Combinations Of Antifungal Drugs Research Articles

Theoretical aspects of the creation and pharmaceutical analysis of ointment combinations of antifungal and anti-inflammatory drugs with Tizol gel

Theoretical aspects of the creation and pharmaceutical analysis of ointment combinations of antifungal and anti-inflammatory drugs with Tizol gel

Effectiveness and safety of combination of Itraconazole and Amorolfine in management of patients with recalcitrant multi-site dermatophytosis who failed previous combination antifungal therapy

There is alarming rise in cases of dermatophytosis in India.Standard treatment recommendations are no longer working. Combination of topical and systemic antifungal drugs is one of the most frequently used treatment strategy.This was an open label, prospective, interventional, non-comparative study. Effectiveness endpoints were percentage of patients achieving complete cure, clinical cure and mycological cure at the end of the treatment period from baseline. Safety was assessed by analyzing the AEs and monitoring of liver function tests. 66 patients were included in the study. 75.75%, 86.36% and 81.8% patients achieved complete cure, clinical cure and mycological cure respectively at the end of the study period. There was improvement in each symptom during study duration as observed during each follow up visit on week 2, 4 and 6. Total of 10.60% reported 1 or more drug related AE. Nausea was most common side effect followed by vomiting, headache and edema of face. All the AEs were mild in nature and resolved during study. To conclude the result of this study shows that the combination therapy of oral itraconazole and topical amorolfine represents an improved treatment strategy for patients with recalcitrant multisite tinea infections.

Formulation of Tioconazole and Melaleuca alternifolia Essential Oil Pickering Emulsions for Onychomycosis Topical Treatment.

Onychomycosis is a disease that affects many adults, whose treatment includes both oral and topical therapies with low cure rates. The topical therapy is less effective but causes fewer side effects. This is why the development of an effective, easy to apply formulation for topical treatment is of high importance. We have used a nanotechnological approach to formulate Pickering emulsions (PEs) with well-defined properties to achieve site-specific delivery for antifungal drug combination of tioconazole and Melaleuca alternifolia essential oil. Silica nanoparticles with tailored size and partially hydrophobic surface have been synthesized and used for the stabilization of PEs. In vitro diffusion studies have been performed to evaluate the drug delivery properties of PEs. Ethanolic solution (ES) and conventional emulsions (CE) have been used as reference drug formulations. The examination of the antifungal effect of PEs has been performed on Candida albicans and Trichophyton rubrum as main pathogens. In vitro microbiological experimental results suggest that PEs are better candidates for onychomycosis topical treatment than CE or ES of the examined drugs. The used drugs have shown a significant synergistic effect, and the combination with an effective drug delivery system can result in a promising drug form for the topical treatment of onychomycosis.

Effect of Salicylic Acid 3% + Benzoic Acid 6% (Whitfield’s Ointment), Clotrimazole 1% Cream, and Systemic Terbinafine on Mild-to-Moderate Tinea Corporis: A Randomized Comparative Study

Abstract Introduction The various epidemiological studies conducted on dermatophytic infection in different parts of India have concluded that there is a rising prevalence of dermatophytosis, with change in clinical presentation of infection. Although most of the therapeutic interventions show sufficient effect, there is a need for objective high-quality randomized comparative study to evaluate the effects of intervention, which can provide reliable evidence for clinical practice. Therefore, keeping this need in mind, we undertook this research work. To date, to the best of our knowledge, the inclusion of body surface area (BSA) as a tool for the evaluation of clinical improvement in dermatophytosis infection has not been considered. Objective The aim of this study was to assess the effect of topical antifungal as a monotherapy in naive and in combination with systemic antifungal drug in relapse cases of mild-to-moderate tinea corporis, to study and compare the efficacy of Clotrimazole 1% and Whitfield’s ointment as a monotherapy in mild-to-moderate cases of tinea corporis, and to study and compare the efficacy of combination of systemic terbinafine with Whitfield’s ointment and with clotrimazole 1% in mild-to-moderate relapsed cases of tinea corporis. Materials and Methods A total of 102 patients with mild-to-moderate tinea corporis who fulfilled the inclusion and exclusion criteria were enrolled. The naive patients for monotherapy and relapsed cases for a combination of systemic and topical antifungal drugs were randomly distributed. Results Predominance of males than females and the duration of disease for more than 6 weeks were observed. There was a significant reduction of infection in all the groups after 4 weeks, but early response was observed with clotrimazole as a monotherapy and in combination of clotrimazole with systemic drug. Conclusion Topical drugs as a monotherapy in naive and in combination of topical and systemic antifungal drug in relapsed cases were effective, but to achieve zero BSA, treatment for more than 4 weeks is required.

