-
The Cochrane Database of Systematic... Sep 2014Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Meta-Analysis)
Meta-Analysis Review
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 assess whether 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, itraconazole or voriconazole compared with placebo or no treatment in cancer patients with neutropenia.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.
MAIN RESULTS
Thirty-two trials involving 4287 patients were included. 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 with voriconazole. Amphotericin B and fluconazole decreased mortality ascribed to fungal infection (RR 0.45, 95% CI 0.26 to 0.76 and RR 0.42, 95% CI 0.24 to 0.73, respectively). The incidence of invasive fungal infection decreased significantly with administration of amphotericin B (RR 0.41, 95% CI 0.24 to 0.73), 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 to allow a meaningful overview. For the 2011 and 2014 updates no additional trials were identified for inclusion.
AUTHORS' CONCLUSIONS
Intravenous amphotericin B was the only antifungal agent that reduced total mortality. It should therefore be preferred when prophylactic or empirical antifungal therapy is introduced in cancer patients with neutropenia.
Topics: Antifungal Agents; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Randomized Controlled Trials as Topic
PubMed: 25188768
DOI: 10.1002/14651858.CD000026.pub2 -
Cureus Oct 2022Otomycosis is a disease whose acute form affects four in 1,000 persons annually and the chronic form affects 3-5% of the population. It is brought on by various fungi,... (Review)
Review
Otomycosis is a disease whose acute form affects four in 1,000 persons annually and the chronic form affects 3-5% of the population. It is brought on by various fungi, primarily saprophytes which most commonly include the Candida albicans and Aspergillus niger. The disease rarely poses a life-threatening danger, but as it requires prolonged treatment and follow-up and has a significant chance of recurrence, it has a difficult and taxing course. Numerous therapeutic modalities are available for the treatment of otomycosis. In the beginning, the fungal elements are removed by ear toilet - washing or suctioning of the ear canal followed by drying. Topical therapy includes the use of antifungals, of which the most commonly used drugs include clotrimazole or miconazole, often given along with ceftazidime which is an antibacterial. The primary mechanism by which clotrimazole works is by impairing the permeability barrier of the cytoplasmic membrane of the fungi, which causes holes to appear in the cell membrane and leaking out of the contents of the organism, thus killing the fungus and treating the infection. Various studies suggest that following clotrimazole drop therapy, symptoms suggestive of otomycosis are not at risk for recurrence of the disease and due to its economical pricing and easy availability, is frequently recommended by otolaryngologists in the treatment of otomycosis. In this review article, we will discuss about the effectiveness of the drug in different populations, observe treatment failures and relapse of the disease, analyze the ability of clotrimazole drops in preventing relapse of the infection, and observe the role of the drug in reducing the signs and symptoms of the disease.
PubMed: 36381881
DOI: 10.7759/cureus.30098 -
Heliyon Aug 2023Due to the adverse effects associated with long-term administration of antifungal drugs used for treating dermatophytic lesions like tinea unguium, there is a critical... (Review)
Review
Due to the adverse effects associated with long-term administration of antifungal drugs used for treating dermatophytic lesions like tinea unguium, there is a critical need for novel antifungal therapies that exhibit improved absorption and minimal adverse effects. Nanoformulations offer a promising solution in this regard. Topical formulations may penetrate the upper layers of the skin, such as the stratum corneum, and release an appropriate amount of drugs in therapeutic quantities. Liposomes, particularly nanosized ones, used as topical medication delivery systems for the skin, may have various roles depending on their size, lipid and cholesterol content, ingredient percentage, lamellarity, and surface charge. Liposomes can enhance permeability through the stratum corneum, minimize systemic effects due to their localizing properties, and overcome various challenges in cutaneous drug delivery. Antifungal medications encapsulated in liposomes, including fluconazole, ketoconazole, croconazole, econazole, terbinafine hydrochloride, tolnaftate, and miconazole, have demonstrated improved skin penetration and localization. This review discusses the traditional treatment of dermatophytes and liposomal formulations. Additionally, promising liposomal formulations that may soon be available in the market are introduced. The objective of this review is to provide a comprehensive understanding of dermatophyte infections and the role of liposomes in enhancing treatment.
