Potential Sexual Transmission of Antifungal-Resistant Trichophyton indotineae.

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.

Recognition of Antifungal-Resistant Dermatophytosis by Infectious Diseases Specialists, United States.

Antifungal-resistant dermatophyte infections have recently emerged as a global public health concern. A survey of US infectious diseases specialists found that only 65% had heard of this issue and just 39% knew how to obtain testing to determine resistance. Increased clinician awareness and access to testing for antifungal-resistant dermatophytosis are needed.

Analogs of the anti-malaria drug mefloquine have broad-spectrum antifungal activity and are efficacious in a model of disseminated Candida auris infection.

Only three classes of antifungal drugs are currently in clinical use. Here, we report that derivatives of the malarial drug mefloquine have broad-spectrum antifungal activity including difficult-to-treat molds and endemic fungi. Pharmacokinetic and efficacy studies of NSC-4377 indicate that it penetrates the central nervous system and is active against Candida auris in vivo. These data strongly support the further development of mefloquine analogs as a potentially new class of antifungal molecules.

Bimodal distribution of azole susceptibility in Sporothrix brasiliensis isolates in Brazil.

Sporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phylogenetic analysis found the in vitro resistant isolates were not clonal and were distributed across three different S. brasiliensis clades. Single nucleotide polymorphism (SNP) analysis was performed to identify potential mechanisms of in vitro resistance. Two of the 28 resistant isolates (MIC ≥16 mg/L) had a polymorphism in the cytochrome P450 gene, cyp51, corresponding to the well-known G448S substitution inducing azole resistance in Aspergillus fumigatus. SNPs corresponding to other known mechanisms of azole resistance were not identified in the remaining 26 in vitro resistant isolates.

A population pharmacokinetic model for posaconazole intravenous solution and oral powder for suspension formulations in pediatric patients with neutropenia.

The objective of this study was to support posaconazole dose regimens in pediatric patients aged ≥2 years, using a population pharmacokinetic (PK) approach with data from a phase 1b study (NCT02452034). A one-compartment model with first-order absorption was fit to pharmacokinetic data from 144 participants aged 2 to 17 years, who were administered posaconazole as intravenous (IV) and powder for oral suspension (PFS) formulations, or IV only, at dosing regimens of 3.5, 4.5, and 6 mg/kg. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backward exclusion procedure. The final model simulated posaconazole exposure in patients aged 2 to <7 and 7 to 17 years at dosing regimens of 4.5, 6, and 7.5 mg/kg. Plasma concentration data following IV and PFS administration were well-described by a one-compartment model with first-order absorption and estimated bioavailability, where clearance and volume were subject to allometric scaling by body weight. The 6-mg/kg dosing regimen achieved the pharmacokinetic target (90% of the pediatric population having an average steady-state plasma concentration of ≥500 and <2,000 ng/mL) for both age groups, regardless of whether patients received IV and PFS or IV only. In a virtual adolescent population (body weight >40 kg), the 300 mg/day posaconazole tablet was also predicted to achieve the pharmacokinetic target and remain within a safe range of exposure. These data informed a weight-based nomogram for PFS dosing to maximize the number of pediatric patients achieving the pharmacokinetic target across weight bands, while also maintaining a favorable benefit/risk profile.

Case Commentary: Extending our therapeutic range against multidrug-resistant Candida.

Deep-seated Candida spp. infections may necessitate extended durations of antifungal therapy. Increasing resistance to first-line antifungals threatens the most common options for long-term treatment. In this issue, Ponta et al. (Antimicrob Agents Chemother 68:e00750-24, 2024, https://doi.org/10.1128/aac.00750-24) present cases in which they used rezafungin, a novel long-acting echinocandin antifungal, for extended durations. While excellent clinical evidence supports the short-term safety of rezafungin, these cases demonstrate that rezafungin may additionally have a role in long-term suppressive therapy for antifungal-resistant Candida spp. infections.

In vitro activity of ibrexafungerp against clinically relevant echinocandin-resistant Candida strains.

