such calorimeters to be used in an experiment). In part 1 there were two modules, top and bottom of the horizontal beam pipe; the black vertical pipe contains the cryogenics (LN2 and Lar) and is connected to the two modules with the horizontal piping.

  16. Alveolar Soft Part Sarcoma.

    Science.gov (United States)

    Jaber, Omar I; Kirby, Patricia A

    2015-11-01

    Alveolar soft part sarcoma is a rare neoplasm usually arising in the soft tissues of the lower limbs in adults and in the head and neck region in children. It presents primarily as a slowly growing mass or as metastatic disease. It is characterized by a specific chromosomal alteration, der(17)t(X:17)(p11:q25), resulting in fusion of the transcription factor E3 (TFE3) with alveolar soft part sarcoma critical region 1 (ASPSCR1) at 17q25. This translocation is diagnostically useful because the tumor nuclei are positive for TFE3 by immunohistochemistry. Real-time polymerase chain reaction to detect the ASPSCR1-TFE3 fusion transcript on paraffin-embedded tissue blocks has been shown to be more sensitive and specific than detection of TFE3 by immunohistochemical stain. Cathepsin K is a relatively recent immunohistochemical stain that can aid in the diagnosis. The recent discovery of the role of the ASPSCR1-TFE3 fusion protein in the MET proto-oncogene signaling pathway promoting angiogenesis and cell proliferation offers a promising targeted molecular therapy.

  17. Mapping sequences by parts

    Directory of Open Access Journals (Sweden)

    Guziolowski Carito

    2007-09-01

    Full Text Available Abstract Background: We present the N-map method, a pairwise and asymmetrical approach which allows us to compare sequences by taking into account evolutionary events that produce shuffled, reversed or repeated elements. Basically, the optimal N-map of a sequence s over a sequence t is the best way of partitioning the first sequence into N parts and placing them, possibly complementary reversed, over the second sequence in order to maximize the sum of their gapless alignment scores. Results: We introduce an algorithm computing an optimal N-map with time complexity O (|s| × |t| × N using O (|s| × |t| × N memory space. Among all the numbers of parts taken in a reasonable range, we select the value N for which the optimal N-map has the most significant score. To evaluate this significance, we study the empirical distributions of the scores of optimal N-maps and show that they can be approximated by normal distributions with a reasonable accuracy. We test the functionality of the approach over random sequences on which we apply artificial evolutionary events. Practical Application: The method is illustrated with four case studies of pairs of sequences involving non-standard evolutionary events.

  18. LGBTQ Youth Part 1.

    Science.gov (United States)

    Perron, Tracy; Kartoz, Connie; Himelfarb, Chaya

    2017-03-01

    In order to provide holistic care, school nurses must be culturally competent by being sensitive to health disparities experienced by students in at-risk populations. Despite the growing acceptance toward gender and sexual minorities, LGBTQ youth remain an at-risk population in our communities and our schools. School nurses as well as school counselors, social workers, and psychologists can increase their cultural competence in caring for this group of students by increasing their understanding of appropriate terminology and risks associated with this vulnerable group. This article is Part 1 of a two-article series designed to increase school nurses' abilities to advocate and care for LGBTQ youth in school settings. This first article provides information regarding proper terminology and current percentages of youth who identify as LGBTQ and concludes with implications for school nurses, including resources for nurses, school staff, and families.

  19. LGBTQ Part 2.

    Science.gov (United States)

    Perron, Tracy; Kartoz, Connie; Himelfarb, Chaya

    2017-03-01

    In addition to dealing with the normal challenges of being a teenager, many times LGBTQ youth have to deal with harassment, intimidation, and bullying on a daily basis as they disproportionately experience verbal and physical harassment while in school as a result of their sexual orientation and/or gender identity. This violence adversely affects these students' health and well-being as reflected in the depression and suicide rate among LGBTQ youth. As Part 2 of a series in articles on caring for LGBTQ youth in a school setting, this article reviews specific health risks in this group of students. School nurses can help reduce disparities in health for LGBTQ youth by understanding risk for psychological consequences of bullying and advocating for a just and responsive social school culture. Implications for school nurses include educating school staff and families as well as providing prompt and appropriate referrals for necessary psychological care.

  20. Rickets: Part I.

    Science.gov (United States)

    Shore, Richard M; Chesney, Russell W

    2013-01-01

    Rickets is characterized by impaired mineralization and ossification of the growth plates of growing children caused by a variety of disorders, the most frequent of which is nutritional deficiency of vitamin D. Despite ample knowledge of its etiology and the availability of cost-effective methods of preventing it, vitamin D deficiency rickets remains a significant problem in developing and developed countries. This two-part review covers the history, etiology, pathophysiology and clinical and radiographical findings of vitamin D deficiency rickets. Other less frequent causes of rickets and some of the disorders entering into the differential diagnoses of rickets are also considered. Controversial issues surrounding vitamin D deficiency include determination of what constitutes vitamin D sufficiency and the potential relationship between low levels of vitamin D metabolites in many individuals and unexplained fractures in infants.

  1. Job sharing. Part 1.

    Science.gov (United States)

    Anderson, K; Forbes, R

    1989-01-01

    This article is the first of a three part series discussing the impact of nurses job sharing at University Hospital, London, Ontario. This first article explores the advantages and disadvantages of job sharing for staff nurses and their supervising nurse manager, as discussed in the literature. The results of a survey conducted on a unit with a large number of job sharing positions, concur with literature findings. The second article will present the evaluation of a pilot project in which two nurses job share a first line managerial position in the Operating Room. The third article will relate the effects of job sharing on women's perceived general well being. Job sharing in all areas, is regarded as a positive experience by both nurse and administrators.

  2. Part 6: Forest monitoring

    International Nuclear Information System (INIS)

    1997-01-01

    In this part the results of forest monitoring on Hungarian and Slovak territory are presented. The two countries examine the growth and the health conditions of trees in similar ways. The monitoring sites in the Slovak and Hungarian territories, included in the joint monitoring, are shown on figure. The Slovak Party has already evaluated the wood yield data for 1996, the weekly girth growth observations in 1996 were not performed yet. So far on the Hungarian side only the weekly girth growth data are available for the year 1996, the wood yield data for 1996 are being processed. In the evaluation of Hungarian side only the results obtained for the period from 1992 to 1995 were analysed. Moreover, on the Slovak side an evaluation of the health conditions of trees based on aerial was carried out. The Hungarian party did not carried out such a survey, therefore the evaluation is based only on field (on-the-spot) observations

  3. Loose parts monitoring system

    International Nuclear Information System (INIS)

    Wakasa, Kohji; Nishida, Eiichi; Ishii, Kazuo; Yamanaka, Hiroto.

    1987-01-01

    In the loose parts monitoring system (LPMS), installed for integrity monitoring of the nuclear power plants; when there occur foreign metallic objects in the reactor primary system, including a steam generator and the piping, the sounds caused by them moving with the cooling water and thereby getting in contact with various structures are detected. Its purpose is, therefore, to detect any abnormality in the reactor plant system through such abnormal sounds due to loose or fallen supports etc., and so provide this information to the reactor operators. In principle, accelerometers are distributed in such as reactor vessel, steam generator, coolant pumps, etc., so that various sounds are collected and converted into electrical signals, followed by analysis of the data. Described are the LPMS configuration/functions, the course taken in LPMS development, future problems, etc. (Mori, K.)

  4. Fuel cycle math - part one

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This article is Part One of a two-part article that reviews some of the numbers associated with the nuclear fuel cycle. The contents of Part One include: composition of the element uranium, considering atomic mass and weight-percent of the isotopes; uranium in the ground, including ore grades; mining, with dilution factors and recovery rates; ore sorting, including concentration factors; and uranium recovery. No financial information is presented in either Part One or Part Two

  5. Candidemia in a Brazilian tertiary care hospital: species distribution and antifungal susceptibility patterns Candidemia em hospital terciário brasileiro: distribuição das espécies e padrões de susceptibilidade aos antifúngicos

    Directory of Open Access Journals (Sweden)

    Ana Graciela Ventura Antunes

    2004-10-01

    Full Text Available Recent studies have shown differences in the epidemiology of invasive infections caused by Candida species worldwide. In the period comprising August 2002 to August 2003, we performed a study in Santa Casa Complexo Hospitalar, Brazil, to determine Candida species distribution associated with candidemia and their antifungal susceptibility profiles to amphotericin B, fluconazole and itraconazole. Antifungal susceptibility was tested according to the broth microdilution method described in the NCCLS (M27A-2 method. Only one sample from each patient was analyzed (the first isolate. Most of the episodes had been caused by species other than C. albicans (51.6%, including C. parapsilosis (25.8%, C. tropicalis (13.3%, C. glabrata (3.3%, C. krusei (1.7%, and others (7.5%. Dose-dependent susceptibility to itraconazole was observed in 14.2% of strains, and dose-dependent susceptibility to fluconazole was found in 1.6%. Antifungal resistance was not found, probably related to low use of fluconazole. Further epidemiological surveillance is needed.Estudos realizados em diferentes países têm mostrado diferença na epidemiologia das infecções invasivas por Candida spp. No período de agosto de 2002 a agosto de 2003, foi conduzido estudo na Santa Casa Complexo Hospitalar, Porto Alegre, Brasil, para determinar a distribuição das espécies de Candida associadas a candidemia e o perfil de susceptibilidade das mesmas aos antifúngicos anfotericina B, fluconazol e itraconazol. Os testes de susceptibilidade foram realizados de acordo com a metodologia M27-A2 padronizada pelo NCCLS. Foi incluído no estudo o primeiro isolado de hemocultivo de cada paciente. A maioria dos episódios (51,6% ocorreu por espécies outras que C. albicans, incluindo C. parapsilosis (25,8%, C. tropicalis (13,3%, C. glabrata (3,3%, C. krusei (1,7% e outras espécies (7,5%. Não foi encontrada resistência aos antifúngicos testados, possivelmente devido ao baixo consumo de fluconazol na

  6. [Neurology! Adieau? (Part 2)].

