جستجوی مقالات مرتبط با کلیدواژه "itraconazole" در نشریات گروه "پزشکی"
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Background
Given the increasing resistance of Aspergillus spp. to azoles, finding effective new compounds, such as the spirocyclopropane oxindoles (4a-4b-4c) derivatives, seems necessary. The present study aimed to evaluate the antifungal activity of spirocyclopropane oxindoles (4a-4b-4c) derivatives against Aspergillus spp.
MethodsIn vitro, the cytotoxicity of the synthesized compounds was evaluated against MCF-7 cancer cell lines using the MTT assay. In the next step, the antifungal susceptibility of 50 Aspergillus isolates of clinical origin to spirocyclopropane oxindoles (4a-4b-4c) derivatives and itraconazole was evaluated according to CLSI (Clinical and Laboratory Standards Institute) M38A2 guidelines. Statistical analysis was performed using SPSS software, version 20, and the significance level was considered P<0.05.
ResultsThe results revealed that 4c exhibited the lowest toxicity to MCF-7 cells among the three synthesized compounds. However, this level of toxicity was higher than control. The present study shows a significant difference between the minimum inhibitory concentration (MIC) of 4a-4b-4c oxindole derivatives of spirocyclopropane and itraconazole against Aspergillus spp. Comparing the MIC values of 4a, 4b, and 4c oxindole spirocyclopropane derivatives with each other, 4b derivatives have lower MIC values for Aspergillus flavus and Aspergillus fumigatus isolates. In addition, 4c derivatives had the highest MIC for Aspergillus terreus.
ConclusionAlthough the antifungal effects of spirocyclopropane oxindoles (4a-4b-4c) on Aspergillus spp. were significantly lower than itraconazole, we hope to increase the antifungal effects of these compounds with structural changes.
Keywords: Spirocyclopropane Oxindoles Derivatives, Itraconazole, Aspergillus -
Background and Purpose
Considering the possible role of fungal sensitization in the treatment of resistant asthma, which may lead to the remodeling of bronchial structure, we theorized that itraconazole could result in better control of asthma. In this regard, this study aimed to compare the effects of itraconazole and prednisolone (routinely prescribed) on clinical, structural, and biomarker findings of the remodeling of asthma.
Materials and MethodsThis double-blind controlled randomized clinical trial was performed on 70 adult patients suffering from severe persistent asthma. The intervention group received 200 mg of itraconazole per day, and the control group received 10 mg of prednisolone per day, for 32 weeks, in addition to the classic treatment of asthma. The subjects were randomly divided into two groups, and assigned by sealed envelope. Blinding was performed by repacking the drug in a similar container. Primary outcomes were asthma control test score, fibroblast growth factor 2, and wall area percentage on RB1 bronchus measured by computed tomography. The outcomes were compared in subjects classified as allergic, eosinophilic, T2 low asthma, and four types of inflammatory cell classification in sputum.
ResultsSeventy subjects finished the 32-week trial (35 subjects in each group). Baseline data did not show significant differences between groups. A comparison of asthma variants showed significantly more severe cough and dyspnea in the allergic variant and higher spirometry results in T2-low asthma. Sputum cytology revealed a mixed pattern as the most frequent type (47%). After the trial, two groups improved in many parameters; however, FGF-2 improved more significantly by itraconazole (4.66±16.92 decreased to 1.14±2.98), and FEV1/FVC was significantly higher in the itraconazole group,compared to the control group. These results did not change in terms of asthma variants and sputum classification.
ConclusionItraconazole was superior to prednisolone in the treatment of many clinical and spirometry aspects in severe persistent asthma.
Keywords: Asthma, Bronchial wall thickness, Fibroblast growth factor 2, itraconazole, Prednisolone, Remodeling -
زمینه و هدف
کاندیدا آلبیکنس توانایی کلونیزه کردن سطوح زنده و غیرزیست و تشکیل بیوفیلم هایی را دارد که در برابر ضدقارچ های رایج بسیار مقاوم هستند. مطالعه حاضر به منظور ارزیابی فعالیت قارچ کشی ایتراکونازول بروی بیوفیلم کاندیدا آلبیکنس طراحی شده است.
روش اجرا:
مطالعه حاضر بر روی 10 نمونه ناخن انجام شد. آزمایش روتین قارچ شناسی و مولکولی جهت شناسایی و تعیین گونه قارچ انجام شد. بیوفیلم در پلیت 96 خانه تشکیل شد و در مجاورت ایتراکونازول قرار گرفت. تجمع گونه های اکسیژن فعال ROS اندازه گیری و سطح ROS در بیوفیلم های تیمارشده با ایتراکونازول در حضور آنتی اکسیدان تعیین شد. اندازه گیری حداقل غلظت مهاری ایتراکونازول در حضور اسید اسکوربیک (10 میلی مولار) براساس پروتکل مرحله قبل انجام شد. برای بررسی احتمال القای آپوپتوز به دنبال مصرف ایتراکونازول از کیت تشخیص آپوپتوز Annexin V-FITC استفاده شد.
یافته هاMann-Whitney تفاوت معنی داری را بین بیوفیلم های تیمارشده با ایتراکونازول و بیوفیلم های تیمارنشده برای 10 سویه آزمایش شده نشان داد. درمان با ایتراکونازول منجر به کاهش قابل توجهی در تعداد بیوفیلم شد. اسید اسکوربیک به طور قابل توجهی تجمع ROS ناشی از ایتراکونازول را برای بیوفیلم های همه سویه های کاندیدا آلبیکنس کاهش داد. یافته ها نشان می دهد که ایتراکونازول آپوپتوز وابسته به ROS را در یک حالت وابسته به دوز در سلول های بیوفیلم القا می کند.