Conidiobolomycosis in Pediatric Patients

This review highlights the important features of conidiobolomycosis infection and describes its presentation in pediatric population. The importance of a broaden differential diagnosis to include fungal infections taking into account the geographical location and history of exposure. There is evidence of conidiobolomycosis affecting not only immunocompetent hosts but also more susceptible individuals that can present with atypical or systemic/disseminated disease, including children. Conidiobolomycosis is a rare fungal infection caused by species of the genera Conidiobolus. It affects skin and soft tissue mainly from nasal and face location, though atypical presentation which consists of orbital/eye/maxillary sinus involvement and disseminated/systemic disease can be present. These forms of disease are more frequent in children and immunocompromised/chronic patients. Diagnosis should be established with culture and histopathology. Treatment is not standardized, but combination of antifungal drugs with surgical interventions has shown highest efficacy.

Using Ultraviolet-A radiation and antifungals for treatment of dermatophytes isolated from cattle and farm workers

Dermatophytes are classified into 3 genera of fungi that commonly involve keratins tissue types; skin, nails and hairs in mammals. Ultraviolet radiation are used in the treatment of these fungi which cause DNA damage leading to inactivation of the pathogenic fungus. The present study was aimed to evaluate the ultraviolet (UV) radiation influence on the dermatophytes lesion growth that attack human and animal. Thirty isolates of dermatophytes were isolated from animals (skin scraping) and humans (skin scraping, hair and nail). Five species were identified viz., Trichophyton mentagrophyte, Trichophyton interdigitale, Trichophyton tonsurans, Trichophyton violaceum and Microsporum canis. UV-A, was found to be more active in delaying the dermatophytes colony growth in some current fungi widespread when combined with antifungal therapy to treat skin superficial fungal diseases, which caused dermatophytes lesion in human and animal. The present approach that a combination of antifungal drugs and UV-A to treat apparent dermatophytes diseases could reduce the therapeutic period and dosages which improve patients compliance.

Combination of Antifungal Drugs and Protease Inhibitors Prevent Candida albicans Biofilm Formation and Disrupt Mature Biofilms.

Biofilms formed by the fungal pathogen Candida albicans are resistant to many of the antifungal agents commonly used in the clinic. Previous reports suggest that protease inhibitors, specifically inhibitors of aspartyl proteases, could be effective antibiofilm agents. We screened three protease inhibitor libraries, containing a total of 80 compounds for the abilities to prevent C. albicans biofilm formation and to disrupt mature biofilms. The compounds were screened individually and in the presence of subinhibitory concentrations of the most commonly prescribed antifungal agents for Candida infections: fluconazole, amphotericin B, or caspofungin. Although few of the compounds affected biofilms on their own, seven aspartyl protease inhibitors inhibited biofilm formation when combined with amphotericin B or caspofungin. Furthermore, nine aspartyl protease inhibitors disrupted mature biofilms when combined with caspofungin. These results suggest that the combination of standard antifungal agents together with specific protease inhibitors may be useful in the prevention and treatment of C. albicans biofilm infections.