    Science.gov (United States)

    Szirmai, Imre

    2010-05-30

    The education of neurologists is debilitated worldwide. University professors are engaged in teaching, research and patient-care. This triple challenge is very demanding, and results in permanent insecurity of University employees. To compensate for the insufficient clinical training, some institutes in the USA employ academic staff members exclusively for teaching. The formation of new subspecialties hinders the education and training of general neurologists. At present, four generations of medical doctors are working together in hospitals. The two older generations educate the younger neurologists who have been brought up in the world of limitless network of sterile information. Therefore their manual skills at the bedside and their knowledge of emergency treatment are deficient. Demographics of medical doctors changed drastically. Twice as many women are working in neurology and psychiatry than men. Integrity of neurology is threatened by: (1) Separation of the cerebrovascular diseases from general neurology. Development of "stroke units" was facilitated by the better reimbursement for treatment and by the interest of the pharmaceutical companies. Healthcare politics promoted the split of neurology into two parts. The independent status of "stroke departments" will reduce the rest of clinical neurology to outpatient service. (2) The main argumentation to segregate the rare neurological diseases was that their research will provide benefit for the diseases with high prevalence. This argumentation serves territorial ambitions. The separation of rare diseases interferes with the teaching of differential diagnostics in neurological training. The traditional pragmatic neurology can not be retrieved. The faculty of neurology could retain its integrity by the improvement of diagnostic methods and the ever more effective drugs. Nevertheless, even the progression of neurological sciences induces dissociation of clinical neurology. Neurology shall suffer fragmentation if

  7. Part I. Emergency workers

    International Nuclear Information System (INIS)

    2004-01-01

    This monograph deals with assessment of radiological health effects of the Chernobyl accident for emergency workers (part 1) and the population of the contaminated areas in Russia (part 2). The Chernobyl emergency workers and people living in the contaminated areas of Russia received much lower doses than the population of Hiroshima and Nagasaki and it was unclear whether risks of radiation-induced cancers derived with the Japanese data could be extrapolated to the low dose range However, it was predicted as early as in 1990 that the thyroid cancer incidence might be increasing due to incorporated 131 irradiation. What conclusions can be drawn from regarding cancer incidence among emergency workers and residents of the contaminated areas in Russia and the role of the radiation factor on the basis of the registry data? Leukemia incidence. Leukemia incidence is known to be one of principal indications of radiation effects. The radiation risk for leukemias is 3-4 times higher that for solid cancers and its latent period is estimated to be 2-3 years after exposure. Results of the radiation epidemiological studies discussed in this book show that in the worst contaminated Bryansk region the leukemia incidence rate is not higher than in the country in general. Even though some evidence exists for the dose response relationship, the radiation risks appear to be not statistically significant. Since risks of leukemia are known to be higher for those who were children at exposure, long-term epidemiological studies need to be continued. The study of leukemias among emergency workers strongly suggest the existence of dose response relationship. In those who received external doses more than 0.15 Gy the leukemia incidence rate is two time higher and these emergency workers should be referred to as a group of increased radiation risk. Solid cancers. The obtained results provide no evidence to a radiation-induced increase in solid cancers among residents of the contaminated areas

  8. Part II. Population

    International Nuclear Information System (INIS)

    2004-01-01

    This monograph deals with assessment of radiological health effects of the Chernobyl accident for emergency workers (part 1) and the population of the contaminated areas in Russia (part 2). The Chernobyl emergency workers and people living in the contaminated areas of Russia received much lower doses than the population of Hiroshima and Nagasaki and it was unclear whether risks of radiation-induced cancers derived with the Japanese data could be extrapolated to the low dose range However, it was predicted as early as in 1990 that the thyroid cancer incidence might be increasing due to incorporated 131 irradiation. What conclusions can be drawn from regarding cancer incidence among emergency workers and residents of the contaminated areas in Russia and the role of the radiation factor on the basis of the registry data? Leukemia incidence. Leukemia incidence is known to be one of principal indications of radiation effects. The radiation risk for leukemias is 3-4 times higher that for solid cancers and its latent period is estimated to be 2-3 years after exposure. Results of the radiation epidemiological studies discussed in this book show that in the worst contaminated Bryansk region the leukemia incidence rate is not higher than in the country in general. Even though some evidence exists for the dose response relationship, the radiation risks appear to be not statistically significant. Since risks of leukemia are known to be higher for those who were children at exposure, long-term epidemiological studies need to be continued. The study of leukemias among emergency workers strongly suggest the existence of dose response relationship. In those who received external doses more than 0.15 Gy the leukemia incidence rate is two time higher and these emergency workers should be referred to as a group of increased radiation risk. Solid cancers. The obtained results provide no evidence to a radiation-induced increase in solid cancers among residents of the contaminated areas

  9. Medicare Utilization for Part B

    Data.gov (United States)

    U.S. Department of Health & Human Services — This link takes you to the Medicare utilization statistics for Part B (Supplementary Medical Insurance SMI) which includes the Medicare Part B Physician and Supplier...

  10. Development of Aircraft Sandwich Parts

    Directory of Open Access Journals (Sweden)

    J. Křena

    2000-01-01

    Full Text Available The presented paper shows the design and development process of sandwich parts. A spoiler plate and a main landing gear door are developed. Sandwich parts are made of C/E composite facings and a foam core. FE models have been used for optimization of structures. Emphasis has been placed on deformations of parts under a few load cases. Experimental tests have been used for a verification of structure parts loaded by concentrated forces.

  11. Exploring Water Pollution. Part II

    Science.gov (United States)

    Rillo, Thomas J.

    1975-01-01

    This is part two of a three part article related to the science activity of exploring environmental problems. Part one dealt with background information for the classroom teacher. Presented here is a suggested lesson plan on water pollution. Objectives, important concepts and instructional procedures are suggested. (EB)

  12. Part Objects and Their Location

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann; Møller-Pedersen, Birger

    1992-01-01

    The notion of location of part objects is introduced, yielding a reference to the containing object. Combined with locally defined objects and classes (block structure), singularly defined part objects, and references to part objects, it is a powerful language mechanism for defining objects...

  13. Candiduria in adults and children: prevalence and antifungal susceptibility in outpatient of Jataí-GO

    Directory of Open Access Journals (Sweden)

    Izabela Alves de Sousa

    2014-08-01

    Full Text Available Introduction: The term candiduria refers to the presence of yeast in urine and Candida albicans is the most common agent. In general, routine laboratories do not perform identification and cultivation of yeast. Objectives: To determine the prevalence of Candida species and to evaluate the antifungal susceptibility of the species isolated in urine of outpatients Jataí-GO, between January-October 2013. Material and method: Urine samples containing fungal structures were plated out on Sabouraud agar with chloramphenicol. Differentiation was taken with the urease test, nitrogen and carbon sources assimilation, germ tube test, morphology on cornmeal agar and chromogenic agar cultivation. Susceptibility was evaluated at antifungal itraconazole, fluconazole, amphotericin B and ketoconazole. Results: 1,215 urine tests were performed, and 64 had fungal structures (5.3%. Two samples were lost, thus here we considered 62 isolates. From this total, 43 were identified as C. albicans (67.2 %, eight C. glabrata (12.5 %, five C. krusei (7.8%, three C. tropicalis (4.7%, and three could not determine the species (4.7%. Amphotericin B and ketoconazole inhibited 94.9% of the isolates. On the other hand, 55.9% and 54.2 % were resistant to itraconazole and fluconazole, respectively. The resistance rates of both fluconazole and itraconazole for C. glabrata and C. albicans, as fluconazole for C. albicans and C. krusei, showed significant differences (p < 0.05. Conclusion: These data demonstrate the importance of conducting a full identification and susceptibility to antifungal agents in samples with yeast infection.

  14. fluconazole and boric acid for treatment of vaginal candidiasis

    African Journals Online (AJOL)

    2013-04-01

    Apr 1, 2013 ... M. K. Khameneie, Assistant Professor, Department of Obstetrics and Gynecology, Imam Reza hospital, Tehran - Iran,. N. Arianpour ..... candidiasis. Am Fam Physician. 2000;1, 61:3306-12. 12. Donders GG, Bellen G, Mendling W. Management of recurrent vulvo-vaginal candidosis as a chronic illness.

  15. Comparison of the efficacy of fluconazole tablet and oral nystatin ...

    African Journals Online (AJOL)

    Background: Oral candidiasis is the most common HIV/AIDs related complication. It limits patients from feeding and interferes with the intake of HAART, as the patients find it difficult to swallow food and their medications. It leads to poor adherence, poor feeding, depression, loss of man hours, deterioration of patient's state of ...

  16. Intravenous Fluconazole Therapy in the Management of Intractable ...

    African Journals Online (AJOL)

    Background: Oral manifestations are among the earliest and most common clinical features seen in children and adults with HIV/AIDS. Oro-pharyngeal candidiasis, an AIDS defining illness, often heralds HIV progression, immune system deterioration and severe disability. Management is by the application of topical ...

  17. Fluconazole resistant opportunistic oro-pharyngeal candida and non ...

    African Journals Online (AJOL)

    Background: Oro-Pharyngeal Candidiasis (OPC) continues to be considered the most common opportunistic fungal disease in HIV/AIDS patients globally. Azole antifungal agent has become important in the treatment of mucosal candidiasis in HIV patients. Presently, antifungal drug resistance is fast becoming a major ...

  18. In Vitro Activity of E1210, a Novel Antifungal, against Clinically Important Yeasts and Molds▿

    Science.gov (United States)

    Miyazaki, Mamiko; Horii, Takaaki; Hata, Katsura; Watanabe, Nao-aki; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-01-01

    E1210 is a new antifungal compound with a novel mechanism of action and broad spectrum of antifungal activity. We investigated the in vitro antifungal activities of E1210 compared to those of fluconazole, itraconazole, voriconazole, amphotericin B, and micafungin against clinical fungal isolates. E1210 showed potent activities against most Candida spp. (MIC90 of ≤0.008 to 0.06 μg/ml), except for Candida krusei (MICs of 2 to >32 μg/ml). E1210 showed equally potent activities against fluconazole-resistant and fluconazole-susceptible Candida strains. E1210 also had potent activities against various filamentous fungi, including Aspergillus fumigatus (MIC90 of 0.13 μg/ml). E1210 was also active against Fusarium solani and some black molds. Of note, E1210 showed the greatest activities against Pseudallescheria boydii (MICs of 0.03 to 0.13 μg/ml), Scedosporium prolificans (MIC of 0.03 μg/ml), and Paecilomyces lilacinus (MICs of 0.06 μg/ml) among the compounds tested. The antifungal action of E1210 was fungistatic, but E1210 showed no trailing growth of Candida albicans, which has often been observed with fluconazole. In a cytotoxicity assay using human HK-2 cells, E1210 showed toxicity as low as that of fluconazole. Based on these results, E1210 is likely to be a promising antifungal agent for the treatment of invasive fungal infections. PMID:21825291

  19. Condition based spare parts supply

    NARCIS (Netherlands)

    Lin, X.; Basten, Robertus Johannes Ida; Kranenburg, A.A.; van Houtum, Geert-Jan

    2012-01-01

    We consider a spare parts stock point that serves an installed base of machines. Each machine contains the same critical component, whose degradation behavior is described by a Markov process. We consider condition based spare parts supply, and show that an optimal, condition based inventory policy

  20. Machine for dismantling metal parts

    Energy Technology Data Exchange (ETDEWEB)

    Prokopov, O.I.; Loginovskiy, V.I.; Yagudin, S.Z.

    1982-01-01

    The purpose of the invention is to reduce the outlays of time for dismantling metal parts under conditions of eliminating open gas and oil gushers in operational drilling. This goal is achieved because the machine for dismantling the metal parts is equipped with a set of clamping elements arranged on the chassis, where each of them has a drive.