نتیجه گیریدر این مطالعه مشخص شد وجود ROS درون سلولی عامل اصلی مکانیسم آپوپتوز ایتراکونازول است. توانایی ایتراکونازول برای القای ROS در سلول های کاندیدا یک استراتژی قارچ کشی بسیار موثر به نظر می رسد.
کلید واژگان: اونیکومایکوزیس, ایتراکونازول, آپوپتوزBackground and AimCandida albicans have the ability to colonize living and non-living surfaces and form biofilms that are very resistant to common antifungals. The present study was designed to evaluate the fungicidal activity of itraconazole on Candida albicans biofilm.
MethodsThe present study was conducted on 10 nail samples. Routine mycological and molecular tests were performed to identify and determine the type of fungus. Biofilm was formed in the 96-well plate and was subjected to the itraconazole. ROS accumulation was measured. ROS levels were determined in biofilms treated with itraconazole in the presence of antioxidants.The minimum inhibitory concentration of itraconazole was measured in the presence of ascorbic acid (10 mM) according to the protocol of the previous step. Annexin V-FITC apoptosis detection kit was used to investigate the possibility of apoptosis induction following itraconazole use.
ResultsMann-Whitney showed a significant difference between biofilms treated with itraconazole and untreated biofilms for 10 tested strains. Treatment with itraconazole resulted in a significant reduction in the number of biofilms. Ascorbic acid significantly reduced ROS accumulation caused by itraconazole for biofilms of all Candida albicans strains. The findings show that itraconazole induces ROS-dependent apoptosis in a dose-dependent manner in biofilm cells.
ConclusionIn this study, it was found that the presence of intracellular ROS is the main cause of the apoptosis mechanism of itraconazole. The ability of itraconazole to induce ROS in Candida cells appears to be a very effective fungicidal strategy.
Keywords: onychomycosis, itraconazole, apoptosis -
Background and Purpose
Fungal infection by species of pathogenic Candida withantifungal resistance is currently a serious problem. Treatment with new medications isbecoming more challenging to manage this type of infection. The present study aimed to investigate the antifungal effect of essential oils (EOs) against itraconazole-resistantspecies of pathogenic Candida.
Materials and MethodsSeven essential oils were tested on 15 clinical isolates ofitraconazole-resistant Candida from patients with vulvovaginal candidiasis. Theantifungal action of selected EOs was evaluated using the disc diffusion method with the determination of the minimum inhibitory concentration (MIC) of effective EOs.
ResultsRadish EO was the most effective type against all Candida isolates with MICsbetween 3.125% and 6.25% (v/v) .It also had a stronger effect than itraconazole. Sixother EOs showed antifungal effects at varying concentrations and were dependent upon the type of isolate. Low concentrations of these six EOs were more effective against many isolates than their high concentrations. Moreover, camphor and linseed EOs were less effective on isolates.
ConclusionRadish EO has a strong antifungal activity against itraconazole-resistancespecies of Candida, even more than itraconazole. The antifungal action of some EOs can be increased through the use of low concentrations.
Keywords: Candida, Essential oil, itraconazole, Radish, Resistance -
The purpose of this study was to evaluate the effect of 8 months of treatment with itraconazole on airway wall thickness in patients with severe persistent asthma. It was a double-blind, randomized, placebo-controlled clinical trial (IRCT20091111002695N9). Seventy-five subjects with severe persistent asthma received itraconazole (100 mg), prednisolone (5 mg), or placebo twice a day for eight months in three treatment groups (n=25 in each group). The primary objective was to improve the right upper lobe apical segmental bronchus (RB1) wall thickness percentage measured by high-resolution computed tomography scan of the lungs. Other morphometric measurements of RB1, asthma control test (ACT) score, presence of wheezing, dyspnea severity, rate of asthma exacerbation, fractional exhaled nitric oxide (FeNO), and expiratory volume in 1 second (FEV1) were set as the secondary outcomes. Wall thickness percentage reduced significantly from 46% to 43.7% from pre- to post-treatment in the itraconazole-treated subjects. Similarly, lumen area and radius increased significantly in both the prednisolone and itraconazole groups. Itraconazole led to a significant improvement in wheezing, dyspnea severity, FEV1, ACT score, and FeNO. Although prednisolone was also effective in improving pulmonary function tests and ACT scores, it was associated with significantly more side effects than itraconazole. Long-term treatment with itraconazole resulted in a significant reduction in bronchial wall thickness and improvements in clinical findings and pulmonary function tests. Thus, itraconazole could be a helpful add-on treatment option for severe persistent asthma patients to achieve better disease control.
Keywords: Airway remodeling, Asthma, Itraconazole, X-ray computed tomography -
سابقه و هدف
با توجه به گسترش مقاومت های دارویی به آزول در میان گونه های کاندیدا یافتن ترکیبات جدید موثر در شرایط آزمایشگاه مانند مشتقات 3،4-دی-هیدروپیریمیدین حایز اهمیت می باشد. هدف از مطالعه حاضر، ارزیابی حساسیت ضدقارچی مشتقات 3،4-دی-هیدروپیریمیدین-1-(H2)-ال-H1- پیرول بر روی ایزوله های بالینی کاندیدا می باشد.