Invasive candidiasis is a major hospital-acquired infection. Usually, echinocandins are considered first-line treatment. However, resistant phenotypes have emerged. Ibrexafungerp (IBX) is a new antifungal substance with potent anti-Candida activity. We challenged IBX with a library of 192 pheno-/genotypically echinocandin-resistant Candida isolates, focusing on the substance susceptibility, its activity on certain FKS hotspot (HS) mutated strains, and applying WTULs (wild-type upper limits). Therefore, a 9-year-old strain and patient data collection provided by the German National Reference Center for Invasive Fungal Infections were analyzed. Species identification was confirmed through ITS-sequencing. Molecular susceptibility testing was performed by sequencing HS of the FKS gene. Anidulafungin (AND) and IBX EUCAST-broth-microdilution was conducted. The four most common echinocandin-resistance mediating mutations were found in Candida glabrata [112/192 isolates; F659-(43×) and S663-(48×)] and Candida albicans [63/192 isolates; F641-(15×) and S645-(39×)]. Mutations at the HS-start sequence were associated with higher IBX MIC-values (F659 and F641 (MIC 50/90 mg/L: >4/>4 and 2/4 mg/L) in comparison to AND (F659 and F641 (MIC 50/90: 1/4 and 0.25/1 mg/L). MIC-values in HS-center mutations were almost equal [MIC50/90 in S663: 2/4 (AND and IBX); in S645: 0.5/1 (AND) and 0.25/1 (IBX) mg/L]. In total, 61 vs 78 of 192 echinocandin-resistant isolates may be classified as IBX wild type by applying WTULs, whereas the most prominent effect was seen in C. albicans [48% (30/63) vs 70% (44/63)]. IBX shows in vitro activity against echinocandin-resistant Candida and thus is an addition to the antifungal armory. However, our data suggest that this effect is more pronounced in C. albicans and strains harboring mutations, affecting the HS-center.

Shining a light on the impact of antifungals on Aspergillus fumigatus subcellular dynamics through fluorescence imaging.

Fluorescent proteins (FPs) are indispensable tools used for molecular imaging, single-cell dynamics, imaging in infection models, and more. However, next-generation FPs have yet to be characterized in Aspergillus. Here, we characterize 18 FPs in the pathogenic filamentous fungus Aspergillus fumigatus spanning the visible light spectrum. We report on in vivo FP brightness in hyphal and spore morphotypes and show how a fluoropyrimidine-based selection system can be used to iteratively introduce four distinct FPs enabling the simultaneous visualization of the cell membrane, mitochondria, peroxisomes, and vacuoles. Using this strain, we describe and compare the dynamic responses of organelles to stresses induced by voriconazole, amphotericin B, and the novel antifungal drugs olorofim and manogepix. The expansion to the fluorescent genetic toolbox will overcome boundaries in research applications that involve fluorescence imaging in filamentous fungi.

Efficacy of an oral lipid nanocrystal formulation of amphotericin B (MAT2203) in the neutropenic mouse model of pulmonary mucormycosis.

Invasive mucormycosis (IM) is associated with high mortality and morbidity. MAT2203 is an orally administered lipid nanocrystal formulation of amphotericin B, which has been shown to be safe and effective against other fungal infections. We sought to compare the efficacy of MAT2203 to liposomal amphotericin B (LAMB) treatment in a neutropenic mouse model of IM due to Rhizopus arrhizus var. delemar or Mucor circinelloides f. jenssenii DI15-131. In R. arrhizus var. delemar-infected mice, 15 mg/kg of MAT2203 qd was as effective as 10 mg/kg of LAMB in prolonging median survival time vs placebo (13.5 and 16.5 days for MAT2203 and LAMB, respectively, vs 9 days for placebo) and enhancing overall survival vs placebo-treated mice (40% and 45% for MAT2203 and LAMB, respectively, vs 0% for placebo). A higher dose of 45 mg/kg of MAT2203 was not well tolerated by mice and showed no benefit over placebo. Similar results were obtained with mice infected with M. circinelloides. Furthermore, while both MAT2203 and LAMB treatment resulted in a significant reduction of ~1.0-2.0log and ~2.0-2.5log in Rhizopus delemar or M. circinelloides lung and brain burden vs placebo mice, respectively, LAMB significantly reduced tissue fungal burden in mice infected with R. delemar vs tissues of mice treated with MAT2203. These results support continued investigation and development of MAT2203 as a novel and oral formulation of amphotericin for the treatment of mucormycosis.

Metagenomic exploration of the rhizosphere soil microbial community and their significance in facilitating the development of wild-simulated ginseng.