  1. The MAJORANA Parts Tracking Database

    Energy Technology Data Exchange (ETDEWEB)

    Abgrall, N. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Aguayo, E. [Pacific Northwest National Laboratory, Richland, WA (United States); Avignone, F.T. [Department of Physics and Astronomy, University of South Carolina, Columbia, SC (United States); Oak Ridge National Laboratory, Oak Ridge, TN (United States); Barabash, A.S. [Institute for Theoretical and Experimental Physics, Moscow (Russian Federation); Bertrand, F.E. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Brudanin, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Busch, M. [Department of Physics, Duke University, Durham, NC (United States); Triangle Universities Nuclear Laboratory, Durham, NC (United States); Byram, D. [Department of Physics, University of South Dakota, Vermillion, SD (United States); Caldwell, A.S. [South Dakota School of Mines and Technology, Rapid City, SD (United States); Chan, Y-D. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Christofferson, C.D. [South Dakota School of Mines and Technology, Rapid City, SD (United States); Combs, D.C. [Department of Physics, North Carolina State University, Raleigh, NC (United States); Triangle Universities Nuclear Laboratory, Durham, NC (United States); Cuesta, C.; Detwiler, J.A.; Doe, P.J. [Center for Experimental Nuclear Physics and Astrophysics, and Department of Physics, University of Washington, Seattle, WA (United States); Efremenko, Yu. [Department of Physics and Astronomy, University of Tennessee, Knoxville, TN (United States); Egorov, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Ejiri, H. [Research Center for Nuclear Physics and Department of Physics, Osaka University, Ibaraki, Osaka (Japan); Elliott, S.R. [Los Alamos National Laboratory, Los Alamos, NM (United States); and others

    2015-04-11

    The MAJORANA DEMONSTRATOR is an ultra-low background physics experiment searching for the neutrinoless double beta decay of {sup 76}Ge. The MAJORANA Parts Tracking Database is used to record the history of components used in the construction of the DEMONSTRATOR. The tracking implementation takes a novel approach based on the schema-free database technology CouchDB. Transportation, storage, and processes undergone by parts such as machining or cleaning are linked to part records. Tracking parts provide a great logistics benefit and an important quality assurance reference during construction. In addition, the location history of parts provides an estimate of their exposure to cosmic radiation. A web application for data entry and a radiation exposure calculator have been developed as tools for achieving the extreme radio-purity required for this rare decay search.

  2. The MAJORANA Parts Tracking Database

    Science.gov (United States)

    Abgrall, N.; Aguayo, E.; Avignone, F. T.; Barabash, A. S.; Bertrand, F. E.; Brudanin, V.; Busch, M.; Byram, D.; Caldwell, A. S.; Chan, Y.-D.; Christofferson, C. D.; Combs, D. C.; Cuesta, C.; Detwiler, J. A.; Doe, P. J.; Efremenko, Yu.; Egorov, V.; Ejiri, H.; Elliott, S. R.; Esterline, J.; Fast, J. E.; Finnerty, P.; Fraenkle, F. M.; Galindo-Uribarri, A.; Giovanetti, G. K.; Goett, J.; Green, M. P.; Gruszko, J.; Guiseppe, V. E.; Gusev, K.; Hallin, A. L.; Hazama, R.; Hegai, A.; Henning, R.; Hoppe, E. W.; Howard, S.; Howe, M. A.; Keeter, K. J.; Kidd, M. F.; Kochetov, O.; Konovalov, S. I.; Kouzes, R. T.; LaFerriere, B. D.; Leon, J. Diaz; Leviner, L. E.; Loach, J. C.; MacMullin, J.; Martin, R. D.; Meijer, S. J.; Mertens, S.; Miller, M. L.; Mizouni, L.; Nomachi, M.; Orrell, J. L.; O`Shaughnessy, C.; Overman, N. R.; Petersburg, R.; Phillips, D. G.; Poon, A. W. P.; Pushkin, K.; Radford, D. C.; Rager, J.; Rielage, K.; Robertson, R. G. H.; Romero-Romero, E.; Ronquest, M. C.; Shanks, B.; Shima, T.; Shirchenko, M.; Snavely, K. J.; Snyder, N.; Soin, A.; Suriano, A. M.; Tedeschi, D.; Thompson, J.; Timkin, V.; Tornow, W.; Trimble, J. E.; Varner, R. L.; Vasilyev, S.; Vetter, K.; Vorren, K.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Young, A. R.; Yu, C.-H.; Yumatov, V.; Zhitnikov, I.

    2015-04-01

    The MAJORANA DEMONSTRATOR is an ultra-low background physics experiment searching for the neutrinoless double beta decay of 76Ge. The MAJORANA Parts Tracking Database is used to record the history of components used in the construction of the DEMONSTRATOR. The tracking implementation takes a novel approach based on the schema-free database technology CouchDB. Transportation, storage, and processes undergone by parts such as machining or cleaning are linked to part records. Tracking parts provide a great logistics benefit and an important quality assurance reference during construction. In addition, the location history of parts provides an estimate of their exposure to cosmic radiation. A web application for data entry and a radiation exposure calculator have been developed as tools for achieving the extreme radio-purity required for this rare decay search.

  3. Juhan Parts lubab investeerida teedesse / Juhan Parts ; interv. Tanel Raig

    Index Scriptorium Estoniae

    Parts, Juhan, 1966-

    2007-01-01

    Ilmunud ka: Delovõje Vedomosti 17. okt. lk. 13. Majandusminister Juhan Parts arutleb lahendamist vajavate küsimuste ja prioriteetsete investeeringute üle transpordisektoris. Lisa: Juhan Partsi kuus kuud ministrina

  4. Parts hindab oma valitsust "kolmega" / Juhan Parts ; interv. Toomas Sildam

    Index Scriptorium Estoniae

    Parts, Juhan, 1966-

    2005-01-01

    Peaminister Juhan Parts vastab küsimustele, mis puudutavad uue valitsuskoalitsiooni moodustamist. Peaminister peab oluliseks, et uus valitsus tekiks kiiresti, ning on nõus ise uue valitsuse kokku panema

  5. Otvetshajet Juhan Parts, premjer-ministr / Juhan Parts

    Index Scriptorium Estoniae

    Parts, Juhan, 1966-

    2005-01-01

    Peaminister Juhan Parts selgitab Res Publica ja valitsuse korruptsioonivastast poliitikat ning loodab, et justiitsminister Ken-Marti Vaheri pakutud strateegia võitluses korruptsiooniga ei saa koalitsiooni lagunemise põhjuseks

  6. Current issues in onychomycosis.

    Science.gov (United States)

    Trépanier, E F; Amsden, G W

    1998-02-01

    To review the epidemiology, mycology, clinical features and diagnosis, current pharmacotherapy, and pharmacoeconomics of onychomycosis. We conducted a MEDLINE search from 1966 to May 1997. References from these articles, manufacturers of the discussed antimycotics, and relevant abstracts from recent dermatology conferences were used to collect pertinent data. Data were obtained from published controlled studies and case reports. In the pharmacotherapy section, the most weight was placed on fully reported, randomized, controlled comparative trials, but abstracts and case series were included when well-controlled studies were unavailable. Onychomycosis is a common nail disorder that has a substantial impact on patients' quality of life. It is most commonly caused by dermatophytes, but yeasts and molds can also be involved. Diagnosis is made through clinical presentation, potassium hydroxide preparations, and culture of tissue/nail samples. Griseofulvin was the drug of choice for many years, but its low cure rates and the development of newer, more effective drugs made it fall out of favor. Current therapeutic alternatives include fluconazole, itraconazole, and terbinafine. Data on the use of fluconazole are limited to case series and reports. Continuous dosing of itraconazole and terbinafine are well-proven therapies. New data are becoming available on the use of pulse itraconazole dosing, which has recently been approved by the Food and Drug Administration for fingernail infections. These drugs are well tolerated, but attention to drug interactions is necessary with the azoles. Currently, continuous terbinafine appears to be the most cost-effective drug for dermatophyte onychomycosis.

  7. Overexpression of Aldo-Keto-Reductase in Azole-resistant Clinical Isolates of Candida Glabrata Determined by cDNA-AFLP

    Directory of Open Access Journals (Sweden)

    Mansour Heidari

    2013-01-01

    Full Text Available Background: Candida glabrata causes significant medical problems in immunocompromised patients. Many strains of this yeast are intrinsically resistant to azole antifungal agents, and treatment is problematic, leading to high morbidity and mortality rates in immunosuppressed individuals. The primary goal of this study was to investigate the genes involved in the drug resistance of clinical isolates of C. glabrata.Methods: The clinical isolates of C. glabrata were collected in an epidemiological survey of candidal infection inimmunocompromised patients and consisted of four fluconazole and itraconazole resistant isolates, two fluconazoleand itraconazole sensitive isolates, and C. glabrata CBS 138 as reference strain. Antifungal susceptibility patterns ofthe organisms were determined beforehand by the Clinical and Laboratory Standards Institute (CLSI. The potentialgene(s implicated in antifungal resistance were investigated using complementary DNA- Amplified Fragment Length Polymorphism (cDNA-AFLP. Semi-quantitative RT-PCR was carried out to evaluate the expression of gene(s in resistant isolates as compared to sensitive and reference strains.Results and conclusions: The aldo-keto-reductase superfamily (AKR gene was upregulated in the resistant clinicalisolates as assessed by cDNA-AFLP. Semi-quantitative RT-PCR revealed AKR mRNA expression approximately twice that seen in the sensitive isolates. Overexpression of the AKR gene was associated with increased fluconazole and itraconazole resistance in C. glabrata. The data suggest that upregulation of the AKR gene might give a new insight into the mechanism of azole resistance.

  8. Advanced modern algebra part 2

    CERN Document Server

    Rotman, Joseph J

    2017-01-01

    This book is the second part of the new edition of Advanced Modern Algebra (the first part published as Graduate Studies in Mathematics, Volume 165). Compared to the previous edition, the material has been significantly reorganized and many sections have been rewritten. The book presents many topics mentioned in the first part in greater depth and in more detail. The five chapters of the book are devoted to group theory, representation theory, homological algebra, categories, and commutative algebra, respectively. The book can be used as a text for a second abstract algebra graduate course, as a source of additional material to a first abstract algebra graduate course, or for self-study.

  9. Medicare Utilization for Part A

    Data.gov (United States)

    U.S. Department of Health & Human Services — This link takes you to the Medicare utilization statistics for Part A (Hospital Insurance HI) which include the Medicare Ranking for all Short-Stay Hospitals by...

  10. Medicare Part D Claims Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — This page contains information on Part D claims data for the purposes of research, analysis, reporting, and public health functions. These data will also be used to...

  11. VULNERABILITY OF PART TIME EMPLOYEES

    Directory of Open Access Journals (Sweden)

    Raluca Dimitriu

    2015-11-01

    Full Text Available The employee who concluded a part-time contract is the employee whose normal working hours, calculated weekly or as monthly average, is lower than the number of normal working hours of a comparable full-time employee. Part-time workers generally have the same legal status as full time workers. In fact, the vulnerability of this category of workers is not necessarily legal but rather economic: income - in proportion to the work performed, may be insufficient to cover the needs of living. However, such vulnerability may also have a certain cultural component: in some societies, professional identity is determined by the length of working hours. Also, part time work may hide many types of indirect discrimination.As a result, the part-time contract requires more than a protective legislation: it requires a strategy. This paper proposes a number of milestones of such a strategy, as well as some concrete de lege ferenda proposals.

  12. Computer-Aided Parts Estimation

    OpenAIRE

    Cunningham, Adam; Smart, Robert

    1993-01-01

    In 1991, Ford Motor Company began deployment of CAPE (computer-aided parts estimating system), a highly advanced knowledge-based system designed to generate, evaluate, and cost automotive part manufacturing plans. cape is engineered on an innovative, extensible, declarative process-planning and estimating knowledge representation language, which underpins the cape kernel architecture. Many manufacturing processes have been modeled to date, but eventually every significant process in motor veh...

  13. TSUNAMI INFORMATION SOURCES PART 3

    Directory of Open Access Journals (Sweden)

    Robert L. Wiegel

    2009-01-01

    Full Text Available This is Part 3 of Tsunami Information Sources published by Robert L. Wiegel, as Technical Report UCB/HEL 2006-3 of the Hydraulic Engineering Laboratory of the Department of Civil & Environmental Engineering of the University of California at Berkeley. Part 3 is published in "SCIENCE OF TSUNAMI HAZARDS" -with the author's permission -so that it can receive wider distribution and use by the Tsunami Scientific Community.