PubMed: 37583758
DOI: 10.1016/j.heliyon.2023.e18960 -
The Cochrane Database of Systematic... Nov 2017Vulvovaginal candidiasis (VVC) is estimated to be the second most common form of infection after bacterial vaginosis. The ability of probiotics in maintaining and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vulvovaginal candidiasis (VVC) is estimated to be the second most common form of infection after bacterial vaginosis. The ability of probiotics in maintaining and recovering the normal vaginal microbiota, and their potential ability to resist Candidas give rise to the concept of using probiotics for the treatment of VVC.
OBJECTIVES
To assess the effectiveness and safety of probiotics for the treatment of vulvovaginal candidiasis in non-pregnant women.
SEARCH METHODS
We searched the following databases to October 2017: Sexually Transmitted Infections Cochrane Review Group's Specialized Register, CENTRAL, MEDLINE, Embase and eight other databases. We searched in following international resources: World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, Web of Science and OpenGrey. We checked specialty journals, reference lists of published articles and conference proceedings. We collected information from pharmaceutical companies and experts in the field.
SELECTION CRITERIA
Randomized controlled trials (RCT) using probiotics, alone or as adjuvants to conventional antifungal drugs, to treat VVC in non-pregnant women. Trials recruiting women with recurrent VVC, coinfection with other vulvovaginal infections, diabetes mellitus, immunosuppressive disorders or taking immunosuppressant medication were ineligible for inclusion. Probiotics were included if they were made from single or multiple species and in any preparation type/dosage/route of administration.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility and quality and extracted data. We resolved any disagreements through consensus. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS
Ten RCTs (1656 participants) met our inclusion criteria, and pharmaceutical industry funded none of these trials. All trials used probiotics as adjuvant therapy to antifungal drugs. Probiotics increased the rate of short-term clinical cure (risk ratio (RR) 1.14, 95% confidence interval (CI) 1.05 to 1.24, 695 participants, 5 studies, low quality evidence) and mycological cure (RR 1.06, 95% CI 1.02 to 1.10, 969 participants, 7 studies, low quality evidence) and decreased relapse rate at one month (RR 0.34, 95% CI 0.17 to 0.68, 388 participants, 3 studies, very low quality evidence). However, this effect did not translate into a higher frequency of long-term clinical cure (one month after treatment: RR 1.07, 95% CI 0.86 to 1.33, 172 participants, 1 study, very low quality evidence; three months after treatment: RR 1.30, 95% CI 1.00 to 1.70, 172 participants, one study, very low quality evidence) or mycological cure (one month after treatment: RR 1.26, 95% CI 0.93 to 1.71, 627 participants, 3 studies, very low quality evidence; three months after treatment: RR 1.16, 95% CI 1.00 to 1.35, 172 participants, one study, very low quality evidence). Probiotics use did not increase the frequency of serious (RR 0.80, 95% CI 0.22 to 2.94; 440 participants, 2 studies, low quality evidence). We found no eligible RCTs for outcomes as time to first relapse, need for additional treatment at the end of therapy, patient satisfaction and cost effectiveness.
AUTHORS' CONCLUSIONS
Low and very low quality evidence shows that, compared with conventional treatment, the use of probiotics as an adjuvant therapy could increases the rate of short-term clinical and mycological cure and decrease the relapse rate at one month but this did not translate into a higher frequency of long-term clinical or mycological cure. Probiotics use does not seem to increase the frequency of serious or non-serious adverse events. There is a need for well-designed RCTs with standardized methodologies, longer follow-up and larger sample size.
Topics: Administration, Intravaginal; Antifungal Agents; Candidiasis, Vulvovaginal; Clotrimazole; Female; Fluconazole; Humans; Imidazoles; Miconazole; Probiotics; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 29168557
DOI: 10.1002/14651858.CD010496.pub2 -
The Cochrane Database of Systematic... May 2021Otomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Otomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole group ('azoles') being among the most widely used.