Clinical analysis of 69 cases of non-HIV-related cryptococcal meningitis

The clinical data of 69 patients with non-HIV-related cryptococcal meningitis admitted in the Second Hospital of Hebei Medical University from January 2013 to May 2019 were analyzed retrospectively.The main presentations of 69 patients are headache,fever,nausea,vomiting, visual impairment, hearing damage.Among them, 36 cases (52%) had underlying diseases, 30 cases (43%) were misdiagnosed, and 38 cases (55%) were complicated with high intracranial pressure. Cerebrospinal fluid examination showed that leukocytes increased in 47 cases, protein increased in 55 cases, chloride decreased in 41 cases, glucose decreased in 34 cases. The imaging findings were cerebral ischemia, hydrocephalus, meningeal or cerebral parenchyma enhancement. During the induction period, 63 cases were treated with combined antifungal drugs and 6 cases were treated with single antifungal drugs. The clinical symptoms were improved in 54 cases, 9 cases were discharged automatically and 6 cases died. The clinical manifestations, routine and biochemical examination of cerebrospinal fluid, imaging findings are not specific for patients with non-HIV-related cryptococcal meningitis.So early and multiple lumbar puncture should be performed to find etiological evidence to reduce misdiagnosis. The combination of antifungal drugs during the induction period is safe and effective. Key words: Meningitis,cryptococcal; Antifungal agents; Intracranial pressure; Neurosurgical procedures

In Vitro Evaluation of Antifungal Drug Combinations against Multidrug-Resistant Candida auris Isolates from New York Outbreak.

Since 2016, New York hospitals and health care facilities have faced an unprecedented outbreak of the pathogenic yeast Candida auris We tested over 1,000 C. auris isolates from affected facilities and found high resistance to fluconazole (MIC > 256 mg/liter) and variable resistance to other antifungal drugs. Therefore, we tested if two-drug combinations are effective in vitro against multidrug-resistant C. auris Broth microdilution antifungal combination plates were custom manufactured by TREK Diagnostic System. We used 100% inhibition endpoints for the drug combination as reported earlier for the intra- and interlaboratory agreements against Candida species. The results were derived from 12,960 readings, for 15 C. auris isolates tested against 864 two-drug antifungal combinations for nine antifungal drugs. Flucytosine (5FC) at 1.0 mg/liter potentiated the most combinations. For nine C. auris isolates resistant to amphotericin B (AMB; MIC ≥ 2.0 mg/liter), AMB-5FC (0.25/1.0 mg/liter) yielded 100% inhibition. Six C. auris isolates resistant to three echinocandins (anidulafungin [AFG], MIC ≥ 4.0 mg/liter; caspofungin [CAS], MIC ≥ 2.0 mg/liter; and micafungin [MFG], MIC ≥ 4.0 mg/liter) were 100% inhibited by AFG-5FC and CAS-5FC (0.0078/1 mg/liter) and MFG-5FC (0.12/1 mg/liter). None of the combinations were effective for C. auris 18-1 and 18-13 (fluconazole [FLC] > 256 mg/liter, 5FC > 32 mg/liter) except MFG-5FC (0.1/0.06 mg/liter). Thirteen isolates with a high voriconazole (VRC) MIC (>2 mg/liter) were 100% inhibited by the VRC-5FC (0.015/1 mg/liter). The simplified two-drug combination susceptibility test format would permit laboratories to provide clinicians and public health experts with additional data to manage multidrug-resistant C. auris.

The clinical case and treatment of seborrheic dermatitis and fingernails candidiasis

Today, mycotic lesions of the skin and their appendages are relevant and common throughout the world, taking first place in the structure of infectious pathology. Candidiasis of the skin, mucous membranes and nails is often found in the practice of a dermatologist, even among pediatric patients. The problem of treatment of candidiasis remains relevant, requires attention and continuous improvement of existing methods of treatment. For the treatment of candidiasis, the systemic antimycotic itraconazole (Itracon) has proven its efficiency, especially with damage to the nail plates. In this case, the best effect is achieved with a combination of systemic antifungal drugs and topical agents. Externally, antifungal varnish Cyclogen (cyclopirox 8 %) is used on the nail plates. In the complex treatment of nail candidiasis, the original Bion 3 probiotic-vitamin-mineral complex turned out to be effective.The article describes a clinical case and treatment of seborrheic dermatitis and candidiasis of fingernails. The complex treatment with levocetirizine (Alerzin) and 0.1 % mometasone furoate lotion (Elokom) is effective and safe for seborrheic dermatitis. When treating nail candidiasis, the systemic antimycotic itraconazole proved to be effective and safe in combination with Cyclogen (8 % cyclopirox) antifungal varnish. The introduction of the probiotic-vitamin-mineral complex Bion 3 in combination with the systemic antimycotic itraconazole and the antifungal varnish Cyclogen into the treatment complex of patients with nail candidiasis made it possible to improve the effectiveness of treatment, accelerate clinical and mycological recovery, reduce the duration of treatment, and prevent disease recurrence.

Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) Task Force against Recalcitrant Tinea (ITART) Consensus on the Management of Glabrous Tinea (INTACT).

Background and Aims:Dermatophytosis has always been a common superficial mycosis in India. However, the past 6-7 years have seen an unprecedented increase in the number of patients affected by recurrent, chronic, recalcitrant and steroid modified dermatophytosis involving the glabrous skin (tinea corporis, tinea cruris and tinea faciei). Importantly, there has been a notable decrease in clinical responsiveness to commonly used antifungals given in conventional doses and durations resulting in difficult-to-treat infections. Considering that scientific data on the management of the current epidemic of dermatophytosis in India are inadequate, the Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) Task force Against Recalcitrant Tinea (ITART) has formulated a consensus statement on the management of dermatophytosis in India.Methods:Seventeen dermatologists with a focussed interest in dermatophytosis participated in a Delphi consensus method, conducted in three rounds. They responded as either “agree” or “disagree” to 132 statements prepared by the lead experts and gave their comments. Consensus was defined as an agreement of 80% or higher concurrence. Statements on which there was no consensus were modified based on the comments and were then recirculated. The results were finally analysed in a face-to-face meeting and the responses were further evaluated. A draft of the consensus was circulated among the participants and modified based on their inputs.Results:Consensus was achieved on 90 of the 132 statements. Direct microscopy using potassium hydroxide mount was recommended in case of diagnostic difficulty on clinical examination. Counselling of patients about strict adherence to general measures and compliance to treatment was strongly recommended as the key to successful management of dermatophytosis. A combination of systemic and topical antifungal drugs was recommended for the treatment of glabrous tinea in the current scenario. Topical corticosteroid use, whether used alone or in combination with other components, was strongly discouraged by all the experts. It was suggested that topical antifungals may be continued for 2 weeks beyond clinical resolution. Itraconazole and terbinafine were recommended to be used as the first line options in systemic therapy, whereas griseofulvin and fluconazole are alternatives. Terbinafine was agreed to be used as a first line systemic agent in treatment naïve and terbinafine naïve patients with glabrous tinea. Regular follow-up of patients to ensure compliance and monitoring of clinical response was recommended by the experts, both during treatment and for at least 4 weeks after apparent clinical cure. Longer duration of treatment was recommended for patients with chronic, recurrent and steroid modified dermatophytosis.Conclusion:Consensus in the management of dermatophytosis is necessary in the face of conventional regimens proving ineffective and dearth of clinical trials re-evaluating the role of available antifungals in the wake of evolving epidemiology of the infection in the country. It needs to be backed by more research to provide the required level of evidence. It is hoped that this consensus statement improves the quality of care for patients with dermatophytosis, which has emerged as a huge public health problem, imposing considerable financial burden on the country.

Liposomal Amphotericin B Fosters the Corticosteroids' Anti-inflammatory Effect on Murine Allergic Bronchopulmonary Aspergillosis Model Airways.