  14. In vitro activities of antifungal drugs against environmental Exophiala isolates and review of the literature.

    Science.gov (United States)

    Gülmez, Dolunay; Doğan, Özlem; Boral, Barış; Döğen, Aylin; İlkit, Macit; de Hoog, G Sybren; Arikan-Akdagli, Sevtap

    2018-04-03

    Exophiala is a genus of black fungi isolated worldwide from environmental and clinical specimens. Data on antifungal susceptibility of Exophiala isolates are limited and the methodology on susceptibility testing is not yet standardized. In this study, we investigated in vitro antifungal susceptibilities of environmental Exophiala isolates. A total of 87 Exophiala isolated from dishwashers or railway ties were included. CLSI M38-A2 microdilution method with modifications was used to determine antifungal susceptibility for fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B, and terbinafine. Minimum inhibitory concentration (MIC) values were determined visually at 48h, 72h, and 96h. MIC-0 endpoint (complete inhibition of growth) was used for amphotericin B and azoles, except fluconazole, for which MIC-2 endpoint (~50% inhibition compared to growth control) was used. Both MIC-0 and MIC-1 (~80% inhibition compared to growth control) results were analysed for terbinafine, to enable comparison with previous studies. Fungal growth was sufficient for determination of MICs at 48h for all isolates except two Exophiala dermatitidis strains. At 72h, most active antifungal agents according to GM MIC were voriconazole and terbinafine, followed by posaconazole, itraconazole, and amphotericin B in rank order of decreasing activity. While amphotericin B displayed adequate in vitro activity despite relatively high MICs, fluconazole showed no meaningful antifungal activity against Exophiala. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. In Vitro Antifungal Susceptibility of Oral Candida Isolates from Patients Suffering from Caries and Chronic Periodontitis.

    Science.gov (United States)

    De-la-Torre, Janire; Ortiz-Samperio, María Esther; Marcos-Arias, Cristina; Marichalar-Mendia, Xabier; Eraso, Elena; Echebarria-Goicouria, María Ángeles; Aguirre-Urizar, José Manuel; Quindós, Guillermo

    2017-06-01

    Caries and chronic periodontitis are common oral diseases where a higher Candida colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral Candida isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral Candida isolates (75 Candida albicans, 18 Candida parapsilosis, 11 Candida dubliniensis, six Candida guilliermondii, five Candida lipolytica, five Candida glabrata, four Candida tropicalis and two Candida krusei) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.

  16. Parts : ministrite minevik olgu avalik / Juhan Parts ; interv. Toomas Sildam

    Index Scriptorium Estoniae

    Parts, Juhan, 1966-

    2003-01-01

    Peaminister Juhan Parts vastab küsimustele, mis on seotud politseinike altkäemaksu andmise avalikuks tulekuga, komissar Indrek Sirgi ametist lahkumisega ja ministrite seadusrikkumiste avalikustamisega. Kommenteerivad: Margus Leivo, Tarmo Loodus, Ain Seppik. Vt. samas: Valik saladuses peetavast teabest

  17. Calculus: A Computer Oriented Presentation, Part 1 [and] Part 2.

    Science.gov (United States)

    Stenberg, Warren; Walker, Robert J.

    Parts one and two of a one-year computer-oriented calculus course (without analytic geometry) are presented. The ideas of calculus are introduced and motivated through computer (i.e., algorithmic) concepts. An introduction to computing via algorithms and a simple flow chart language allows the book to be self-contained, except that material on…

  18. Dynamic loading of galvanized parts

    Directory of Open Access Journals (Sweden)

    Michal Černý

    2010-01-01

    Full Text Available This work is divided into two parts: the theoretical part includes actual knowledge and points of view about degradation processes in construction materials, anticorrosion protection, zinc coat composition and high frequency fatigue. The laboratory part follow-up existing regulations contents Czech standards and formulate specifications for acquisition of objective information from acceleration la­bo­ra­to­ry tests in condensation chests, mechanical high frequency fatigue tests on pulsator machine and possibilities of evaluation of fatigue tests. Laboratory findings declare to fundamental types of damage of constructions with anticorrosion protection in real loading conditions with dynamic high frequency character. Laboratory tests were made in sulphide and chloride environments.

  19. Function Concepts for Machine Parts

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik

    1999-01-01

    The majority of resources, like time and costs, consumed in industrial product development can be related to detailed design, i.e. the materialisation of machine parts (German Maschinenteile). Existing design theories based on a systems approach, e.g. Haberfellner [5] all have function, i.......e. transformation from input to output or ability to deliver purposeful effects as the core concept. The units in a product which posses functions are the organs (German: Funktionsträgern). Because individual parts do not posses functions, one could argue that the design theories based on a systems approach...... to be identification of a purposeful behaviour concept, i.e. function for a machine part. The contribution is based on the theory of technical systems, Hubka and the domain theory, Andreasen....

  20. Update on rheumatology: part 1.

    Science.gov (United States)

    Neal-Boylan, Leslie

    2009-05-01

    There are many rheumatic diseases. Part 1 of this 2 part series on rheumatology presented a few of those most commonly seen in the community. Home health clinicians can be helpful in managing these diseases and preventing progression by watching for new symptoms or acute attacks of pain or disability, ensuring that patients take their medications appropriately, reminding patients to see their rheumatology providers and have their lab work done regularly, and reporting adverse effects to medications promptly. Additionally, as with most home health patients, an interdisciplinary approach that includes physical and occupational therapy, social work, nursing, nutrition, and other disciplines as needed should be implemented so that all patient needs are met and the patient is discharged at the highest level of self-care that is possible. Part 2 of this series will discuss the care of the patient with rheumatic disease at home and will provide a more in-depth look at lab diagnosis of rheumatic diseases.

  1. Understanding quantitative research: part 1.

    Science.gov (United States)

    Hoe, Juanita; Hoare, Zoë

    This article, which is the first in a two-part series, provides an introduction to understanding quantitative research, basic statistics and terminology used in research articles. Critical appraisal of research articles is essential to ensure that nurses remain up to date with evidence-based practice to provide consistent and high-quality nursing care. This article focuses on developing critical appraisal skills and understanding the use and implications of different quantitative approaches to research. Part two of this article will focus on explaining common statistical terms and the presentation of statistical data in quantitative research.

  2. Grinding Parts For Automatic Welding

    Science.gov (United States)

    Burley, Richard K.; Hoult, William S.

    1989-01-01

    Rollers guide grinding tool along prospective welding path. Skatelike fixture holds rotary grinder or file for machining large-diameter rings or ring segments in preparation for welding. Operator grasps handles to push rolling fixture along part. Rollers maintain precise dimensional relationship so grinding wheel cuts precise depth. Fixture-mounted grinder machines surface to quality sufficient for automatic welding; manual welding with attendant variations and distortion not necessary. Developed to enable automatic welding of parts, manual welding of which resulted in weld bead permeated with microscopic fissures.

  3. SPSS for Starters, Part 2

    CERN Document Server

    Cleophas, Ton J

    2012-01-01

    The first part of this title contained all statistical tests that are relevant for starters on SPSS, and included standard parametric and non-parametric tests for continuous and binary variables, regression methods, trend tests, and reliability and validity assessments of diagnostic tests. The current part 2 of this title reviews multistep methods, multivariate models, assessments of missing data, performance of diagnostic tests, meta-regression, Poisson regression, confounding and interaction, and survival analyses using log tests and segmented time-dependent Cox regression. Methods for asses

  4. Fuel cycle math - part two

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This article is Part 2 of a two part series on simple mathematics associated with the nuclear fuel cycle. While not addressing any of the financial aspects of the fuel cycle, this article does discuss the following: conversion between English and metric systems; uranium content expressed in equivalent forms, such as U3O8, and the method of determining these equivalencies; the uranium conversion process, considering different input and output compounds; and the enrichment process, including feed, tails, and product assays, as well as SWU and feed requirements

  5. Magnetic fusion energy. Part VI

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    The first chapter of this part describes briefly the DOE policy for fusion energy. Subsequent chapters include: FY 1980 overview - activities of the Office of Fusion Energy; subactivity descriptions (confinement systems, development and technology, applied plasma physics, and reactor projects); field activities (DOE laboratories, educational institutions, nonprofit organizations, and commercial firms); commercialization; environmental implications; regional activities; and international programs

  6. Speech parts as Poisson processes.

    Science.gov (United States)

    Badalamenti, A F

    2001-09-01

    This paper presents evidence that six of the seven parts of speech occur in written text as Poisson processes, simple or recurring. The six major parts are nouns, verbs, adjectives, adverbs, prepositions, and conjunctions, with the interjection occurring too infrequently to support a model. The data consist of more than the first 5000 words of works by four major authors coded to label the parts of speech, as well as periods (sentence terminators). Sentence length is measured via the period and found to be normally distributed with no stochastic model identified for its occurrence. The models for all six speech parts but the noun significantly distinguish some pairs of authors and likewise for the joint use of all words types. Any one author is significantly distinguished from any other by at least one word type and sentence length very significantly distinguishes each from all others. The variety of word type use, measured by Shannon entropy, builds to about 90% of its maximum possible value. The rate constants for nouns are close to the fractions of maximum entropy achieved. This finding together with the stochastic models and the relations among them suggest that the noun may be a primitive organizer of written text.

  7. Virtual Parts Engineering Research Center

    Science.gov (United States)

    2010-05-20

    engineering 10 materials. High strength alloys , composites (polymer composites and metallic composites), and the like cannot merely be replaced by...ceramics, smart materials, shape memory alloys , super plastic materials and nano- structured materials may be more appropriate substitutes in a reverse...molding process using thermosetting Bakelite. For remanufacturing the part in small quantities, machining has been identified as the most economical

  8. Maintaining Healthy Skin -- Part 2

    Science.gov (United States)

    ... and SCI • Depression and SCI • Taking Care of Pressure Sores • Maintaining Healthy Skin (Part I) • Maintaining Healthy Skin ( ... For information on establishing skin tolerance, see our “Pressure Sores” pamphlet.) Pressure releases in a wheelchair can be ...

  9. Geometric design of part feeders

    NARCIS (Netherlands)

    Berretty, R.-P.M.

    2000-01-01

    This thesis presents solutions for problems derived from industrial assembly and robotic manipulation. The basic tasks in a factory are manufacturing the parts, and combining them into the desired product. In automating these tasks, we want to use robot manipulators that require little or no

  10. Mosquito Control: Do Your Part

    Centers for Disease Control (CDC) Podcasts

    Everyone can do their part to help control mosquitoes that can carry viruses like West Nile, Zika, dengue and chikungunya. In each episode of this podcast, you will learn ways to help reduce the number of mosquitoes in and around your home.

  11. Improved Radiography Of Wooden Parts

    Science.gov (United States)

    Berry, Maggie L.; Berry, Robert F., Jr.

    1990-01-01

    Technique developed to increase radiographic contrasts of inherent latent defects in wood. Involves introduction of radiopaque substance into defect site and subjecting site to penetrating radiation. Radiopaque penetrant used is commercially available fluorocarbon cleaning solvent, trichlorotrifluoroethane. Applicable in inspection of wooden aircraft components, fan and wind-turbine blades, marine parts, insulators, and other wooden components, assemblies, and structures.