مواد و روش ها:
حساسیت دارویی 102 ایزوله کاندیدا با منشا اتومایکوزیس نسبت به مشتقات دی- هیدروپیریمیدین و داروی ایتراکونازول به روش میکرودایلوشن براث و بر اساس دستورالعمل CLSI-M27S4 ارزیابی شد. دامنه رقت دارویی ترکیبات و داروی ضدقارچ 16-0/016 میکروگرم/ میلی لیتر بود. غلظتی از ترکیبات که حداقل 50 درصد مهار رشد نسبت به گروه کنترل مثبت مشاهد شد به عنوان MIC (حداقل غلظت مهاری رشد) در نظر گرفته شد. آنالیز آماری با نرم افزار20 SPSS انجام شد.
یافته ها:
نتایج نشان داد مشتقات 3،4-دی- هیدروپیریمیدین-1-(H1)-ال-H2- پیرول، دارای MIC بیش تری نسبت به داروی ایتراکونازول علیه گونه های کاندیدا هستند. هم چنین در مقایسه مقادیر MIC های مشتقات 3، 4-دی-هیدروپیریمیدین با یکدیگر (P1-P4)، مشتقات P1 مقادیر MIC پایین تری نسبت به سه مشتق دیگر داشت و تقریبا تمامی ترکیبات علیه کاندیدا آلبیکنس کارایی بیش تری را نسبت به گونه های دیگر کاندیدا از خود نشان دادند .
استنتاجبا وجود این که اثرات ضد قارچی مشتقات 3، 4-دی-هیدروپیریمیدین-1-(H2)-ال-H1- پیرول علیه گونه های کاندیدا در مقایسه با داروی ضدقارچی ایتراکونازل به طور معناداری کم تر بود ولی می توان با ایجاد تغییرات ساختاری در این ترکیبات، اثرات ضدقارچی آن ها را افزایش داد.
کلید واژگان: مشتقات 3, 4-دی-هیدروپیریمیدین-1-(H2)-ال-H1- پیرول, ایتراکونازول, گونه های کاندیداBackground and purposeThere is an increasing rate of drug resistance to azole among Candida species, so, finding new compounds that are effective in laboratory conditions, such as 3,4-dihydropyrimidine derivatives are important. The purpose of this study was to evaluate the antifungal sensitivity of 3,4-di-hydropyrimidine-1- (H2) -L- H1-pyrrole derivatives in Candida isolates.
Materials and methodsAntifungal sensitivity of 102 Candida isolates with the origin of otomycosis to dihydropyrimidine derivatives and itraconazole were evaluated by broth microdilution according to CLSI-M27S4 guidelines. The serial dilution range of compounds and antifungal drug was 0.016-16 μg/ml. A concentration of compounds that showed at least 50% growth inhibition compared to the positive control group was considered as the minimum inhibitory concentration (MIC). Statistical analysis was performed in SPSS V16.
ResultsFindings showed that 3,4-di-hydropyrimidine-1-(H2)-L-H1-pyrrole derivatives have higher MIC than itraconazole against Candida species. Also, comparing the MIC values of 3,4-di- hydropyrimidine with each other (P1-P4), P1 derivatives were found with lower MIC values than the other three derivatives and almost all compounds showed more efficacy against Candida albicans than other Candida species.
ConclusionAlthough the antifungal effects of 3,4-dihydropyrimidine-1-(H2)-L-H1-pyrrole derivatives against Candida species were lower than itraconazole, but, making structural changes in these compounds can increase their antifungal effects.
Keywords: 3, 4-di-hydropyrimidine-1-(H2)-L-H1-pyrrole derivatives, itraconazole, Candida species -
Background and Objectives
Candida albicans complex species are well known as the main cause of candidiasis, particularly among susceptible individuals. In this study, we report the genetic diversity of Candida spp. and the antifungal susceptibility pattern of the cryptic C. albicans complex isolates in Kerman, Iran.
Materials and MethodsA total of 112 yeast isolates were obtained from different clinical samples, and molecular identification was performed. All C. albicans complex isolates were tested for susceptibility of them to amphotericin B, fluconazole, and itraconazole.
ResultsThe majority of clinical isolates were C. albicans complex (n=48) followed by C. glabrata complex (n=34), C. parapsilosis complex (n=21), and C. krusei (n=9). Among C. albicans complex, 45 isolates were C. albicans (94%), 2 isolates were C. dubliniensis (4%), and 1 isolate was C. africana (2%). Amphotericin B was the most active antifungal, whereas 8.9% and 6.7% of the isolates were resistant to fluconazole and itraconazole, respectively.
ConclusionRegarding the high incidence of Candida infections particularly in susceptible populations and the emergence of an infrequent yeast species with elevated MICs, which is indistinguishable with conventional methods, developing accurate molecular methods for laboratory diagnosis should be considered in the clinical setting.
Keywords: Candida albicans, Candidiasis, Polymerase chain reaction, Amphotericin B, Itraconazole -
Purpose
The objective of this study was to design and develop nanoemulsion formulations of Itraconazole (ITZ), a water-insoluble, potent antifungal drug using the spontaneous emulsification method, to improve the ocular delivery and achieve a sustained release of the drug.
MethodsThe oil was selected on the basis of the ITZ solubility while the surfactant and co-surfactant were selected based on the thermodynamic stability and globule size. Following the selection of components, a pseudo-ternary phase diagram was constructed for the most promising formulation (F11) using benzyl benzoate (BB) as the oil, Eumulgin CO40 as the surfactant, and propylene glycol as the co-surfactant, by the design of experiments (DoE).