Fungus is an antigen for bronchial asthma causing allergic bronchopulmonary mycosis (ABPM). As a therapy other than corticosteroids, itraconazole (ITCZ) is known to suppress the allergic inflammation induced by Aspergillus fumigatus (Af). However, the efficacy of liposomal amphotericin B (LAMB) with/without corticosteroid on ABPM is unknown. Mice sensitized to Dermatophagoides farinae (Df) allergen were intranasally infected with Af (DfAf group). After the infection, corticosteroid (dexamethasone (Dex)) was administered for 5days (DfAf/Dex group). The effects of ITCZ or LAMB with/without Dex were also evaluated. Pathologically, Dex and LAMB combination treatment decreased the allergic inflammation evidently. The bronchoalveolar lavage fluid (BALF) concentrations of IL-5, IL-13, and MIP-2 were significantly elevated in DfAf mice compared with control mice (p < 0.05, each). In DfAf mice, ITCZ and LAMB significantly decreased the elevation of MIP-2 (p < 0.05 vs the DfAf group). The addition of both Dex and LAMB suppressed the MIP-2 elevation in DfAf mice (p < 0.05 vs the Df/Af/Dex/LAMB group), but the addition of Dex and ITCZ did not (DfAf/Dex/ITCZ group). None of Dex, ITCZ, or LAMB decreased pulmonary IL-13 concentration. It was suggested that combination of antifungal drugs and corticosteroid enhanced the suppressing effect of airway inflammations. This finding will give a hope for the treatment of severe fungus-related asthma.

Oleic Acid Coated Silver Nanoparticles Showed Better in Vitro Amoebicidal Effects against Naegleria fowleri than Amphotericin B.

Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis (PAM) which almost always results in death. N. fowleri is also known as "brain-eating amoeba" due to its literal infestation of the brain leading to an inflammatory response in the brain tissues. Currently, there is no single drug that is available to treat PAM, and most treatments are combinations of antifungal, anticancer, and anti-inflammatory drugs. Recently nanotechnology has gained attention in chemotherapeutic research converging on drug delivery, while oleic acid (OA) has shown positive effects on the human immune system and inflammatory processes. In continuation of our recent research in which we reported the effects of oleic acid conjugated with silver nanoparticles (OA-AgNPs) against free-living amoeba Acanthamoeba castellanii, in this report, we show their antiamoebic effects against N. fowleri. OA alone and its nanoconjugates were tested against the amoeba by using amoebicidal and host cell cytopathogenicity assays. Trypan blue exclusion assay was used to determine cell viability. The results revealed that OA-AgNPs exhibited significantly enhanced antiamoebic effects (P < 0.05) against N. fowleri as compared to OA alone. Evidently, lactate dehydrogenase release shows reduced N. fowleri-mediated host cell cytotoxicity. Based on our study, we anticipate that further studies on OA-AgNPs could potentially provide an alternative treatment of PAM.

In vitro and in vivo Efficacy of a Synergistic Combination of Itraconazole and Verapamil Against Aspergillus fumigatus.

The incidence of aspergillosis continues to rise sharply, while the progress made in expanding the antifungal drug arsenal remains extremely slow, indicating an urgent need for new strategies. Previous studies have shown that the calcium signaling pathway, which is evolutionarily conserved in mammals and fungi, is involved in regulating the tolerance of azoles in fungi. In this study, we performed a preliminary screening among various combinations of different clinical calcium channel blockers and different antifungal drugs. We found that the combination of itraconazole and verapamil showed the best synergistic effect against Aspergillus fumigatus. Thereafter, using the checkboard assays we observed synergistic effects of the combination treatment against most of the A. fumigatus strains tested, including itraconazole-sensitive and itraconazole-resistant strains, with a fractional inhibitory concentration index (FICI) < 0.5. Furthermore, we showed that verapamil strongly decreased the cytosolic calcium transients following itraconazole stimulation by an aequorin-mediated method. Moreover, verapamil influenced the efflux of rhodamine 6G, an azole mimic substance. An ergosterol assay revealed that verapamil alone had no effect on ergosterol biosynthesis, but the combination of itraconazole and verapamil treatment decreased the ergosterol level. Further murine assays were performed using a luciferase-probed bioluminescence imaging method. Drug combination therapy reduced lung burden and improved survival rate. In conclusion, verapamil is a promising candidate to enhance the antifungal activity of itraconazole against A. fumigatus. In addition, our study suggests the effectiveness of an emerging approach based on bioluminescence imaging in monitoring the efficacy of drug combination therapy for invasive aspergillosis.