Panax ginseng, a prized medicinal herb, has faced increasingly challenging field production due to soil degradation and fungal diseases in Northeast China. Wild-simulated cultivation has prevailed because of its sustainable soil management and low disease incidence. Despite the recognized benefits of rhizosphere microorganisms in ginseng cultivation, their genomic and functional diversity remain largely unexplored. In this work, we utilized shotgun metagenomic analysis to reveal that Pseudomonadota, Actinomycetota, and Acidobacteriota were dominant in the ginseng rhizobiome and recovered 14 reliable metagenome-assembled genomes. Functional analysis indicated an enrichment of denitrification-associated genes, potentially contributing to the observed decline in soil fertility, while genes associated with aromatic carbon degradation may be linked to allelochemical degradation. Further analysis demonstrated enrichment of Actinomycetota in 9-year-old wild-simulated ginseng (WSG), suggesting the need for targeted isolation of Actinomycetota bacteria. Among these, at least three different actinomycete strains were found to play a crucial role in fungal disease resistance, with Streptomyces spp. WY144 standing out for its production of actinomycin natural products active against the pathogenic fungus Ilyonectria robusta. These findings not only enhance our understanding of the rhizobiome of WSG but also present promising avenues for combating detrimental fungal pathogens, underscoring the importance of ginseng in both medicinal and agricultural contexts.IMPORTANCEWild-simulated ginseng, growing naturally without human interference, is influenced by its soil microbiome. Using shotgun metagenomics, we analyzed the rhizospheric soil microbiome of 7- and 9-year-old wild-simulated ginseng. The study aimed to reveal its composition and functions, exploring the microbiome's key roles in ginseng growth. Enrichment analysis identified Streptomycetes in ginseng soil, with three strains inhibiting plant pathogenic fungi. Notably, one strain produced actinomycins, suppressing the ginseng pathogenic fungus Ilyonectria robusta. This research accelerates microbiome application in wild-simulated ginseng cultivation, offering insights into pathogen protection and supporting microbiome utilization in agriculture.

Increasing rate of non-Candida albicans yeasts and fluconazole resistance in yeast isolates from women with recurrent vulvovaginal candidiasis in Leeds, United Kingdom.

OBJECTIVES: Azoles have been the mainstay of recurrent vulvovaginal candidiasis (RVVC) for many years. Because of a recent anecdotal increase in non-Candida albicans yeasts (NCAY) and azole-resistant C. albicans cases, their prevalence was calculated from cultures for yeasts in women with complicated/RVVC over 3 years. METHODS: Retrospective data search of vaginal cultures from adult women in Leeds, UK between April 2018 and March 2021 was conducted. Samples with clinical details of complicated/RVVC had full yeast identification and antifungal susceptibility performed. Differences in prevalence between 12-month periods were determined using χ2 tests. RESULTS: Over the 3 years, cultures were performed on 5461 vaginal samples from women with clinical information indicating they had complicated/RVVC, RVVC, with 1828 (33.5%) growing yeasts.Over 85% of yeasts each year were C. albicans, however the proportion declined yearly with an increase in NCAY species. Nakaseomyces glabrata was the most frequent NCAY species isolated, increasing from 2.8% in 2018-19 to 6.8% in 2020-21. Total NCAY species increased from 6.0% in 2018-19 to 12.6% in 2020-21. Fluconazole-sensitive dose-dependant (SDD) and resistant isolates increased from 3.5% in 2018-19 to 7.7% in 2019-20 and 9.6% in 2020-21. Most resistance was in C. albicans and the majority of cases were seen in primary care. Most fluconazole non-sensitive isolates were either SDD or resistant to itraconazole (77% and 23%, respectively) and were intermediate or resistant to voriconazole (36.4% and 60%, respectively). CONCLUSION: There was a significant increase in the prevalence of NCAY and fluconazole-resistant C. albicans in complicated/RVVC cultures over these 3 years. Successful treatment of such cases can be very challenging. The exact reasons for this increase remain unclear but it follows a policy change that encouraged a clinical diagnosis and empirical treatment of vulvovaginal candidiasis, rather than fungal culture, in primary care.

Interaction of the antifungal ketoconazole and its diphenylphosphine derivatives with lipid bilayers: Insights into their antifungal action.