OBJECTIVES
To evaluate the benefits and harms of topical azole treatments for otomycosis.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 11 November 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in adults and children with otomycosis comparing any topical azole antifungal with: placebo, no treatment, another type of topical azole or the same type of azole but applied in different forms. A minimum follow-up of two weeks was required.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were: 1) clinical resolution as measured by the proportion of participants with complete resolution at between two and four weeks after treatment (however defined by the authors of the studies) and 2) significant adverse events. Secondary outcomes were 3) mycological resolution and 4) other less serious adverse effects. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included four studies with 559 participants from Spain, Mexico and India. Three studies included children and adults; one included only adults. The duration of symptoms was not always explicitly stated. Mycological resolution results were only reported in one study. The studies assessed two comparisons: one type of topical azole versus another and the same azole but administered in different forms (cream versus solution). A. Topical azoles versus placebo None of the studies assessed this comparison. B. Topical azoles versus no treatment None of the studies assessed this comparison. C. One type of topical azole versus another type of topical azole i) Clotrimazole versus other types of azoles (eberconazole, fluconazole, miconazole) Three studies examined clotrimazole versus other types of azoles. The evidence is very uncertain about the difference between clotrimazole and other types of azole in achieving complete clinical resolution at four weeks (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.07; 3 studies; 439 participants; very low-certainty evidence). The anticipated absolute effects are 668 per 1000 for clotrimazole versus 835 per 1000 for other azoles. One study planned a safety analysis and reported no significant adverse events in either group. The evidence is therefore very uncertain about any differences between clotrimazole and other types of azole (no events in either group; 1 study; 174 participants; very low-certainty evidence). Clotrimazole may result in little or no difference in mycological resolution at two weeks follow-up (RR 1.01, 95% CI 0.96 to 1.06; 1 study; 174 participants; low-certainty evidence) or in other (less serious) adverse events at two weeks follow-up (36 per 1000, compared to 45 per 1000, RR 0.79, 95% CI 0.18 to 3.41; 1 study; 174 participants; very low-certainty evidence). ii) Bifonazole cream versus bifonazole solution One study compared bifonazole 1% cream with solution. Bifonazole cream may have little or no effect on clinical resolution at two weeks follow-up when compared to solution, but the evidence is very uncertain (RR 1.07, 95% CI 0.73 to 1.57; 1 study; 40 ears; very low-certainty evidence). Bifonazole cream may achieve less mycological resolution compared to solution at two weeks after the end of therapy, but the evidence for this is also very uncertain (RR 0.53, 95% CI 0.29 to 0.96; 1 study; 40 ears; very low-certainty evidence). Five out of 35 patients sustained severe itching and burning from the bifonazole solution but none with the bifonazole cream (very low-certainty evidence).
AUTHORS' CONCLUSIONS
We found no studies that evaluated topical azoles compared to placebo or no treatment. The evidence is very uncertain about the effect of clotrimazole on clinical resolution of otomycosis, on significant adverse events or other (non-serious) adverse events when compared with other topical azoles (eberconazole, fluconazole, miconazole). There may be little or no difference between clotrimazole and other azoles in terms of mycological resolution. It may be difficult to generalise these results because the range of ethnic backgrounds of the participants in the studies is limited.
Topics: Administration, Topical; Adult; Antifungal Agents; Bias; Child; Clotrimazole; Cycloheptanes; Fluconazole; Humans; Imidazoles; Miconazole; Otomycosis; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34033120
DOI: 10.1002/14651858.CD009289.pub2 -
Iranian Journal of Otorhinolaryngology Jan 2022Fungal otitis extern or otomycosis, is common worldwide, and resistance of fungal organisms to antifungal drugs has been reported in otomycosis and other fungal...
INTRODUCTION
Fungal otitis extern or otomycosis, is common worldwide, and resistance of fungal organisms to antifungal drugs has been reported in otomycosis and other fungal infections. This study aimed to evaluate the clinical efficacy of sertaconazole versus placebo, as well as miconazole and clotrimazole topical creams in otomycosis patients.