ResultsF7 and F11 formulations were found to have an average globule size of 223.5 ± 10.7 nm and 157.5 ± 14.2 nm, besides thermodynamic stability and suitable physicochemical properties. F11 possessed an almost seven-fold higher cumulative percentage of in vitro released ITZ, in comparison to ITZ aqueous suspension after 24 hours. The release data suggested that the best fitted kinetical model for F11 and F7 was the Higuchi and Korsmeyer-Peppas model.
ConclusionThe extended-release of the drug beside an acceptable amount of loaded ITZ suggested that nanoemulsion is suitable for the delivery of the ITZ.
Keywords: Antifungal drugs, Bioassay, Itraconazole, Nanoemulsion, Ocular drug delivery -
International Journal of Molecular and Clinical Microbiology, Volume:10 Issue: 2, Summer and Autumn 2020, PP 1360 -1368Aspergillus fumigatus is an opportunistic fungal pathogen causes invasive aspergillosis in immunocompromised patients. Raphanus sativus L. var. niger and Trachyspermum ammi are two medical herbs which seemed to have an antifungal activity that can be integrated alternative medicine into conventional medicine. The aim of study was to evaluate the effect of R. sativus and T. ammi on the resistant and susceptible A. fumigatus isolates.In present study, 185 environmental samples from 11 cities of Iran were processed and screened in terms of azole resistance using selective plates. The isolates were confirmed by partial sequencing of the b-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents and R. niger and T. ammi extract were performed based on the CLSI, M38-A2 document. The ingredients in the extract by gas chromatography method were isolated and identified by mass spectrometry. Overall, 51 A. fumigatus isolates were detected. According to in vitro antifungal susceptibility tests, 45 A. fumigatus isolates had high MICs of itraconazole (≥8 mg/L) and voriconazole (>2 mg/L) and 6 A. fumigatus isolates were susceptible. The MIC 50 and MIC 90 for R. sativus was 1.95 mg/ml and 3.9 mg/ml respectively. Also, The MIC 50 and MIC 90 for trachyspermum ammi was recorded as 2.30 mg/ml and 4.85 mg/ml respectively. The main identified compounds were Tramadol (58.37%), Butanol (23.42%), Benzofuran (18.21%). Our results indicated that R. sativus and T. ammi extracts significantly inhibited the growth of A. fumigatus isolates and have an appropriate antifungal activity.Keywords: Raphanus niger, Trachyspermum ammi, Aspergillus fumigatus, Itraconazole, Voriconazole, Antifungal susceptibility, Resistant
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مقدمه
امروزه، شیوع Onychomycosis ناشی از قارچ های رشته ای غیر درماتوفیتی در حال افزایش است. از آن جایی که Aspergillus شایع ترین عامل ایجاد کننده ی این بیماری می باشد، مطالعه ی حاضر به منظور ارزیابی حساسیت دارویی سویه های بالینی Aspergillus عامل Onychomycosis نسبت به داروهای ایتراکونازول، وریکونازول و آمفوتریسین B انجام شد.
روش هااین مطالعه ی مقطعی بر روی 50 سویه ی Aspergillus جدا شده از بیماران مبتلا به Onychomycosis مراجعه کننده به آزمایشگاه های تشخیصی بیمارستان های دانشگاهی مشهد انجام شد. بر اساس بررسی فنوتیپی و مولکولی کلنی های Aspergillus، بیشترین فراوانی با 34 مورد مربوط به Aspergillus flavus بود. آزمایش حساسیت دارویی طبق شیوه نامه ی Clinical and Laboratory Standards Institute-M38-A2 (CLSI-M38-A2) انجام گرفت و میزان Minimum inhibitory concentration (MIC) داروها تعیین گردید.
یافته هااز 50 نمونه ی ناخن، 13 مورد مربوط به مردها و 37 مورد مربوط به زن ها بود. از این تعداد، 15 مورد مربوط به ناخن های دست و 33 مورد مربوط به ناخن های پا و 2 مورد به طور مشترک مربوط به ناخن های دست و پا بود. 7/14 درصد ایزوله های Aspergillus flavus با داشتن MIC > 2 میکروگرم/میلی لیتر نسبت به آمفوتریسین B به عنوان ایزوله های بالینی مقاوم تلقی شدند و حساسیت نسبت به ایتراکونازول و وریکونازول 100 درصد بود. 90 MIC داروهای آمفوتریسین B، ایتراکونازول و وریکونازول به روش Broth microdilution برای گونه ی Aspergillus flavus به ترتیب 4، 25/0 و 1 میکروگرم/میلی لیتر به دست آمد. اختلاف معنی داری در MIC دو داروی ایتراکونازول و آمفوتریسین B دیده شد (050/0 > P).
نتیجه گیریتمامی گونه های Aspergillus نسبت به داروهای ایتراکونازول و وریکونازول حساس می باشند و این دو دارو، موثرتر از آمفوتریسین B بر روی گونه های Aspergillus می باشند. با توجه به حساسیت متفاوت این گونه ها نسبت به عوامل ضد قارچی، انجام آزمایش حساسیت دارویی به منظور انتخاب داروی مناسب ضروری به نظر می رسد.