  12. Hydroforming of flanged tubular part

    International Nuclear Information System (INIS)

    Joo, B. D.; Jang, J. H.; Choi, M. K.; Moon, Y. H.

    2010-01-01

    Tube hydroforming is the technology that utilizes hydraulic pressure to form a tube into desired shapes inside die cavities. Recently, tube hydroforming technology draws attentions of automotive industries due to its advantages such as weight reduction, increased strength, improved quality and reduced tooling cost. Hydroformed automotive parts used as structural components in vehicle body frame or subframe often have to be structurally joined at some point. Therefore it is useful if the hydroformed automotive parts can be given a localized attachment flange. In this study, a tube hydroformed product which has flange has been formed at various processing conditions. To accomplish successful flange hydroforming process, thorough investigation on proper combination of process parameters such as internal hydraulic pressure and tool geometry has been performed. For the process design FE analysis was performed with Dynaform 5.5. With optimized die parting angle and circumferential expansion ratio, hydroforming experiments to form flange were performed and forming characteristics at various process conditions were analyzed. The results show that flanged parts can be successfully produced by tube hydroforming process.

  13. Roots/Routes: Part II

    Science.gov (United States)

    Swanson, Dalene M.

    2009-01-01

    This narrative acts as an articulation of a journey of many routes. Following Part I of the same research journey of rootedness/routedness, it debates the nature of transformation and transcendence beyond personal and political paradoxes informed by neoliberalism and related repressive globalizing discourses. Through a more personal, descriptive,…

  14. Machine Shop Fundamentals: Part I.

    Science.gov (United States)

    Kelly, Michael G.; And Others

    These instructional materials were developed and designed for secondary and adult limited English proficient students enrolled in machine tool technology courses. Part 1 includes 24 lessons covering introduction, safety and shop rules, basic machine tools, basic machine operations, measurement, basic blueprint reading, layout, and bench tools.…

  15. Antifungal susceptibility testing of yeast isolated from corneal infections Teste de susceptibilidade a antifúngicos de leveduras isoladas de infecções corneais

    Directory of Open Access Journals (Sweden)

    Vera Lucia Degaspare Monte Mascaro

    2003-10-01

    Full Text Available PURPOSE: To report the antifungal susceptibility profile of yeast isolates obtained from cases of keratitis. METHODS: Susceptibility testing of 15 yeast strains isolated from corneal infections to amphotericin B, fluconazole, itraconazole and ketoconazole was performed using the NCCLS broth microdilution assay. RESULTS: Most episodes of eye infections were caused by Candida albicans. The antifungal drugs tested showed the following minimal inhibitory concentration values against yeast isolates: 0.125-0.5 µg/ml for amphotericin B; 0.125->64.0 µg/ml for fluconazole; 0.015-1.0 µg/ml for itraconazole and 0.015-0.125 µg/ml for ketoconazole. Despite the fact that all Candida isolates were judged to be susceptible to azoles, one isolate showed a minimal inhibitory concentration value significantly higher than a 90% minimal inhibitory concentration of all tested isolates. Rhodotorula rubra was resistant to fluconazole and itraconazole. CONCLUSIONS: Despite the fact that most yeast isolates from corneal infections are usually susceptible to amphotericin B and azoles, they exhibit a wide range of minimal inhibitory concentration values for antifungal drugs. The identification of strains at species level and their susceptibility pattern to antifungal drugs should be considered before determining the concentration to be used in topical antifungal formulations in order to optimize therapeutic response in eye infections.OBJETIVO: Relatar resultados e avaliar a aplicabilidade do teste de suscetibilidade a antifúngicos de leveduras isoladas de infecções corneais oculares. MÉTODOS: Realizou-se teste de suscetibilidade pelo método de microdiluição em caldo, padronizado pelo NCCLS-EUA, em 15 amostras de leveduras de infecções corneanas a anfotericina B, fluconazol, itraconazol e ketoconazol. RESULTADOS: A maioria dos episódios de infecção corneal foi causada por Candida albicans. As drogas antifúngicas testadas exibiram valores de concentra

  16. Rhodotorula minuta as onychomycosis agent in a Chinese patient: first report and literature review.

    Science.gov (United States)

    Zhou, Jie; Chen, Min; Chen, Hongduo; Pan, Weihua; Liao, Wanqing

    2014-03-01

    Onychomycosis is a common superficial fungal infection, which usually caused by dermatophytes, yeast and non-dermatophytic moulds. Recently, we isolated a Rhodotorula minuta isolate from a 15-year-old immunocompetent girl student in Hangzhou (China) that was identified using microscopy, culture morphology, histological diagnosis, API 20C AUX Yeast Identification Kit and sequencing of the Internal Transcribed Spacer region. In vitro, antifungal susceptibility tests showed that this yeast isolate was susceptible to low concentrations of amphotericin B, itraconazole, voriconazole and 5-flvoriconaz but that it appeared to be dose-dependent susceptible to fluconazole(MIC = 16 μg/ml). Furthermore, the effective result of therapy with itraconazole against R. minuta was consistent with that of susceptibility tests. © 2013 Blackwell Verlag GmbH.

  17. Automobile parts by radiation crosslinking

    International Nuclear Information System (INIS)

    Yoshii, Fumio

    2008-01-01

    Radiation crosslinking, graft polymerization and degradation are useful technologies to improve polymer materials. The crosslinking causes improvement in strength, heat stability and processability to gives network structure for polymer materials and hence crosslinked materials are used in various fields, especially car parts. Electron beam (EB) of short time irradiation is used for these modifications. Irradiated (pre-vulcanized) before sulfur vulcanization rubber tires, heat resistant wires/cables, shrinkable tubes and foams of car parts are achieved by EB crosslinking. Polyethylene and polyvinyl chloride are used in cables and wires, polypropylene in plastic foams and natural rubber etc. In this paper radiation processing of tire, wire/cables, foams, shrinkable tubes and circuit protection devices (CPT) are explained. (author)

  18. The Inconvenient Truth. Part 2

    International Nuclear Information System (INIS)

    Athanasiou, T.

    2007-01-01

    Essay-type of publication on what should happen next after Al Gore's presentations on the Inconvenient Truth about the impacts of climate change. The essay states in the first lines: 'We've seen the movie, so we know the first part - we're in trouble deep. And it's time, past time, for at least some of us to go beyond warning to planning, to start talking seriously about a global crash program to stabilize the climate

  19. Workshop 97. Part I. Proceedings

    International Nuclear Information System (INIS)

    1996-12-01

    The complete Proceedings, in 4 volumes, contain contributions by staff members of the Czech Technical University in Prague, the Technical University in Brno, and the Technical University (former University of Mining) in Ostrava, covering all branches of science and technology dealt with by the 3 universities. Part I includes contributions in mathematics, physics, engineering informatics and cybernetics, and computers. Out of these, 13 have been input to INIS. (P.A.)

  20. Workshop 97. Part I. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    The complete Proceedings, in 4 volumes, contain contributions by staff members of the Czech Technical University in Prague, the Technical University in Brno, and the Technical University (former University of Mining) in Ostrava, covering all branches of science and technology dealt with by the 3 universities. Part I includes contributions in mathematics, physics, engineering informatics and cybernetics, and computers. Out of these, 13 have been input to INIS. (P.A.).

  1. Risk of serious skin disorders among users of oral antifungals: a population-based study

    Directory of Open Access Journals (Sweden)

    Duque Alberto

    2002-11-01

    Full Text Available Abstract Background Serious skin disorders have been associated with the use of oral antifungals in a number of case reports and series of cases. However the incidence of these disorders remains unknown. Methods We estimated the risk of serious skin disorders in a cohort of users of oral antifungals identified in the general population of the General Practice Research Database in the UK. The cohort included 61,858 patients, 20 to 79 years old, who had received at least one prescription for either oral fluconazole, griseofulvin, itraconazole, ketoconazole, or terbinafine. Results The background rate of serious cutaneous adverse reactions (the one corresponding to non use of oral antifungals was 3.9 per 10,000 person-years (95% CI 2.9–5.2. Incidence rates for current use were 15.4 per 10,000 person-years (1.9–55.7 for itraconazole, 11.1 (3.0–28.5 for terbinafine, 10.4 (1.3–37.5 for fluconazole, and 4.6 (0.1–25.8 for griseofulvin. Itraconazole was the antifungal associated with the highest relative risk, 3.9 (0.5–15.0, when compared to the risk among non users, followed by terbinafine and fluconazole, with relative risks of 2.8 (0.7–7.8 and 2.6 (0.3–10.1, respectively. Conclusions We conclude that cutaneous disorders associated with the use of oral antifungals in this study were all of mild severity and that the risk associated with the use of oral antifungals was slightly higher than the risk in non-users. The safety profile of terbinafine regarding cutaneous disorders is similar to other antifungals and in the very low range of risks associated with other drugs.

  2. Comparison of in vitro activity of five antifungal agents against dermatophytes, using the agar dilution and broth microdilution methods Comparação da atividade in vitro de cinco agentes antifúngicos para dermatófitos, usando os métodos de diluição em ágar e microdiluição em caldo

    Directory of Open Access Journals (Sweden)

    Crystiane Rodrigues Araújo Mota

    2009-06-01

    Full Text Available The purpose of this study was to compare the agar dilution and broth microdilution methods for determining the minimum inhibitory concentration (MIC of fluconazole, itraconazole, ketoconazole, griseofulvin and terbinafine for 60 dermatophyte samples belonging to the species Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum canis. The percentage agreement between the two methods, for all the isolates with O propósito do presente trabalho foi comparar os métodos de diluição em ágar e diluição em caldo para a determinação de concentração inibitória mínima de fluconazol, itraconazol, cetoconazol, griseofulvina e terbinafina para 60 amostras de dermatófitos pertencentes às espécies, Trichophyton rubrum, Trichophyton. mentagrophytes e Microsporum canis. A porcentagem de acordo entre os dois métodos para todos os isolados testados considerando-se valores < 2 diluições, foram de 91,6% para cetoconazol e para griseofulvina, de 88,3% para itraconazol, de 81,6% para terbinafina e de 73,3% para fluconazol. Uma concordância de 100% foi obtido para isolados de Trichophyton mentagrophytes avaliados com cetoconazol e griseofulvina. Desta forma, até que um método de referência seja padronizado para testar a suscetibilidade in vitro para os dermatófitos, os resultados semelhantes encontrados para os dois métodos fazem com que o método de diluição em ágar possa ser útil no teste de suscetibilidade para estes fungos filamentosos.

  3. Nuclear medicine. 1 part. Manual

    International Nuclear Information System (INIS)

    Shlygina, O.E.; Borisenko, A.R.

    2006-01-01

    Current manual is urged to give wide-scale readers a submission on a key principles and methods of nuclear medicine, and it opportunities and restrictions in diagnostics and treatment of different diseases. Nuclear medicine is differing first of all by combination of diverse knowledge fields: special knowledge of a doctor, knowledge of physical processes bases, related with radiation, grounds of radiopharmaceutics, dosimetry. In the base of the book the 5th edition of 'Nuclear medicine' manual in 2 parts of German authors - Schicha, G.; Schober, O. is applied. In the book publishing the stuff of the Institute of Nuclear Physics of the National Nuclear Center of Republic of Kazakhstan has been worked. Modifications undergo practically all chapters: especially the second one, forth and sixth was enlarged. The 1 part of the book was published due to support of IAEA within the Technical cooperation project 'Implementation of Nuclear Medicine and Biophysics Center' (KAZ/6/007). The manual second part - devoted to applications of nuclear medicine methods for diagnostics and treatment - will be published in 2007

  4. Smart variations: Functional substructures for part compatibility

    KAUST Repository

    Zheng, Youyi; Cohen-Or, Daniel; Mitra, Niloy J.