MATERIALS AND METHODS
In this double-blinded clinical trial, 138 otomycosis patients (230 ears) were evaluated in four groups. After the first session of the ear canal debridement and irrigation with acetic acid 2% solution, the patients were treated with either A) sertaconazole 2% cream, B) miconazole 2% cream, C) clotrimazole 2% cream, or D) placebo. The results of clinical evaluations and response to treatment (complete, partial, and no response) were recorded at the time of the first visit and by the end of the first, second, and fourth weeks of treatment. A p-value less than 0.05 was considered statistically significant.
RESULTS
Response results to treatments, ear itching, aural fullness, otalgia, and otorrhea revealed significant differences in either group A or groups B and C, compared to the placebo group (P<0.05). Considering both complete and partial responses together, the sertaconazole group showed a 96.43% response rate. For complete response, miconazole revealed better results, compared to the other two creams; however, the differences for the therapeutic outcomes were not statistically significant. No adverse reactions were observed in the study groups.
CONCLUSIONS
Sertaconazole had comparable results with miconazole and clotrimazole in the treatment of otomycosis, and especially if complete and partial responses were considered together, it was more efficacious than miconazole and clotrimazole creams.
PubMed: 35145933
DOI: 10.22038/IJORL.2021.54805.2872 -
Brazilian Journal of Microbiology :... Mar 2022Staphylococcus aureus is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant S. aureus strains, there is a need for...
Staphylococcus aureus is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant S. aureus strains, there is a need for new drugs discovery. Due to the poor supply of new antimicrobials, targeting virulence of S. aureus may generate weaker selection for resistant strains, anti-virulence agents disarm the pathogen instead of killing it. In this study, the ability of the FDA-approved drugs domperidone, candesartan, and miconazole as inhibitors of S. aureus virulence was investigated. The effect of tested drugs was evaluated against biofilm formation, lipase, protease, hemolysin, and staphyloxanthin production by using phenotypic and genotypic methods. At sub-inhibitory concentrations, candesartan, domperidone, and miconazole showed a significant inhibition of hemolysin (75.8-96%), staphyloxanthin (81.2-85%), lipase (50-65%), protease (40-64%), and biofilm formation (71.4-90%). Domperidone and candesartan have similar activity and were more powerful than miconazole against S. aureus virulence. The hemolysins and lipase inhibition were the greatest under the domperidone effect. Candesartan showed a remarkable reduction in staphyloxanthin production. The highest inhibitory effect of proteolytic activity was obtained with domperidone and candesartan. Biofilm was significantly reduced by miconazole. Expression levels of crtM, sigB, sarA, agrA, hla, fnbA, and icaA genes were significantly reduced under candesartan (68.98-82.7%), domperidone (62.6-77.2%), and miconazole (32.96-52.6%) at sub-MIC concentrations. Candesartan showed the highest inhibition activity against crtM, sigB, sarA, agrA, hla, and icaA expression followed by domperidone then miconazole. Domperidone showed the highest downregulation activity against fnbA gene. In conclusion, candesartan, domperidone, and miconazole could serve as anti-virulence agents for attenuation of S. aureus pathogenicity.
Topics: Anti-Bacterial Agents; Benzimidazoles; Biofilms; Biphenyl Compounds; Domperidone; Humans; Methicillin-Resistant Staphylococcus aureus; Miconazole; Staphylococcal Infections; Staphylococcus aureus; Tetrazoles; Virulence
PubMed: 34773629
DOI: 10.1007/s42770-021-00655-4 -
European Journal of Pharmaceutical... Sep 2023Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy...
Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy of the vulvovaginal candidiasis (VVC). They were synthesized by emulsification and solvent evaporation techniques, characterized by diameter, polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy (AFM), evaluated in terms of efficacy against C. albicans in vitro, and tested in a murine VVC model. Nanoparticles showed 211nm of diameter with a 0.32 polydispersity index, -53mV of zeta potential, and 90% miconazole encapsulation efficiency. AFM evidenced nanoparticles with a spherical shape. They inhibited the proliferation of C. albicans in vitro and in vivo after a single administration. Nanoparticles released the miconazole directly in the site of action at low therapeutic doses, which was enough to eliminate the fungal burden in the murine VVC model. These systems were rationally designed since the existence of the HA induces their adhesion on the vaginal mucus and their internalization via CD44 receptors, inhibiting the C. albicans. Therefore, miconazole-loaded nanoparticles/HA represent an innovative non-conventional pharmaceutical dosage form to treat the VVC and recurrent VVC.