کلید واژگان: Onychomycosis, Aspergillus, ایتراکونازول, آمفوتریسینB, وریکونازولBackgroundNowadays, the prevalence of onychomycosis caused by non-dermatophyte molds is increasing. As Aspergillus is the most common etiologic agents of the disease, this study was performed to evaluate the susceptibility of clinical isolates of Aspergillus as the cause of onychomycosis to itraconazole, voriconazole, and amphotericin B.
MethodsThis cross-sectional study was performed on 50 Aspergillus strains isolated from the patients with onychomycosis referred to diagnostic laboratories of university hospitals in Mashhad, Iran. According to the phenotypic and molecular analysis of Aspergillus isolates, the most frequent species was Aspergillus flavus (A. flavus) with 34 cases. The drug susceptibility test was performed according to Clinical and Laboratory Standards Institute-M38-A2 (CLSI-M38-A2) protocol, and the minimum inhibitory concentration (MIC) of the drugs was determined.
FindingsFrom 50 patients with dystrophic nails, 13 were men and 37 were women. 15 patients had fungal infection of fingernails, and 33 patients had fungal infection on toenails; 2 patients had both infections of finger and toe nails. 14.7% of A. flavus isolates with MIC > 2 μg/ml to amphotericin B were considered as resistant clinical isolates. The sensitivity to itraconazole and voriconazole was 100%. MIC90 of amphotericin B, itraconazole, and voriconazole were obtained by broth microdilution method for A. flavus species as 4, 0.25, and 1 μg/ml, respectively. Significant difference was observed in MIC between itraconazole and amphotericin B (P < 0.050).
ConclusionAll Aspergillus species are susceptible to itraconazole and voriconazole, and these two drugs are more effective than amphotericin B on Aspergillus species. Due to the different susceptibility of these species to antifungal agents, it is necessary to perform drug susceptibility testing in order to select the appropriate drug.
Keywords: Onychomycosis, Aspergillus, Itraconazole, Amphotericin B, Voriconazole -
Background and Purpose
Itraconazole therapy has been reported to control asthma in severe therapy-resistant asthma with fungal sensitization. The aim of this study was to investigate the impact of anti-fungal therapy on the treatment of severe asthma, irrespective of sensitization.
Materials and MethodsThis active comparator clinical trial was performed on 110 therapy-resistant asthmatic patients who were randomly assigned into two groups of case and control. The patients in the case group were administered 200 mg itraconazole twice a day and the control group received 10 mg prednisolone after breakfast for 4 months. The asthma control test (ACT) which was used as a marker for the global evaluation of treatment effectiveness (GETE) was applied as the primary endpoint parameter. Cough, dyspnea, and sleep disturbance were measured on a scale of 1-4, with 1 representing no symptom and 4 indicating severe exhausting disturbance.
ResultsBased on the obtained results, 71% of the itraconazole group demonstrated a marked improvement in the GETE score after a four-month treatment. Itraconazole was able to suppress clinical symptoms, including cough, dyspnea, and night symptoms, and their physical exam was indicative of normalization in 60% of the patients. On the other hand, the patients in the parallel group "prednisolone" were only able to control dyspnea. The ACT score represented a notable improvement with itraconazole (mean: 14 before the trial and >20 after the trial) and spirometry parameters underwent a considerable change from obstructive pattern to normal. Furthermore, adverse effects were only detected in 6% of itraconazole users.
ConclusionThe results of this clinical trial indicted the effectiveness of antifungal therapy for the control of the clinical condition of a subgroup of patients with severe steroid-refractory asthma.
Keywords: Anti-fungal therapy, Asthma, Fungal sensitization, itraconazole, Resistant asthma, Triazole -
Patients with impaired immunity are at particular risk of infections with Candida albicans. Antifungal drugs such as azoles commonly used for candidiasis treatment, but drug resistance is one of the most common problems for public health. The aim of this study was to evaluate the expression of lanosterol 14-demethylase (ERG11) gene for three-drug combinations in C. albicans. Disk diffusion and broth microdilution susceptibility tests were employed to evaluate the synergic effects of amphotericin B, fluconazole, voriconazole, ketoconazole and itraconazole. Quantification of ERG11 gene expression was carried out in C. albicans treated with three-drug combinations of fluconazole/ ketoconazole/ voriconazole and fluconazole/ ketoconazole/ itraconazole. Three-drug combinations revealed synergistic and partial synergistic effect for all tested isolates (FIC index range of 0.27-0.77). The expression levels of ERG11 were down-regulated by three-drug combination of fluconazole/ ketoconazole/ voriconazole treatment. Fluconazole synergizes with ketoconazole and voriconazole in three-drug combination against C. albicans by targeting of the ERG11 gene.Keywords: Candida albicans, Fluconazole, ERG11, Itraconazole, Ketoconazole, Synergic effect, voriconazole
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اهدافدر این مطالعه، جایگزنی ترکیبات طبیعی مانند چای سبز بجای استفاده از داروهای شیمیایی ایتراکونازول و وریکونازول بررسی شد.مواد و روش هادر این پژوهش میزان اثرات ضد قارچی عصاره های آبی و متانولی چای سبز و همچنین اثرات هم افزایی این دو عصاره با دو داروی ایتراکونازول و وریکونازول بر روی چهار سویه آسپرژیلوس مطابق روش رقت در پلیت الایزا با تعیین حداقل غلظت مهاری و حداقل غلظت قارچ کشی موردبررسی قرار گرفت.یافته هادوسویه آسپرژیلوس فلاووس 39 ATCC و آسپرژیلوس ترئوس 274 ATCC نسبت به داروی ایتراکونازول حساس و دوسویه دیگر مقاوم بودند. تمامی 4 سویه موردبررسی نسبت به وریکونازول مقاوم بودند. دو عصاره آبی و متانولی چای سبز، اثر ضد قارچی از خود نشان ندادند اما اثرات هم افزایی در ترکیب عصاره آبی چای سبز و ایتراکونازول در دو سویه آسپرژیلوس فومیگاتوس ATCC278 و آسپرژیلوس نایجرATCC9142 ارزشمند بود و همچنین دو ترکیب عصاره متانولی چای سبز و ایتراکونازول در آسپرژیلوس نایجر ATCC9142 و دو ترکیب عصاره آبی چای سبز و وریکونازول بر روی آسپرژیلوس فلاووس 39 ATCC و آسپرژیلوس فومیگاتوس ATCC278 ارزشمند گزارش شد.نتیجه گیرینتایج حاصل از این پژوهش بیانگر وجود اثرات هم افزایی ارزشمندی بین ترکیبات داروها و عصاره های مورد آزمایش بود.کلید واژگان: چای سبز, ایتراکونازول, وریکونازول, آسپرژیلوسAims: In this study, the replacement of natural compounds such as green tea by chemical drugs like itraconazole and voriconazole was studied.Materials and MethodsIn this study, the effects of the aqueous and methanol extracts of green tea and the synergistic effects of these two extracts were studied along with two drugs of itraconazole and voriconazole against four strains of Aspergillus accordaing to microdilution method to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC).