    2013-01-01

    As collections of 3D models continue to grow, reusing model parts allows generation of novel model variations. Naïvely swapping parts across models, however, leads to implausible results, especially when mixing parts across different model families

  5. In vitro susceptibility testing of dermatophytes isolated in Goiania, Brazil, against five antifungal agents by broth microdilution method Teste de suscetibilidade in vitro de dermatófitos isolados em Goiânia, Brasil, contra cinco agentes antifúngicos pelo método de microdiluição em caldo

    Directory of Open Access Journals (Sweden)

    Crystiane Rodrigues Araújo

    2009-02-01

    Full Text Available The antifungal activities of fluconazole, itraconazole, ketoconazole, terbinafine and griseofulvin were tested by broth microdilution technique, against 60 dermatophytes isolated from nail or skin specimens from Goiania city patients, Brazil. In this study, the microtiter plates were incubated at 28 ºC allowing a reading of the minimal inhibitory concentration (MIC after four days of incubation for Trichophyton mentagrophytes and five days for T. rubrum and Microsporum canis. Most of the dermatophytes had uniform patterns of susceptibility to the antifungal agents tested. Low MIC values as 0.03 µg/mL were found for 33.3%, 31.6% and 15% of isolates for itraconazole, ketoconazole and terbinafine, respectively.Atividades antifúngicas de fluconazol, itraconazol, cetoconazol, terbinafina e griseofulvina foram testadas pelo método de microdiluição em caldo contra 60 isolados de dermatófitos. Os resultados mostraram que todos os isolados produziram crescimento claramente detectável a 28 ºC e a concentração inibitória mínima (CIM foi determinada após quatro dias de incubação para Trichophyton mentagrophytes e cinco dias para T. rubrum e Microsporum canis. A maioria dos isolados teve um padrão uniforme de suscetibilidade para os agentes antifúngicos testados. Baixos valores de CIM como 0,03 µg/mL foram encontrados para 33,3%, 31,6% e 15% dos isolados para itraconazol, cetoconazol e terbinafina, respectivamente.

  6. Sporotrichosis in Renal Transplant Patients

    Directory of Open Access Journals (Sweden)

    Paulo Gewehr

    2013-01-01

    Full Text Available The current report describes two renal transplant recipients who presented with sporotrichosis. In addition, the authors review the general aspects of sporotrichosis in renal transplant recipients reported in the literature. Sporotrichosis is a rare fungal infection in transplant patients and has been reported primarily in renal transplant recipients not treated with antifungal prophylaxis. Extracutaneous forms of sporotrichosis without skin manifestations and no previous history of traumatic injuries have been described in such patients and are difficult to diagnose. Renal transplant recipients with sporotrichosis described in the present report were successfully treated with antifungal therapy including amphotericin B deoxycholate, lipid amphotericin B formulations, fluconazole and itraconazole.

  7. Disseminated phaeohyphomycosis in a dog

    Directory of Open Access Journals (Sweden)

    Lana S. Rothenburg

    2017-03-01

    Full Text Available Phaeohyphomycosis is a rare but emerging disease caused by dematiaceous fungi. Here we describe the case of an immunosuppressed dog with disseminated phaeohyphomycosis secondary to Bipolaris spicifera infection. Regionally extensive infiltration of the paw pads, skin, myocardium, liver, renal interstitium and diaphragm was identified on histopathology. Candida glabrata and Fusarium oxysporum were also cultured from multiple sites post-mortem. The dog was treated with fluconazole, itraconazole, terbinafine and liposomal amphotericin B, but was euthanized due to its poor prognosis after 12 days of therapy.

  8. Drug resistance of yeasts isolated from oropharyngeal candidiasis in aids patients Resistência à drogas de leveduras isoladas de candidíase orofaríngea em pacientes com Aids

    Directory of Open Access Journals (Sweden)

    Maria do Rosário Rodrigues Silva

    1998-10-01

    Full Text Available Candida spp was isolated from 59 (68.60% out of eighty six samples of oral mucosa of AIDS patients. The identification, based or the production of a germ tube and chlamydospores, and on the assimilation and fermentation of carbohydrates, revealed 52 strains (88.13% of C. albicans, 4 (6.77% of C. tropicalis and 3 (5.08% of C. krusei. The susceptibility of these strains to amphotericin B, flucytosine, itraconazole, fluconazole and ketoconazole was determined using the agar dilution method. Comparing the minimum inhibitory concentration values found in the susceptibility test with the serum levels achieved by these drugs, only 8.47% and 5.08% of the yeasts strains proved to be resistant to amphotericin B and flucitosyne, respectively. A high frequency of strains resistant to azole derivatives (25.42%, to itraconazole, 45.76%, to ketoconazole and 66.10% to fluconazole was observed.Entre oitenta e seis amostras da mucosa oral de pacientes com AIDS, 59 (68,60% foram positivas para leveduras do gênero Candida. A identificação, feita pela produção de tubo germinativo e clamidósporos e através de assimilação e fermentação de hidratos de carbono, revelou 52 cepas (88,13% de C.albicans, 4 (6,77% de C. tropicalis e 3 (5,08% de C.krusei. Avaliação destas leveduras para susceptibilidade in vitro frente a anfotericina B, flucitosina, itraconazol, fluconazol e cetoconazol, foi realizada pelo método de diluição em ágar. Comparando-se os valores de concentração inibitória mínima encontrados com os níveis séricos alcançados por estes antifúngicos verificou-se que apenas 8,47% e 5,08% das 59 leveduras foram resistentes a anfotericina B e flucitosina, respectivamente. Foi registrada uma percentagem de cepas resistentes aos derivados azólicos, sendo 25,42% ao itraconazol, 45,76% ao cetoconazol e 66,10% ao fluconazol.

  9. Candidaemia and antifungal susceptibility testing in a teaching hospital.

    Science.gov (United States)

    Tzar, M N; Shamim, A S

    2009-03-01

    We reviewed cases of candidaemia at Universiti Kebangsaan Malaysia Medical Centre from 1st January 2005 to 30th June 2006. All blood cultures positive for Candida species or its teleomorphs within the study period were identified and antifungal susceptibility testing was performed. Out of 50 blood isolates, 20 (40%) were identified as Candida albicans, 16 (32%) C. tropicalis, five (10%) C. parapsilosis, three (6%) C. famata, two (4%) C. glabrata, two (4%) Pichia ohmeri, one (2%) C. krusei and one (2%) P. etchell/carsonii. Susceptibility to amphotericin B was 100%, fluconazole 90%, itraconazole 40%, ketoconazole 88%, 5-flucytosine 98% and voriconazole 98%.

  10. Conazoles

    Directory of Open Access Journals (Sweden)

    Jan Heeres

    2010-06-01

    Full Text Available This review provides a historical overview of the analog based drug discovery of miconazole and its congeners, and is focused on marketed azole antifungals bearing the generic suffix “conazole”. The antifungal activity of miconazole, one of the first broad-spectrum antimycotic agents has been mainly restricted to topical applications. The attractive in vitro antifungal spectrum was a starting point to design more potent and especially orally active antifungal agents such as ketoconazole, itraconazole, posaconazole, fluconazole and voriconazole. The chemistry, in vitro and in vivo antifungal activity, pharmacology, and clinical applications of these marketed conazoles has been described.

  11. Unconventional material part FEM analysis

    Directory of Open Access Journals (Sweden)

    Michal TROPP

    2016-12-01

    Full Text Available The article covers the usability of alternative materials in vehicles construction. The paper elaborates upon the setup of the process and analysis of the results of carbon composite component FEM model. The 3D model, used for the examination, is a part of axle from alternative small electric vehicle. The analysis was conducted with the help of MSC Adams and Ansys Workbench software. Color maps of von Mises stress in material and total deformations of the component are the results of calculation.

  12. Part time secretarial assistant needed

    CERN Multimedia

    2004-01-01

    The English National Programme at the Lycée International, Ferney-Voltaire, one of the Programmes originally set up by CERN to provide schooling for children of Members of the Personnel in their maternal language, is recruiting a part time secretarial assistant. Applications for this post should be sent as soon as possible. The closing date is the end of the day on July 19th. Applicants will find details on the ‘Staff Vacancies' page of our website: http://enpferney.org/

  13. The Sum of the Parts

    DEFF Research Database (Denmark)

    Gross, Fridolin; Green, Sara

    2017-01-01

    Systems biologists often distance themselves from reductionist approaches and formulate their aim as understanding living systems “as a whole”. Yet, it is often unclear what kind of reductionism they have in mind, and in what sense their methodologies offer a more comprehensive approach. To addre......-up”. Specifically, we point out that system-level properties constrain lower-scale processes. Thus, large-scale modeling reveals how living systems at the ​same time ​ are ​more and ​less than the sum of the parts....

  14. Standards in neurosonology. Part I

    Directory of Open Access Journals (Sweden)

    Joanna Wojcza

    2015-09-01

    Full Text Available The paper presents standards related to ultrasound imaging of the cerebral vasculature and structures. The aim of this paper is to standardize both the performance and description of ultrasound imaging of the extracranial and intracranial cerebral arteries as well as a study of a specifi c brain structure, i.e. substantia nigra hyperechogenicity. The following aspects are included in the description of standards for each ultrasonographic method: equipment requirements, patient preparation, study technique and documentation as well as the required elements of ultrasound description. Practical criteria for the diagnosis of certain pathologies in accordance with the latest literature were also presented. Furthermore, additional comments were included in some of the sections. Part I discusses standards for the performance, documentation and description of different ultrasound methods (Duplex, Doppler. Part II and III are devoted to standards for specifi c clinical situations (vasospasm, monitoring after the acute stage of stroke, detection of a right-toleft shunts, confi rmation of the arrest of the cerebral circulation, an assessment of the functional effi ciency of circle of Willis, an assessment of the cerebrovascular vasomotor reserve as well as the measurement of substantia nigra hyperechogenicity.

  15. Standards in neurosonology. Part III

    Directory of Open Access Journals (Sweden)

    Joanna Wojczal

    2016-06-01

    Full Text Available The paper presents standards related to ultrasound imaging of the cerebral vasculature and structures. The aim of this paper is to standardize both the performance and description of ultrasound imaging of the extracranial and intracranial cerebral arteries as well as a study of a specific brain structure, i.e. substantia nigra hyperechogenicity. The following aspects are included in the description of standards for each ultrasonographic method: equipment requirements, patient preparation, study technique and documentation as well as the required elements of ultrasound description. Practical criteria for the diagnosis of certain pathologies in accordance with the latest literature were also presented. Furthermore, additional comments were included in some of the sections. Part I discusses standards for the performance, documentation and description of different ultrasound methods (Duplex, Doppler. Part II and III are devoted to standards for specific clinical situations (vasospasm, monitoring after the acute stage of stroke, detection of a right-to-left shunts, confirmation of the arrest of the cerebral circulation, an assessment of the functional efficiency of circle of Willis, an assessment of the cerebrovascular vasomotor reserve as well as the measurement of substantia nigra hyperechogenicity.