Topics: Humans; Female; Mice; Animals; Miconazole; Candidiasis, Vulvovaginal; Hyaluronic Acid; Antifungal Agents; Candida albicans; Nanoparticles
PubMed: 37379779
DOI: 10.1016/j.ejps.2023.106508 -
Iranian Journal of Public Health Apr 2022a species are normal vaginal flora in healthy women, which can cause vulvovaginal candid-iasis (VVC). The formation of biofilm is a cause of drug resistance in species...
BACKGROUND
a species are normal vaginal flora in healthy women, which can cause vulvovaginal candid-iasis (VVC). The formation of biofilm is a cause of drug resistance in species of vaginal origin. We aimed to specify species cause VVC, detect their biofilm-forming ability, and antifungal susceptibility pattern.
METHODS
Overall 150 vaginal samples were collected from suspected cases of referring to Bahar Hospital of Shahroud, Iran between Jan 2018 and Jan 2019. Samples were cultured on Sabouraud dextrose agar (SDA), Chrome gar and Corn meal agar (CMA). PCR-RFLP was performed to confirm the identification. Bio-film formation of the identified species was measured by the Crystal Violet method. The susceptibility to fluconazole, clotrimazole, and miconazole was determined based on the CLSI document M27-A3.
RESULTS
Of 50 women (33.3%) were suffering from VVC. was the predominant species isolated in this study (n=39, 78%) followed by (n=11, 22%). In addition, in 25 (50%) of positive samples, bio-film formation was determined. The mean MIC of fluconazole and clotrimazole for was 5.02 μg/mL and 3.92 μg/mL, respectively. Furthermore, the mean MIC related to these drugs for was 12.45 μg / mL and 4.1μg / mL, respectively. The mean diameter of miconazole inhibition zone for and isolates was 25.13 mm and 24.5mm, respectively and all of them were susceptible to this drug.
CONCLUSION
was the predominant species isolated from patients with VVC and also was the predominant biofilm producer species.
PubMed: 35936523
DOI: 10.18502/ijph.v51i4.9253 -
Saudi Pharmaceutical Journal : SPJ :... Apr 2023Miconazole is a synthetic derivative of imidazole, a medication with a broad-spectrum antifungal agent that is used to treat localized vaginal, skin, and nail...
Miconazole is a synthetic derivative of imidazole, a medication with a broad-spectrum antifungal agent that is used to treat localized vaginal, skin, and nail infections. The aim of the study was to develop an innovative technique to improve the permeability and efficacy of topical miconazole nitrate. A nanoemulgel of miconazole nitrate was formulated by the incorporation of a nanoemulsion and a hydrogel. The nanoemulsion was first optimized using a self-emulsifying technique, and the drug was then loaded into the optimum formulation and evaluated prior to mixing with the hydrogel. Miconazole nitrate nanoemulgel formulations were evaluated for their physical characteristics and antifungal activity. Based on the results, the formulation with 0.4 % Carbopol showed the highest release profile (41.8 mg/ml after 2 h); thus, it was chosen as the optimum formulation. A cell diffusion test was performed to examine the ability of the Miconazole nitrate nanoemulgel to penetrate the skin and reach the bloodstream. Percentage cumulative drug releases of 29.67 % and 23.79 % after 6 h were achieved for the MNZ nanoemulgel and the commercial cream, Daktazol, respectively. The antifungal activity of the novel MNZ nanoemulgel formulation was tested against and compared to Daktazol cream and almond oil; the results were: 40.9 ± 2.3 mm, 25.4 ± 2.7 mm and 18 ± 1.9 mm, respectively. In conclusion, a novel MNZ nanoemulgel showing superior antifungal activity compared to that of the commercial product has been developed. This nanotechnology technique is a step toward making pharmaceutical dosage forms that has a lot of promise.
PubMed: 37063448
DOI: 10.1016/j.jsps.2023.02.005