Findings: Two strains of A.flavus ATCC39 and A.terreus ATCC274 are sensitive to itraconazole while two other strains were resistant. All four tested strains were resistant to voriconazole. The aqueous and methanol extracts of green tea did not show antifungal effect but synergistic effects of aqueous extract of green tea and itraconazole were worthwhile against A.niger ATCC9142 and A.fumigatus ATCC278. Also, the combined methanol extracts of green tea and itraconazole against A.niger ATCC9142 and the combined aqueous extracts of green tea and voriconazole against A.flavus ATCC 39 and A.fumigatus ATCC278 were reported valuable.ConclusionThe results of this study showed that there is a valuable synergistic effect between the tested antifungal drugs and the extracts.Keywords: Green Tea, Itraconazole, Voriconazole, Aspergillus -
Background And ObjectivesColonization of Candida species is common in pediatric patients admitted to hematology-oncology wards. The aim of this study was to identify colonized Candida species and their susceptibility patterns in hematologic pediatric patients.Materials And MethodsSamples were collected from mouth, nose, urine and stool of the patients admitted to five university hospitals and cultured on sabouraud dextrose agar. The isolates were identified by API 20 C AUX system and their susceptibility patterns were evaluated by CLSI M27-A3 and S4.ResultsFrom 650 patients, 320 (49.2%) were colonized with 387 Candida species. Candida albicans was the most prevalent isolated species, followed by Candida glabrata, Candida tropicalis, Candida famata, Candida kefyr and Candida kuresi. The epidemiological cut off value (ECV) for all Candida species to amphotericin B was ≤0.25 μg except C. krusei (4 μg). The resistance rate to fluconazole in this study in C. albicans was 4.9% with ECV 8 μg/ml, followed by C. tropicalis 8.8% with ECV 0.5 μg/ml. Voriconazole and posaconazole were effective antifungal agents for all Candida isolates. The ECV of C. albicans, Candida parapsilosis, C. tropicalis, C. glabrata and C. krusei for itraconazole were 0.5, 0.25, 0.5, 1 and 2 μg, respectively. The resistant and intermediate rates of Candida species to caspofungin in this study were 2.9%, 5.9%, 18.8%, 47.9%, 0.0% and 16.7% in C. tropicalis, C. glabrata and C. parapsilosis respectively.ConclusionC. albicans was the most prevalent species in pediatric colonized patients. New azole agents like voriconazole and posaconazole are effective against non- albicans Candida species. Increase in intermediate species is alarming to future emerging resistant species.Keywords: Candida species, Colonized, Amphotericin B, Voriconazole, Posaconazole, Itraconazole
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BackgroundInvasive fungal infections without proper treatment could lead to high mortality rate, especially in immunocompromised patients. Candida species distribution and drug susceptibility patterns vary in different areas. Understanding the etiologic agents and drug susceptibility patterns in each region are required for the best management of patients with Candida infections.ObjectivesThe aim of this study was to identify Candida species isolated from clinical samples of six university hospitals in Iran and detect their susceptibility patterns to seven antifungal agents.MethodsClinical samples from patients with fungal infections were cultured on Sabouraud dextrose agar. Isolated yeasts were identified by API 20C AUX kit, according to the manufacturers instructions. Drug susceptibility patterns to amphotericin B, caspofungin, voriconazole, fluconazole, posaconazole, itraconazole and ketoconazole were determined, according to CLSI M27-A3 and S4.ResultsIn total, 428 species of Candida were isolated from clinical samples (1950 samples). Most isolated species were Candida albicans, followed by C. tropicalis, C. parapsilosis, C. kefyr, C. famata, C. glabrata, C. krusei, C. dubliniensis, C. guilliermondii and C. lusitaniae. Sensitivity rate of C. albicans to amphotericin B, caspofungin, voriconazole, fluconazole, and itraconazole was 96.6%, 99.5%, 88.6%, 90.6%, and 52% with MIC90 values equal to 0.25 µg/mL, 0.125 µg/mL, 0.125 µg/mL, 2 µg/mL, and 1 µg/mL, respectively. The MIC 90 values for ketoconazole and posaconazole were 0.125 µg/mL and 0.064 µg/mL, respectively. Different sensitivity to antifungal agents was present in non-albicans Candida species especially in C. krusei, C. glabrata, and C. tropicalis.ConclusionsAccording to this study, C. albicans is the most prevalent etiologic agent in infected patients and caspofungin is the most effective antifungal agent. Knowledge about etiologic agents and their susceptibility patterns in each region is helpful for successful treatment of the patients.Keywords: Candida albicans, Fluconazole, Amphotericin B, Itraconazole, Candida tropicalis
