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3 Biotech Jul 2023The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered... (Review)
Review
The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered by fungal species of the genera , , and . There have been cases of mucormycosis, aspergillosis, and candidiasis in COVID-19 patients. The treatments given to these opportunistic fungal infections include polyene like amphotericin B, azoles including imidazoles like ketoconazole, miconazole, and triazoles like fluconazole, voriconazole, itraconazole, Echinocandin derivatives like- caspofungin, micafungin, immunomodulatory therapy, granulocyte transfusion, etc. A successful recovery and the reduction of fatalities depend on prompt diagnosis and treatment. To reduce mortality, advanced techniques to identify such uncommon infections at a very early stage are necessary. This review's goal is to provide a summary of the systemic and superficial opportunistic fungal infections that the COVID-19 survivors were dealing with, including information on illness incidence, pathogenicity, and treatment.
PubMed: 37309405
DOI: 10.1007/s13205-023-03648-2 -
The Cochrane Database of Systematic... May 2015Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy.
OBJECTIVES
To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults.A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS.
SEARCH METHODS
We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials.
SELECTION CRITERIA
Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life.
DATA COLLECTION AND ANALYSIS
Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high.
MAIN RESULTS
We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies.Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another. KetoconazoleTopical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low-quality evidence) at four weeks of follow-up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I² = 74%). The median proportion of those who did not have clearance in the placebo groups was 69%.Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low-quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate-quality evidence).Ketoconozale yielded a similar remission failure rate as ciclopirox (RR 1.09, 95% CI 0.95 to 1.26, three studies, low-quality evidence). Most comparisons between ketoconazole and other antifungals were based on single studies that showed comparability of treatment effects. CiclopiroxCiclopirox 1% led to a lower failed remission rate than placebo at four weeks of follow-up (RR 0.79, 95% CI 0.67 to 0.94, eight studies, moderate-quality evidence) with similar rates of side effects (RR 0.9, 95% CI 0.72 to 1.11, four studies, moderate-quality evidence). Other antifungalsClotrimazole and miconazole efficacies were comparable with those of steroids on short-term assessment in single studies.Treatment effects on individual symptoms were less clear and were inconsistent, possibly because of difficulties encountered in measuring these symptoms.Evidence was insufficient to conclude that dose or mode of delivery influenced treatment outcome. Only one study reported on treatment compliance. No study assessed quality of life. One study assessed the maximum rash-free period but provided insufficient data for analysis. One small study in patients with HIV compared the effect of lithium versus placebo on seborrhoeic dermatitis of the face, but treatment outcomes were similar.
AUTHORS' CONCLUSIONS
Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class. Very few studies have assessed symptom clearance for longer periods than four weeks. Ketoconazole produced findings similar to those of steroids, but side effects were fewer. Treatment effect on overall quality of life remains unknown. Better outcome measures, studies of better quality and better reporting are all needed to improve the evidence base for antifungals for seborrhoeic dermatitis.
Topics: Adolescent; Adult; Antifungal Agents; Ciclopirox; Clotrimazole; Dermatitis, Seborrheic; Facial Dermatoses; Humans; Ketoconazole; Lithium Compounds; Miconazole; Pyridones; Randomized Controlled Trials as Topic; Scalp Dermatoses; Solanum; Steroids
PubMed: 25933684
DOI: 10.1002/14651858.CD008138.pub3 -
AMIA ... Annual Symposium Proceedings.... 2020The development of novel drugs in response to changing clinical requirements is a complex and costly method with uncertain outcomes. Postmarket pharmacovigilance is...
The development of novel drugs in response to changing clinical requirements is a complex and costly method with uncertain outcomes. Postmarket pharmacovigilance is essential as drugs often have under-reported side effects. This study intends to use the power of digital media to discover the under-reported side effects of marketed drugs. We have collected tweets for 11 different Drugs (Alprazolam, Adderall, Fluoxetine, Venlafaxine, Adalimumab, Lamotrigine, Quetiapine, Trazodone, Paroxetine, Metronidazole and Miconazole). We have compiled a vast adverse drug reactions (ADRs) lexicon that is used to filter health related data. We constructed machine learning models for automatically annotating the huge amount of publicly available Twitter data. Our results show that on average 43 known ADRs are shared between Twitter and FAERS datasets. Moreover, we were able to recover on average 7 known side effects from Twitter data that are not reported on FAERS. Our results on Twitter dataset show a high concordance with FAERS, Medeffect and Drugs.com. Moreover, we manually validated some of the under-reported side effect predicted by our model using literature search. Common known and under-reported side effects can be found at https://github.com/cbrl-nuces/Leveraging-digital-media-data-for-pharmacovigilance.
Topics: Diagnostic Tests, Routine; Drug-Related Side Effects and Adverse Reactions; Humans; Internet; Machine Learning; Pharmacovigilance; Social Media
PubMed: 33936417
DOI: No ID Found -
Journal of Obstetrics and Gynaecology :... Dec 2023At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a... (Review)
Review
At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a microsomal cytochrome P450 (CYP) enzyme. Imidazoles and triazoles impair the biosynthesis of ergosterol for the cytoplasmic membrane and lead to the accumulation of 14-α-methyl sterols. The synthetic imidazole miconazole is additionally able to increase intracellular reactive oxygen species, at least in part through inhibition of fungal catalase and peroxidase. This unique feature of miconazole is probably the basis for its fungicidal activity in , in addition to the fungistatic mode of action. Studies show that miconazole is superior to nystatin treatment and demonstrate its impact as one of the best options in managing vulvovaginal candidiasis. Regarding recurrent vulvovaginal candidiasis, several new drugs are currently developed to ensure effective treatment also for this group of patients.