  16. The Effects of Antifungal Azoles on Inflammatory Cytokine Production in Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    K Zomorodian

    2008-04-01

    Full Text Available ABSTRACT: Introduction & Objective: Azoles drugs are being used successfully in treatment of fungal infections. Recently, immunosuppressive effects of some of these agents have been reported. Keratinocytes, as the major cells of the skin, have an important role in innate immunity against pathogenic agents. Considering the scanty of information about the effects of azoles on immune responces, this study was conducted to assess the expression and secretion of inflammatory cytokines in keratinocytes following treatment with azole drugs. Materials & Methods: This is an exprimental study conducted in in molecular biology division in Tehran University of Medical Sciences and Immunodermatology Department in Vienna Medical University. Primery keratinocytes were cultured and treated with different concentrations of fluconazole, itraconazole, ketoconazole and griseofulvin. Secreted IL1, IL6 and TNF-α by keratinocytes in culture supernatant were measured by quantitative enzyme immunoassay technique. Moreover, expression of the genes encoding IL1 and IL8 was evaluated by Real Time-PCR. Results: Treatment of keratinocytes with different concentrations of fluconazole and low concentration of ketoconazole resulted in decrease in IL1 secretion, but Itraconazole and griseofulvin did not show such an effect at the same concentrations. In addition, none of the examined drugs had an effect on secretion level of IL6 and TNF-α. Quantitative analysis of IL1 and IL8 encoding genes revealed that transcription on these genes might be suppressed following treatment with fluconazole or ketoconazole. Conclusion: Fluconazole and ketoconazole might modulate the expression and secretion of IL1 and IL8 and affect the direction of immune responses induced by keratinocytes

  17. Antifungal Susceptibilities of Candida Species Causing Vulvovaginitis and Epidemiology of Recurrent Cases

    Science.gov (United States)

    Richter, Sandra S.; Galask, Rudolph P.; Messer, Shawn A.; Hollis, Richard J.; Diekema, Daniel J.; Pfaller, Michael A.

    2005-01-01

    There are limited data regarding the antifungal susceptibility of yeast causing vulvovaginal candidiasis, since cultures are rarely performed. Susceptibility testing was performed on vaginal yeast isolates collected from January 1998 to March 2001 from 429 patients with suspected vulvovaginal candidiasis. The charts of 84 patients with multiple positive cultures were reviewed. The 593 yeast isolates were Candida albicans (n = 420), Candida glabrata (n = 112), Candida parapsilosis (n = 30), Candida krusei (n = 12), Saccharomyces cerevisiae ( n = 9), Candida tropicalis (n = 8), Candida lusitaniae (n = 1), and Trichosporon sp. (n = 1). Multiple species suggesting mixed infection were isolated from 27 cultures. Resistance to fluconazole and flucytosine was observed infrequently (3.7% and 3.0%); 16.2% of isolates were resistant to itraconazole (MIC ≥ 1 μg/ml). The four imidazoles (econazole, clotrimazole, miconazole, and ketoconazole) were active: 94.3 to 98.5% were susceptible at ≤1 μg/ml. Among different species, elevated fluconazole MICs (≥16 μg/ml) were only observed in C. glabrata (15.2% resistant [R], 51.8% susceptible-dose dependent [S-DD]), C. parapsilosis (3.3% S-DD), S. cerevisiae (11.1% S-DD), and C. krusei (50% S-DD, 41.7% R, considered intrinsically fluconazole resistant). Resistance to itraconazole was observed among C. glabrata (74.1%), C. krusei (58.3%), S. cerevisiae (55.6%), and C. parapsilosis (3.4%). Among 84 patients with recurrent episodes, non-albicans species were more common (42% versus 20%). A ≥4-fold rise in fluconazole MIC was observed in only one patient with C. parapsilosis. These results support the use of azoles for empirical therapy of uncomplicated candidal vulvovaginitis. Recurrent episodes are more often caused by non-albicans species, for which azole agents are less likely to be effective. PMID:15872235

  18. In vitro susceptibility of Candida albicans clinical isolates to eight antifungal agents in Ouagadougou (Burkina Faso).

    Science.gov (United States)

    Zida, A; Yacouba, A; Bamba, S; Sangare, I; Sawadogo, M; Guiguemde, T; Kone, S; Traore, L K; Ouedraogo-Traore, R; Guiguemde, R T

    2017-12-01

    In recent years, the infection Candida albicans infection worldwide has risen, and the incidence of resistance to traditional antifungal therapies is also increasing. The aim of this study was to evaluate in vitro susceptibility of C. albicans clinical isolates to eight antifungal agents in Ouagadougou. A cross-sectional study was conducted from January 2013 to December 2015 at Yalgado Ouédraogo University Teaching Hospital. Two hundred seven strains have been isolated from 347 symptomatic patients received in different clinical services. Samples were cultured on Sabouraud Dextrose Agar supplemented with Cloramphenicol. Isolates were diagnosed as C. albicans using germ tube test, chlamydospore formation on Corn Meal Agar, and Api-Candida test (Biomérieux). Antifungal susceptibility testing was performed by disk diffusion method and isolates classified as susceptible, susceptible dose-dependent and resistant. Three hundred forty-seven (347) patients are included in this study. Two hundred and six (206) out of 347 collected samples (59.36%) were found positive for C. albicans. The strains were mostly isolated from vulvovaginal (49%) and oral infections (40.3%). The highest resistance rates of azoles were obtained with fluconazole (66.5%), itraconazole (52.3%) and ketoconazole (22.9%) when all clinical isolates were included. The resistance rates of fluconazole, itraconazole and ketoconazole remain highest for vulvovaginal and oral isolates. The rate of resistance to the polyene amphotericin B was 32.0% for all clinical isolates and was 56.4% for vulvovaginal strains. Resistance rate to nystatin was 6.3% for all clinical isolates. Cross-resistance analysis with data of all clinical strains revealed that the incidence of resistance to ketoconazole and itraconazole in fluconazole-resistant isolates was significantly higher than recorded for fluconazole-susceptible isolates. In vitro C. albicans antifungal susceptibility test in this study showed relatively high

  19. Advances in photovoltaics part 4

    CERN Document Server

    Willeke, Gerhard P

    2015-01-01

    Advances in Photovoltaics: Part Four provides valuable information on the challenges faced during the transformation of our energy supply system to more efficient, renewable energies. The volume discusses the topic from a global perspective, presenting the latest information on photovoltaics, a cornerstone technology. It covers all aspects of this important semiconductor technology, reflecting on the tremendous and dynamic advances that have been made on this topic since 1975, when the first book on solar cells-written by Harold J. Hovel of IBM-was published as volume 11 in the now famous series on Semiconductors and Semimetals. Readers will gain a behind the scenes look at the continuous and rapid scientific development that leads to the necessary price and cost reductions in global industrial mass-production. Written by leading, internationally known experts on his topic Provides an in-depth overview of the current status and perspectives of thin film PV technologies Discusses the challenges faced during th...

  20. Forming parts over small radii

    International Nuclear Information System (INIS)

    Hazra, S K; Hughes, D J; Pereira, M P; Rolfe, B F

    2016-01-01

    Stamping simulations usually make the plane stress simplifying assumption. However, this becomes less valid when material draws around features with radius to sheet thickness ratios less than 20. Pereira, Yan and Rolfe (Wear, Vol.265, p.1687 (2008)) predicted that out-of-plane stress equivalent to material yield can occur because a line contact forms briefly at the start of the draw process. The high transient stress can cause high rates of tool wear and may cause the ‘die impact line’ cosmetic defect. In this work, we present residual strain results of a channel section that was drawn over a small radius. Using the neutron source at the Institut Laue-Langevin, in-plane and out-of-plane strains were measured in the channel part to show some support for the conclusions of Pereira et. al. (paper)

  1. Room for Sustainable Agriculture. Part 1 Advice. Part 2 Analysis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-03-15

    An outline is given of the social dilemmas associated with agriculture and horticulture in the Netherlands. Ongoing innovation and accelerated sustainable development are essential to resolve these dilemmas. Given the importance of the Dutch agriculture and horticulture sector, there is every reason for the central government to play its part and help remove the obstacles to the continuing sustainable development of the sector. The Council recommends that the central government continues developing the Council's vision for agriculture and horticulture with the parties concerned, allows scope for the development of different agricultural business models, applies knowledge and innovation as drivers of continuing sustainable development, amends laws and regulations as necessary, and facilitates a permanent dialogue between the sector and society. The advisory report also sets out the Council's vision concerning the political and public debate on agriculture and horticulture. This debate is most clearly characterised by major and seemingly insurmountable differences of opinion. The Council hopes that its report will induce a shift in thinking about Dutch agriculture among politicians and society at large, so that the transitions considered necessary by the Council can be implemented more rapidly.

  2. Room for Sustainable Agriculture. Part 1 Advice. Part 2 Analysis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-03-15

    An outline is given of the social dilemmas associated with agriculture and horticulture in the Netherlands. Ongoing innovation and accelerated sustainable development are essential to resolve these dilemmas. Given the importance of the Dutch agriculture and horticulture sector, there is every reason for the central government to play its part and help remove the obstacles to the continuing sustainable development of the sector. The Council recommends that the central government continues developing the Council's vision for agriculture and horticulture with the parties concerned, allows scope for the development of different agricultural business models, applies knowledge and innovation as drivers of continuing sustainable development, amends laws and regulations as necessary, and facilitates a permanent dialogue between the sector and society. The advisory report also sets out the Council's vision concerning the political and public debate on agriculture and horticulture. This debate is most clearly characterised by major and seemingly insurmountable differences of opinion. The Council hopes that its report will induce a shift in thinking about Dutch agriculture among politicians and society at large, so that the transitions considered necessary by the Council can be implemented more rapidly.

  3. Atmospheric fluoride pollution. Part II

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, T; Yamazaki, Y

    1969-01-01

    In East Osaka, agricultural crops either died or showed poor growth in the neighborhood of a factory producing white cosmetic bottles. Since fluorite was used as a material and there was no damage before the establishment of the factory, it was suspected that fluorine compounds were causing the damage. Quantitative analysis was performed on the agricultural crops and the exhaust gas as well as the dust particles in order to determine the fluorine content. Gas samplers were used to collect the dusts from the surrounding atmosphere. The fluorine content of dust near the factory was about 93 mg per cubic meter per day, and in some parts, as high as 1.54 mq per cubic meter per day. Relatively larger quantities of fluorine were measured at the southwestern and southeastern area of the factory, corresponding to the general wind pattern. Rice and soy beans from the neighborhood of the factory showed concentrations of fluorine and, especially in the leaves of the damaged crops, the concentrations were several hundred times higher than those of the undamaged leaves.

  4. Intrauterine growth restriction - part 2.

    Science.gov (United States)

    Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

    2016-12-01

    Small for gestational age (SGA) infants have been classically defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age, whereas intrauterine growth restriction (IUGR) has been defined as a rate of foetal growth that is less than normal for the population and for the growth potential of a specific infant. SGA infants have more frequent problems such as perinatal asphyxia, hypothermia, hypoglycaemia, polycythaemia and many more when compared with their appropriate for gestational age counterpart. They too have growth retardation and various major and subtle neurodevelopmental handicaps, with higher rates of perinatal and neonatal mortality. With the advent of newer technologies, even though the perinatal diagnosis of these SGA/IUGR foetuses has increased, but still perinatal morbidity and mortality rates are higher than normal foetuses and infants. In this part, we have covered neonatal IUGR classification, postnatal diagnosis, short-term and long-term complications faced by these IUGR infants.