The Use of Galleria mellonella Larvae to Identify Novel Antimicrobial Agents against Fungal Species of Medical Interest.

The immune system of insects and the innate immune response of mammals share many similarities and, as a result, insects may be used to assess the virulence of fungal pathogens and give results similar to those from mammals. Larvae of the greater wax moth Galleria mellonella are widely used in this capacity and also for assessing the toxicity and in vivo efficacy of antifungal drugs. G. mellonella larvae are easy to use, inexpensive to purchase and house, and have none of the legal/ethical restrictions that are associated with use of mammals. Larvae may be inoculated by intra-hemocoel injection or by force-feeding. Larvae can be used to assess the in vivo toxicity of antifungal drugs using a variety of cellular, proteomic, and molecular techniques. Larvae have also been used to identify the optimum combinations of antifungal drugs for use in the treatment of recalcitrant fungal infections in mammals. The introduction of foreign material into the hemocoel of larvae can induce an immune priming effect which may operate independently with the activity of the antifungal drug. Procedures to identify this effect and limit its action are required.

Diagnostic Aspects of Veterinary and Human Aspergillosis.

The genus Aspergillus is composed of more than 300 species, a fraction of which are involved in animal or human infections mostly following environmental exposure. Various risk factors (i.e., immunosuppression, tuberculosis) have been recognized for human whereas for veterinary infections, unhygienic management, trauma, anatomical conformation of the skull, or suspected immunological deficiencies have been suggested. In animals, aspergillosis is mostly sporadic but in some circumstance such as infections on poultry farms may involve the whole flock. Since the high prevalence of immunosuppression in human patients has not been mirrored in veterinary medicine, and although to the best of our knowledge, no comprehensive data on the prevalence of aspergillosis in animals has been published, their epidemiology has not changed during the last decades. The impact of these infections may be economic or if they are incurable, sentimental. The objective of the first part is to describe the diagnosis of the main clinical entities caused by Aspergillus spp. in animals. It includes disseminated canine aspergillosis, canine and feline sino-nasal and sino-orbital aspergillosis, guttural pouch mycosis in horses, mycotic abortion in cattle, mycotic keratitis in horses, and avian aspergillosis. When pathogenesis and clinical aspects are relevant for diagnosis—they will be addressed as well. The second part deals with human aspergillosis, which is a multifaceted disease, manifested in a spectrum of clinical entities affecting one or more organs. Diagnosis is based on the clinical manifestation, supported and confirmed by laboratory means, involving the classical approach of demonstrating the etiological agent in the clinical specimens and in culture. Noncultural methods, such as antigen detection and/or molecular assays to detect fungal nucleic acids or protein profiles, are used as well. The isolation and identification of the fungus allows the determination of its susceptibility to antifungal drugs. Thus, antifungal susceptibility testing maybe considered as part of the diagnostic process, which is of relevance for management of the infection. In this review article, the part dealing with diagnostic aspects of aspergillosis in humans concentrates on susceptibility testing of Aspergillus spp. to antifungal drugs and drug combinations. The technologies and methods of susceptibility testing are described and evaluated.

Laser Therapies for Onychomycosis in Japan

Various treatment methods other than oral and topical antifungal medications have been employed to treat onychomycosis. Treatment methods include mechanical removal of the affected part of the nail plate by using a toenail cutter or grinder and chemical removal by using occlusive dressing therapy with salicylic acid plaster or urea cream. In recent years, laser therapies have received attention as modalities for treatment of onychomycosis. Favorable outcomes in patients with onychomycosis have been reported in Japan from treatment combining carbon dioxide laser and topical antifungal drug, treatment with photodynamic therapy, and treatment with Nd:YAG laser. However, irradiation conditions, number of irradiation sessions, and efficacy evaluation methods vary among institutions and studies; thus, there is no established evidence to support these outcomes. In addition, a study reported that a combination of Nd:YAG laser and external antifungal drugs was more effective than each of the treatments alone. Future studies are required to provide clinical evidence on the effectiveness of laser therapies, on the enhancement of effect from the combination of laser and external antifungal drugs, and on the possibility of shortening treatment duration using laser therapies in the management of patients with onychomycosis.