Topics: Female; Humans; Miconazole; Candidiasis, Vulvovaginal; Antifungal Agents; Imidazoles; Nystatin; Candida albicans; Cytochrome P-450 Enzyme System
PubMed: 37029724
DOI: 10.1080/01443615.2023.2195001 -
International Journal of Molecular... May 2024Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new...
Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)AgNO], [(MTZ)Ag]SO, [Ag(MCZ)NO], [Ag(MCZ)BF], [Ag(MCZ)SbF] and [Ag(MCZ)ClO] (MTZ-metronidazole; MCZ-miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC values against the A375 line were demonstrated by [Ag(MCZ)NO] and [(MTZ)AgNO]. The compound [(MTZ)AgNO] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.
Topics: Humans; Melanoma; Miconazole; Silver; Antineoplastic Agents; Metronidazole; Cell Line, Tumor; Coordination Complexes; Cell Survival; Skin Neoplasms
PubMed: 38791121
DOI: 10.3390/ijms25105081 -
Journal of Ocular Pharmacology and... 2019Polyenes and azoles constitute 2 major drug classes in the antifungal armamentarium used to treat fungal infections of the eye such as fungal keratitis, endophthalmitis,... (Review)
Review
Polyenes and azoles constitute 2 major drug classes in the antifungal armamentarium used to treat fungal infections of the eye such as fungal keratitis, endophthalmitis, conjunctivitis, and blepharitis. These classes of drugs have come to occupy an important niche in ophthalmic antifungal therapy due to their broad spectrum of activity against a variety of filamentous and yeast-like fungi. Natamycin suspension (Natacyn), a polyene antifungal drug, is currently the only US FDA-approved formulation for treating ophthalmic fungal infections, whereas the other polyene and azole antifungals such as amphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, voriconazole, and posaconazole are routinely used off-label in the clinical setting. Despite potent antifungal activity, the clinical utility of these agents in ophthalmic infections has been challenged by their physicochemical properties, the unique ocular anatomy and physiology, selective antifungal activity, ocular and systemic toxicity, emergence of resistance and cross-resistance, and absence of reliable techniques for developing a robust in vitro-in vivo correlation. This review discusses the aforementioned challenges and the common approaches undertaken to circumnavigate the difficulties associated with the polyene- and azole-based pharmacotherapy of ophthalmic fungal infections.
Topics: Animals; Antifungal Agents; Azoles; Eye Infections, Fungal; Humans; Microbial Sensitivity Tests; Ophthalmic Solutions; Polyenes
PubMed: 30481082
DOI: 10.1089/jop.2018.0089 -
Journal of Fungi (Basel, Switzerland) Dec 2021In different regions worldwide, there exists an intra-and inter-regional variability in the rates of resistance to antifungal agents in , highlighting the importance of... (Review)
Review
In different regions worldwide, there exists an intra-and inter-regional variability in the rates of resistance to antifungal agents in , highlighting the importance of understanding the epidemiology and antifungal susceptibility profiles of in each region. However, in some regions, such as Ibero-America, limited data are available in this context. Therefore, in the present study, a systematic review was conducted to determine the antifungal resistance in in Ibero-America over the last five years. A literature search for articles published between January 2015 and December 2020 was conducted without language restrictions, using the PubMed, Embase, Cochrane Library, and LILACS databases. The search terms that were used were "" AND "antifungal resistance" AND "Country", and 22 publications were retrieved from different countries. The use of azoles (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, ketoconazole, and miconazole) varied between 4.0% and 100%, and that of echinocandins (micafungin, caspofungin, and anidulafungin) between 1.1% and 10.0%. The limited information on this subject in the region of Ibero-America emphasizes the need to identify the pathogens at the species level and perform antifungal susceptibility tests that may lead to the appropriate use of these drugs and the optimal doses in order to avoid the development of antifungal resistance or multi-resistance.
PubMed: 35049954
DOI: 10.3390/jof8010014 -
Polymers Nov 2022The development of semisolid formulations, gels in particular, has raised the attention of scientists more and more over the last decades. Because of their...
The development of semisolid formulations, gels in particular, has raised the attention of scientists more and more over the last decades. Because of their biocompatibility, hydrophilic nature, and capacity of absorbing large quantities of water, hydrogels are still one of the most promising pharmaceutical formulations in the pharmaceutical industry. The purpose of this study is to develop an optimal formulation capable of incorporating a water-poorly soluble active ingredient such as miconazole used in the treatment of fungal infections with and . A D-optimal design was applied to study the relationship between the formulation parameter and the gel characteristics. The independent parameters used in this study were the Carbopol 940 concentration (the polymer used to obtain the gel matrix), the sodium hydroxide amount, and the presence/absence of miconazole. Ten different dependent parameters (Y1-Y10) were evaluated (penetrometry, spreadability, viscosity, and tangential tension at 1 and 11 levels of speed whilst destructuring and during the reorganization of the gel matrix). The consistency of the gels ranged from 23.2 mm (GO2) to 29.6 mm (GM5). The least spreadable gel was GO7 (1384 mm), whilst the gel that presented the best spreadability was GO1 (3525 mm). The viscosity and the tangential stress at the selected levels (1 and 11) varied due to the different compositions of the proposed gels. The gels were also tested for drug content and antifungal activity. All determinations had satisfying results; the drug content was within limits accepted by Ph. Eur. 10 and all formulations containing miconazole exhibited antifungal activity. An optimal formulation with miconazole was attained, consisting of 0.84% Carbopol 940 and 0.32% sodium hydroxide.
PubMed: 36433136
DOI: 10.3390/polym14225011