  5. What is WHMIS? Part One

    Energy Technology Data Exchange (ETDEWEB)

    Matthew, M. A.

    2003-07-01

    Essential features of the Workplace Hazardous Materials Information System (WHMIS) are outlined. WHMIS was introduced by the federal government in 1988, followed in quick succession by specific regulations by the provinces and territories. The WHMIS regulations set out what an employer must do to comply to ensure that controlled products are used, handled, and/or disposed of in the workplace are labelled, that employees are fully trained on the safe use, handling, storage and disposal of all controlled products, and that a material safety data sheet (MSDS) that describes each product is available on site for employees. The controlled products regulation (CPR) which is separate from the WHMIS regulations sets the specific requirements for product labelling for suppliers and importers. Controlled products are categorized in four classes and various subclasses, such as flammable/combustible materials, oxidizing materials, materials of immediate and serious toxic effects, corrosive materials, etc. Part Two of this article will explain supplier versus workplace labels, the content of the material data sheets and will provide details about employee training methods.

  6. Commercial Parts Technology Qualification Processes

    Science.gov (United States)

    Cooper, Mark S.

    2013-01-01

    Many high-reliability systems, including space systems, use selected commercial parts (including Plastic Encapsulated Microelectronics or PEMs) for unique functionality, small size, low weight, high mechanical shock resistance, and other factors. Predominantly this usage is subjected to certain 100% tests (typically called screens) and certain destructive tests usually (but not always) performed on the flight lot (typically called qualification tests). Frequently used approaches include those documented in EEE-INST-002 and JPL DocID62212 (which are sometimes modified by the particular aerospace space systems manufacturer). In this study, approaches from these documents and several space systems manufacturers are compared to approaches from a launch systems manufacturer (SpaceX), an implantable medical electronics manufacturer (Medtronics), and a high-reliability transport system process (automotive systems). In the conclusions section, these processes are outlined for all of these cases and presented in tabular form. Then some simple comparisons are made. In this introduction section, the PEM technology qualification process is described, as documented in EEE-INST-002 (written by the Goddard Space Flight Center, GSFC), as well as the somewhat modified approach employed at the Jet Propulsion Laboratory (JPL). Approaches used at several major NASA contractors are also described

  7. Drilling miniature holes, Part III

    Energy Technology Data Exchange (ETDEWEB)

    Gillespie, L.K.

    1978-07-01

    Miniature components for precision electromechanical mechanisms such as switches, timers, and actuators typically require a number of small holes. Because of the precision required, the workpiece materials, and the geometry of the parts, most of these holes must be produced by conventional drilling techniques. The use of such techniques is tedious and often requires considerable trial and error to prevent drill breakage, minimize hole mislocation and variations in hole diameter. This study of eight commercial drill designs revealed that printed circuit board drills produced better locational and size repeatability than did other drills when centerdrilling was not used. Boring holes 1 mm in dia, or less, as a general rule did not improve hole location in brass or stainless steel. Hole locations of patterns of 0.66-mm holes can be maintained within 25.4-..mu..m diametral positional tolerance if setup misalignments can be eliminated. Size tolerances of +- 3.8 ..mu..m can be maintained under some conditions when drilling flat plates. While these levels of precision are possible with existing off-the-shelf drills, they may not be practical in many cases.

  8. TSUNAMI INFORMATION SOURCES PART 2

    Directory of Open Access Journals (Sweden)

    Robert L. Wiegel

    2006-01-01

    Full Text Available Tsunami Information Sources (Robert L. Wiegel, University of California, Berkeley, CA, UCB/HEL 2005-1, 14 December 2005, 115 pages, is available in printed format, and on a diskette. It is also available in electronic format at the Water Resources Center Archives, University of California, Berkeley, CA http:www.lib.berkeley.edu/WRCA/tsunamis.htmland in the International Journal of The Tsunami Society, Science of Tsunami Hazards (Vol. 24, No. 2, 2006, pp 58-171 at http://www.sthjournal.org/sth6.htm.This is Part 2 of the report. It has two components. They are: 1.(Sections A and B. Sources added since the first report, and corrections to a few listed in the first report. 2.(Sections C and D. References from both the first report and this report, listed in two categories:Section C. Planning and engineering design for tsunami mitigation/protection; adjustments to the hazard; damage to structures and infrastructureSection D. Tsunami propagation nearshore; induced oscillations; runup/inundation (flooding and drawdown.

  9. Part 1: diagnosis and monitoring

    Directory of Open Access Journals (Sweden)

    Dorota Krasowska

    2017-11-01

    Full Text Available Systemic sclerosis is an immune-mediated disease characterized by a chronic and progressive course. It often leads to multiorgan failure and patient disability, and contributes to significant reduction in the quality of life. Systemic sclerosis affects the skin, subcutaneous tissue, muscles, osteoarticular system and internal organs. The complexity and diversity of clinical presentations require an individual approach and multidisciplinary collaboration both at the stage of diagnosis and treatment. Critical factors in systemic sclerosis include early diagnosis, assessment of internal organ involvement, identification of patients at potential risk of organ complications, assessment of disease dynamics and activity, and implementation of optimal therapy. Part 1 presents current recommendations for the diagnostics and monitoring of patients with systemic sclerosis. Attention is given to classification criteria, clinical forms of systemic sclerosis, assessment of skin thickness and systemic sclerosis microangiopathy, significance of antinuclear antibodies, diagnosis of interstitial lung disease and pulmonary arterial hypertension, renal crisis and cardiac abnormalities, and evaluation of the gastrointestinal tract and osteoarticular and muscular systems.

  10. Pediatricians Working Part-Time Has Plateaued.

    Science.gov (United States)

    Cull, William L; Frintner, Mary Pat; O'Connor, Karen G; Olson, Lynn M

    2016-04-01

    To examine trends in pediatricians working part-time and residents seeking part-time work and to examine associated characteristics. The American Academy of Pediatrics (AAP) Periodic Survey of Fellows and the AAP Annual Survey of Graduating Residents were used to examine part-time employment. Fourteen periodic surveys were combined with an overall response rate of 57%. Part-time percentages were compared for surveys conducted from 2006-2009 and 2010-2013. The AAP Annual Surveys of Graduating Residents (combined response rate = 60%) from 2006-2009 were compared with 2010-2013 surveys for residents seeking and obtaining part-time positions following training. Multivariable logistic regression models identified characteristics associated with part-time work. Comparable percentages of pediatricians worked part-time in 2006-2009 (23%) and 2010-2013 (23%). There was similarly no statistically significant difference in residents seeking part-time work (30%-28%), and there was a slight decline in residents accepting part-time work (16%-13%, aOR .75, 95% CI .56-.96). Increases in working part-time were not found for any subgroups examined. Women consistently were more likely than men to work part-time (35% vs 9%), but they showed different patterns of part-time work across age. Women in their 40s (40%) were more likely than other women (33%) and men in their 60s (20%) were more likely than other men (5%) to work part-time. There has been a levelling off in the number of pediatricians working part-time and residents seeking part-time work. Overall, women remain more likely to work part-time, although 1 in 5 men over 60 work part-time. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Spare Parts Management of Aging Capital Products

    NARCIS (Netherlands)

    M. Hekimoğlu (Mustafa)

    2015-01-01

    textabstractSpare parts are critical for operations of capital products such as aircraft, refineries, trucks, etc/, which require maintenance regularly. Original Equipment Manufacturers (OEMs) bear the responsibility of undisrupted maintenance service and spare parts flow for their capital products.

  12. Automated visual inspection of moving custom parts

    CSIR Research Space (South Africa)

    Davrajh, S

    2008-01-01

    Full Text Available frequencies than batched produced parts. This higher frequency of inspection significantly impacts inspection times, and inherently, production rates. An effective, diverse, accurate, robust, and time efficient method for inspecting custom parts is therefore...

  13. 30 CFR 57.19122 - Replacement parts.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Replacement parts. 57.19122 Section 57.19122 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Inspection and Maintenance § 57.19122 Replacement parts. Parts used to repair hoists shall have properties...

  14. 30 CFR 56.19122 - Replacement parts.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Replacement parts. 56.19122 Section 56.19122 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Inspection and Maintenance § 56.19122 Replacement parts. Parts used to repair hoists shall have properties...

  15. Part-time jobs : What women want?

    NARCIS (Netherlands)

    Booth, A.L.; van Ours, J.C.

    2013-01-01

    Part-time jobs are common among partnered women in many countries. There are two opposing views on the efficiency implications of so many women working part-time. The negative view is that part-time jobs imply wastage of resources and underutilization of investments in human capital since many

  16. Part-time Jobs : What Women Want?

    NARCIS (Netherlands)

    Booth, A.L.; van Ours, J.C.

    2010-01-01

    Part-time jobs are popular among partnered women in many countries. In the Netherlands the majority of partnered working women have a part-time job. Our paper investigates, from a supply-side perspective, if the current situation of abundant part-time work in the Netherlands is likely to be a

  17. Parts, Cavities, and Object Representation in Infancy

    Science.gov (United States)

    Hayden, Angela; Bhatt, Ramesh S.; Kangas, Ashley; Zieber, Nicole

    2011-01-01

    Part representation is not only critical to object perception but also plays a key role in a number of basic visual cognition functions, such as figure-ground segregation, allocation of attention, and memory for shapes. Yet, virtually nothing is known about the development of part representation. If parts are fundamental components of object shape…

  18. Some Aspects of Part-Time Work.

    Science.gov (United States)

    Australian Dept. of Labour and National Service, Melbourne. Women's Bureau.

    Of major importance to many married women seeking employment in Australia is the availability of part-time work. To describe the economic aspects of part-time employment for women, a review was made of statistics published by the Commonwealth Bureau of Census and Statistics and of research on part-time employment in overseas countries, and a…

  19. NASA EEE Parts and NASA Electronic Parts and Packaging (NEPP) Program Update 2018

    Science.gov (United States)

    Label, Kenneth A.; Sampson, Michael J.; Pellish, Jonathan A.; Majewicz, Peter J.

    2018-01-01

    NASA Electronic Parts and Packaging (NEPP) Program and NASA Electronic Parts Assurance Group (NEPAG) are NASAs point-of-contacts for reliability and radiation tolerance of EEE parts and their packages. This presentation includes an FY18 program overview.

  20. Changing nature of equipment and parts qualification

    International Nuclear Information System (INIS)

    Bucci, R.M.

    1988-01-01

    Ideally, the original supplier of a piece of nuclear safety-related equipment has performed a qualification program and will continue to support that equipment throughout the lifetime of the nuclear power plants in which in equipment is installed. The supplier's nuclear quality assurance program will be maintained and he will continue to offer all necessary replacement parts. These parts will be identical to the original parts, certified to the original purchase order requirements, and the parts will be offered at competitive prices. Due to the changing nature of the nuclear plant equipment market, however, one or more of those ideal features are frequently unavailable when safety-related replacement equipment or parts are required. Thus, the process of equipment and parts qualification has had to adjust in order to ensure obtaining qualified replacements when needed. This paper presents some new directions taken in the qualification of replacement equipment and parts to meet changes in the marketplace