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Background andPurposeAspergillosis is one of the most common opportunistic fungal infections in immunocompromised and neutropenic patients. Aspergillus fumigatus (A. fumigatus) is the most common causative agent of this infection. Due to variable CO2 concentrations that pathogens are exposed to during the infection process and to understand the role of CO2, we examined the effects of various CO2 concentrations as one of the environmental factors on morphological changes and induction of antifungal resistance in A. fumigatus.Materials And MethodsA. fumigatus strains were cultured and incubated under 1%, 3%, 5%, and 12% CO2 atmospheres, each time for one, two, and four weeks. The control culture was maintained for one week without CO2 atmosphere. Morphological changes were investigated and antifungal susceptibility test was performed according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The results of different CO2 atmospheres were compared with that of the control sample.ResultsWe found that 1%, 3%, 5%, and 12% CO2 atmospheres were associated with morphological colony changes. Macroscopically, the colonies were shallow dark green, smooth, crisp to powdery with reduced growth; microscopic examination revealed the absence of conidiation. The induction of antifungal resistance in the susceptible strains to itraconazole, voriconazole, and amphotericin B increased after exposure to 12% CO2 atmosphere and four weeks of incubation. The MIC values for itraconazole, voriconazole, and amphotericin B were 16 g/ml, 1 g/ml, and 16 g/ml, respectively. These values for the control group were 0.125 g/ml, 0.125 g/ml, and 2 g/ml, respectively.ConclusionExposure to different CO2 atmospheres induced morphological changes in A. fumigatus, it seems to increase the MIC values, as well. In parallel, resistance to both itraconazole and voriconazole was also observed.Keywords: Aspergillus fumigatus, Carbon dioxide, Itraconazole, Voriconazole
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Background
Diabetic patients are more susceptible to cutaneous fungal infections. The higher blood sugar levels cause increasing the cutaneous fungal infections in these patients. The main objective of this study was to find the frequency of fungal infections among cutaneous lesions of diabetic patients and to investigate azole antifungal agent susceptibility of the isolates.
Materials and MethodsIn this study, type 1diabetes (n = 78) and type 2 diabetes (n = 44) comprised 47 cases (38.5%) with diabetic foot ulcers and 75 cases (61.5%) with skin and nail lesions were studied. Fungal infection was confirmed by direct examination and culture methods. Antifungal susceptibility testing by broth microdilution method was performed according to the CLSI M27‑A and M38‑A references.
ResultsOut of 122 diabetic patients, thirty (24.5%) were affected with fungal infections. Frequency of fungal infection was 19.1% in patients with diabetic foot ulcer and 28% of patients with skin and nail lesions. Candida albicans and Aspergillus flavus were the most common species isolated from thirty patients with fungal infection, respectively. Susceptibility testing carried out on 18 representative isolates (13 C. albicans, five C. glabrata) revealed that 12 isolates (10 C. albicans and two C. glabrata isolates) (66.6%) were resistant (minimum inhibitory concentration [MIC] ≥64 mg/ml) to fluconazole (FCZ). Likewise, eight isolates (80%) of Aspergillus spp. were resistant (MIC ≥4 mg/ml), to itraconazole.
ConclusionOur finding expands current knowledge about the frequency of fungal infections in diabetic patients. We noted the high prevalence of FCZ‑resistant Candida spp., particularly in diabetic foot ulcers. More attention is important in diabetic centers about this neglected issue.