Фармакотерапия грибковых кератитов

The article presents a review of the literature on the various possibilities in application of antifungal drugs in the treatment of fungal keratitis. The fungal infection of the eye is one of the problems unsolved in the modern ophthalmology, which often leads not only to blindness, but to the loss of the eye as an organ. Despite decades of experience in the pharmacological treatment of fungal keratitis, the question of the officinal production of ophthalmic antifungal drugs has not yet been resolved. An ophthalmologist who has such patients is forced to search for resources available to him to provide medical care. As can be inferred from the literature, nowadays the drugs of first choice are natamycin, amphotericin B, fluconazole, and voriconazole. However, neither dosing nor modes of administration of these drugs are still standardized. It is also necessary to take into account possible side effects in their local and systemic application. Despite advances in the diagnosis and therapeutic treatment of mycotic keratitis, up to 27% of patients still require surgical interventions. But postoperative recurrences of the infection process can occur. More research (and closer attention from pharmaceutical companies) is needed to further investigate the routes of administration, concentrations and effective combinations of antifungal drugs as well as the improvement of the methods of diagnosing fungal infection.

Anti-Candida Activity of Biosurfactant Produced by Rhodotorula paludigena

Background: Biosurfactants are natural extracellular products that are produced by several microorganisms. These compounds are highly developed during recent years for industrial, medical, and environmental applications. Although, the majority of microbial biosurfactants were originated from bacterial species, some studies have shown that Rhodotorula muciliginosa and Candida rugosa are fungal sources for biosurfactants production. The aim of the present study was to evaluate anti- Candida activity of biosurfactant produced by R. paludigena. In addition, the combination of biosurfactant and several antifungal drugs was also investigated against Candida isolates. Materials and Methods: In the present study, R. paludigena was subjected for the production of biosurfactant and yielded product was confirmed using several specific tests. Biosurfactant was produced using Sabouraud dextrose broth at 29°C for 5-7 days. Cell-free supernatants were collected and extracted using chloroform-methanol solvent. Checkerboard microdilution method was used to assess antifungal susceptibility and combination interaction. Results: Out of 80 suspected isolates to Rhodotorula, only one strain (R. paludigena) has been found to be predominant for biosurfactant production. Our results show that produced biosurfactant has anti- Candida activity at the range of 1-8 mg/mL. Furthermore, it showed a synergistic effect with antifungal drugs caspofungin. Conclusion: It is concluded that R. paludigena has great potential for biosurfactant production with valuable antifungal effect against C. albicans. On the other hand, the synergistic effect was found when a combination of biosurfactant and caspofungin were applied against C. albicans. Keywords: Antifungal drugs, biosurfactant, Candida albicans, combination therapy, synergistic effect.

High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis

Cryptococcus spp., the causative agents of cryptococcosis, are responsible for deaths of hundreds of thousands of people every year worldwide. The drawbacks of available therapeutic options are aggravated by the increased resistance of yeast to the drugs, resulting in inefficient therapy. Also, the antifungal 5FC is not available in many countries. Therefore, a combination of antifungal drugs may be an interesting option, but in vitro and theoretical data point to the possible antagonism between the main antifungals used to treat cryptococcosis, i.e., fluconazole (FLC), and amphotericin B (AMB). Therefore, in vivo studies are necessary to test the above hypothesis. In this study, the efficacy of FLC and AMB at controlling C. gattii infection was evaluated in a murine model of cryptococcosis caused by C. gattii. The infected mice were treated with FLC + AMB combinations and showed a significant improvement in survival as well as reduced morbidity, reduced lung fungal burden, and the absence of yeast in the brain when FLC was used at higher doses, according to the Tukey test and principal component analysis. Altogether, these results indicate that combinatorial optimization of antifungal therapy can be an option for effective control of cryptococcosis.