Ketoconazole (Ke) is an important antifungal drug, and two of its diphenylphosphinemethyl derivatives (KeP: Ph2PCH2-Ke and KeOP: Ph2P(O)CH2-Ke) have shown improved antifungal activity, namely against a yeast strain lacking ergosterol, suggesting alternative modes of action for azole compounds. In this context, the interactions of these compounds with a model of the cell membrane were investigated, using POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) large unilamellar vesicles and taking advantage of the intrinsic fluorescence of Ke, KeP and KeOP. Steady-state fluorescence spectra and anisotropy, including partition and aggregation studies, as well as fluorescence lifetime measurements, were carried out. In addition, the ability of the compounds to increase membrane permeability was assessed through carboxyfluorescein leakage. The membrane/water mole fraction partition coefficients (Kp,x): (3.31 ± 0.36) x105, (8.31 ± 1.60) x105 and (4.66 ± 0.72) x106, for Ke, KeP and KeOP, respectively, show that all three compounds have moderate to high affinity for the lipid bilayer. Moreover, KeP, and particularly KeOP interact more efficiently with POPC bilayers than Ke, which correlates well with their in vitro antifungal activity. Furthermore, although the three compounds disturb the lipid bilayer, KeOP is the quickest and most efficient one. Hence, the higher affinity and ability to permeabilize the membrane of KeOP when compared to that of KeP, despite the higher lipophilicity of the latter, points to an important role of Ph2P(O)CH2- oxygen. Overall, this work suggests that membrane interactions are important for the antifungal activity of these azoles and should be considered in the design of new therapeutic agents.

Evaluation of the drug-drug interaction between triazole antifungals and cystic fibrosis transmembrane conductance regulator modulators in a real-life cohort.

Limited data on the clinical management of drug-drug interactions between triazoles and Cystic Fibrosis transmembrane conductance regulator (CFTR) modulators are available. We retrospectively evaluated azole target attainment and dose adaptations in patients from two Dutch CF centres concomitantly receiving triazoles and CFTR modulators. In total, 21 patients with 59 triazole trough concentrations were evaluated. Subtherapeutic concentrations were frequently observed, especially for itraconazole and voriconazole. Of the investigated antifungal agents, posaconazole appears the most preferable option. Our results emphasize the importance of adequate management of this interaction and underpin the added value of therapeutic drug monitoring of triazoles in this population.

Fungal infections are serious complications in Cystic Fibrosis (CF) patients. We evaluated patients concomitantly receiving triazoles and CF transmembrane conductance regulator modulators: subtherapeutic triazole exposure was frequently observed. Posaconazole appears the preferable antifungal agent.

Advancements in nanoparticle-based therapies for multidrug-resistant candidiasis infections: a comprehensive review.

Candida auris, a rapidly emerging multidrug-resistant fungal pathogen, poses a global health threat, with cases reported in over 47 countries. Conventional detection methods struggle, and the increasing resistance ofC. auristo antifungal agents has limited treatment options. Nanoparticle-based therapies, utilizing materials like silver, carbon, zinc oxide, titanium dioxide, polymer, and gold, show promise in effectively treating cutaneous candidiasis. This review explores recent advancements in nanoparticle-based therapies, emphasizing their potential to revolutionize antifungal therapy, particularly in combatingC. aurisinfections. The discussion delves into mechanisms of action, combinations of nanomaterials, and their application against multidrug-resistant fungal pathogens, offering exciting prospects for improved clinical outcomes and reduced mortality rates. The aim is to inspire further research, ushering in a new era in the fight against multidrug-resistant fungal infections, paving the way for more effective and targeted therapeutic interventions.

Compare the efficacy of antifungal agents as primary therapy for invasive aspergillosis: a network meta-analysis.

BACKGROUND: Several antifungal agents are available for primary therapy in patients with invasive aspergillosis (IA). Although a few studies have compared the effectiveness of different antifungal agents in treating IA, there has yet to be a definitive agreement on the best choice. Herein, we perform a network meta-analysis comparing the efficacy of different antifungal agents in IA. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Clinical Trials databases to find studies (both randomized controlled trials [RCTs] and observational) that reported on treatment outcomes with antifungal agents for patients with IA. The study quality was assessed using the revised tool for risk of bias and the Newcastle Ottawa scale, respectively. We performed a network meta-analysis (NMA) to summarize the evidence on antifungal agents' efficacy (favourable response and mortality). RESULTS: We found 12 studies (2428 patients) investigating 11 antifungal agents in the primary therapy of IA. There were 5 RCTs and 7 observational studies. When treated with monotherapy, isavuconazole was associated with the best probability of favourable response (SUCRA, 77.9%; mean rank, 3.2) and the best reduction mortality against IA (SUCRA, 69.1%; mean rank, 4.1), followed by voriconazole and posaconazole. When treated with combination therapy, Liposomal amphotericin B plus caspofungin was the therapy associated with the best probability of favourable response (SUCRA, 84.1%; mean rank, 2.6) and the best reduction mortality (SUCRA, 88.2%; mean rank, 2.2) against IA. CONCLUSION: These findings suggest that isavuconazole, voriconazole, and posaconazole may be the best antifungal agents as the primary therapy for IA. Liposomal amphotericin B plus caspofungin could be an alternative option.