Keywords: Diabetes, diabetic foot ulcer, fluconazole, itraconazole -
سابقه و هدفکاندیدیازیس یک بیماری شایع است که توسط سویه های مختلف کاندیدا ایجاد می گردد. گیاهان دارویی هم چون جینسینگ از دیرباز به منظور درمان انواع بیماری به کار رفته اند. این مطالعه به منظور مقایسه اثر ضد قارچی عصاره الکلی گیاه جینسینگ با ایتراکونازول روی سویه های کاندیدا آلبیکنس و کاندیدا کروزه ای انجام شد.مواد و روش هابرای انجام این مطالعه مقطعی تعداد 22 سویه کاندیدا آلبیکنس و 8 سویه کاندیدا کروزه ای استفاده شد که از واژن، ادرار و خلط بیماران جدا شده بود. تست حساسیت دارویی به روش میکرودایلوشن (CLSI M27-A) و انتشار روی دیسک توسط داروی ایتراکونازول (gμ10) و عصاره جینسینگ با رقت های 1، 2، 4، 8، 16، 32، 64 و 128 میلی گرم بر میلی لیتر انجام شد. سویه های استاندارد کاندیدا آلبیکنسPTCC5027 و کاندیدا کروزه ای PTCC5295 به منظور ارزیابی کنترل کیفی استفاده شدند.نتایجکمترین و بیشترین میزانMIC (Minimum Inhibitory Concentration) در کاندیدا آلبیکنس و کاندیدا کروزه ای به ترتیب 0/0625 و 0/5 میکروگرم بر میلی لیتر برای ایتراکونازول به روش میکرودایلوشن بود، درحالی که کمترین میزان MIC و MFC (Minimum Fungicidal Concentration) در مورد عصاره الکلی 64 میلی گرم بر میلی لیتر بود. بیشترین قطر هاله برای سویه کاندیدا آلبیکنس در مورد عصاره الکلی، 14 میلی متر و محدوده قطر هاله در مورد ایتراکونازول 32-14 میلی متر بود. اختلاف معنی داری میان عصاره الکلی با رقت های 64 و 128 میلی گرم بر میلی لیتر با دارو در دو روش مذکور مشاهده نشد. (P<0.05)نتیجه گیریبا توجه به میزانMIC و هاله عدم رشد اطراف دیسک، عصاره الکلی جینسینگ با رقت های 64 و 128 میلی گرم بر میلی لیتر دارای اثر ضد قارچی قابل مقایسه با ایتراکونازول می باشد.کلید واژگان: عصاره جینسینگ, کاندیدا آلبیکنس, کاندیدا کروزه ای, ایتراکونازولFeyz, Volume:21 Issue: 3, 2017, PP 211 -217BackgroundCandidiasis is a prevalent disease which is caused by different species of Candida. Herbal drugs (e.g. ginseng) were traditionally administrated for the treatment of different diseases. This study was carried out to compare the effect of alcoholic extract of ginseng with Itraconazole against Candida albicans (C. albicans) and Candida krusei (C. krusei).
Material andMethodsThis cross-sectional study was crried out on 22 and 8 species of C.albicans and 8 C.krusei, respectively which were isolated from vagina, urine and sputum of the patients. Using the CLSI M27 and disk diffusion methods the susceptibility test was done by Itraconazole (10 µg) and ginseng extract (1, 2, 4, 8, 16, 32, 64 and 128 mg.ml-1). The standard species of C. albicans (PTCC 5027) and C. Krusei (PTCC 5295) were used for the quality control purposes.ResultsThe lowest and highest minimum inhibitory concentration (MIC) for C. albicans and C. Kruzei was 0.0625 and 0.5 μg.ml-1, respectively for Itraconazole using the microdilution method. However, the lowest MIC and minimum fungal concentration (MFC) for alcoholic extract was 64 mg.ml-1 .The highest inhibition zone for C. albicans was 14 and 14-32 mm for alcoholic extract and Foritraconazole, respectively. Using the two methods no significant difference was seen between the alcoholic extract of ginseng (64 and 128 mg.ml-1) and the drug. (PConclusionConsidering the MICs and disk diffusion results, the ginseng extract (64,128 mg.ml-1) shows considerable antifungal effects compared to Itraconazole.Keywords: Ginseng extract, Candida albicans, Candida Krusei, Itraconazole -
Background andPurposeNaganishia albida (formerly Cryptococcus albidus) is a non-neoformans cryptococcal species rarely isolated as a human pathogen.
Case report: Herein, we present the case of a 26-year-old Iranian man with a superficial cutaneous lesion in the axilla. The initial treatment for pityriasis versicolor by clotrimazole was unsuccessful. We performed skin sampling based on the standard protocol and conducted further investigations by the conventional laboratory tests and molecular analysis of the skin samples. All the mentioned analyses revealed N. albida as the causative agent of infection. The minimum inhibitory concentration (MIC) analysis was carried out for the isolated agent, and the patient was treated using 100 mg daily of oral itraconazole.ConclusionN. albida can be the causative agent of some superficial infections. This is the first report on the successful detection and treatment of a superficial skin infection due to N. albida by oral itraconazole.Keywords: Cutaneous, Cryptococcus albidus, Infection, Itraconazole, Naganishia albida, Superficial -
IntroductionThe increase in candidaemia is associated with high mortality and morbidity in the developed countries. A trend has been observed in the relative frequency of each Candida spp. isolated from blood. Polyenes, allylamines, azoles are the only available antifungal treatment option for systemic and invasive candidiasis. In past few decades the incidence of resistance in antifungal treatment of candida species is increasing rapidly, which may be a issue of concern with the health care professional. Studies on prevalence of infections and antifungal susceptibility testing are useful in deciding clinical strategies.
Aims: To do species level identification and detect antifungal susceptibility of candida species isolated from blood culture.MethodologyFrom total 70 patients from a tertiary care hospital of Kolkata, Candida species were isolated from blood culture and antifungal susceptibility was done by the Vitek 2- compact automated system.ResultsOut of total 70 samples, C. albicans were isolated from 34 (48.57%), among other non albicans, C. non albicans species 12 (17.14%), followed by Candida tropicalis 10 (14.29%). Out of 34 C. albicans antifungal susceptibility was done for 28 isolates in which all isolates were sensitive to Fluconazole, and resistance Amphotericine B, Flucytosine, Voriconazole and Itraconazole in 44.12%, 52.94%, 8.82% and 17.65% cases respectively. For other candida species (other than C. albicans) , antifungal susceptibility was done for 27 isolates among which resistance of Amphotericine B, Fluconazole, Flucytosine, Voriconazole, Itraconazole was found in 29.63%, 44.44%, 14.82%, 14.82% and 22.22% cases respectivelyKeywords: Candida albicans, Fluconazole, Voriconazol, Itraconazole
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