Management and outcome of intracranial fungal infections in children and adults in Africa: a scoping review.

INTRODUCTION: Intracranial fungal infections' (IcFIs) varying clinical manifestations lead to difficulties in diagnosis and treatment. African populations are disproportionately affected by the high burden of the disease. There is a lack of clarity as to the diagnostic and treatment modalities employed across the continent. In this review, we aim to detail the management, and outcome of IcFIs across Africa. METHODS: This scoping review was conducted using the Arksey and O'Malley framework. MEDLINE, EMBASE, Cochrane Library, African Index Medicus, and African Journals Online were searched for relevant articles from database inception to August 10th, 2021. The Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews guidelines were used to report the findings of the review. RESULTS: Of the 5,779 records identified, 131 articles were included. The mean age was 35.6 years, and the majority (56.4%) were males. The majority (n = 8,433/8,693, 97.0%) of IcFIs presented as a meningitis, the most common communicable predisposing factor of IcFIs was HIV/AIDS (n = 7,815/8,693, 89.9%), and the most common non-communicable risk factor was diabetes mellitus (n = 32/8,693, 0.4%). Cryptococcus species was the most common (n = 8,428/8,693, 97.0%) causative organism. The most commonly used diagnostic modality was cerebrospinal (CSF) cultures (n = 4,390/6,830, 64.3%) for diffuse IcFIs, and MRI imaging (n = 12/30, 40%) for focal IcFIs. The most common treatment modality was medical management with antifungals only (n = 4,481/8,693, 51.6%). The most commonly used antifungal agent in paediatric, and adult patients was amphotericin B and fluconazole dual therapy (51.5% vs 44.9%). The overall mortality rate was high (n = 3,475/7,493, 46.3%), and similar for both adult and paediatric patients (47.8% vs 42.1%). CONCLUSION: Most IcFIs occurred in immunosuppressed individuals, and despite the new diagnostic techniques, CSF culture was mostly used in Africa. Antifungals regimens used was similar between children and adults. The outcome of IcFIs in Africa was poor for both paediatric and adult patients.

Total synthesis of antifungal lipopeptide iturin A analogues and evaluation of their bioactivity against F. graminearum.

The pursuit of novel antifungal agents is imperative to tackle the threat of antifungal resistance, which poses major risks to both human health and to food security. Iturin A is a cyclic lipopeptide, produced by Bacillus sp., with pronounced antifungal properties against several pathogens. Its challenging synthesis, mainly due to the laborious synthesis of the ß-amino fatty acid present in its structure, has hindered the study of its mode of action and the development of more potent analogues. In this work, a facile synthesis of bioactive iturin A analogues containing an alkylated cysteine residue is presented. Two analogues with opposite configurations of the alkylated cysteine residue were synthesized, to evaluate the role of the stereochemistry of the newly introduced amino acid on the bioactivity. Antifungal assays, conducted against F. graminearum, showed that the novel analogues are bioactive and can be used as a synthetic model for the design of new analogues and in structure-activity relationship studies. The assays also highlight the importance of the ß-amino acid in the natural structure and the role of the stereochemistry of the amino fatty acid, as the analogue with the D configuration showed stronger antifungal properties than the one with the L configuration.

Candidemia in Adult Patients in the ICU: A Reappraisal of Susceptibility Testing and Antifungal Therapy.

OBJECTIVE: To provide updates on the epidemiology and recommendations for management of candidemia in patients with critical illness. DATA SOURCES: A literature search using the PubMed database (inception to March 2023) was conducted using the search terms "invasive candidiasis," "candidemia," "critically ill," "azoles," "echinocandin," "antifungal agents," "rapid diagnostics," "antifungal susceptibility testing," "therapeutic drug monitoring," "antifungal dosing," "persistent candidemia," and "Candida biofilm." STUDY SELECTION/DATA EXTRACTION: Clinical data were limited to those published in the English language. Ongoing trials were identified through ClinicalTrials.gov. DATA SYNTHESIS: A total of 109 articles were reviewed including 25 pharmacokinetic/pharmacodynamic studies and 30 studies including patient data, 13 of which were randomized controlled clinical trials. The remaining 54 articles included fungal surveillance data, in vitro studies, review articles, and survey data. The current 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Management of Candidiasis provides recommendations for selecting empiric and definitive antifungal therapies for candidemia, but data are limited regarding optimized dosing strategies in critically ill patients with dynamic pharmacokinetic changes or persistent candidemia complicated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Outcomes due to candidemia remain poor despite improved diagnostic platforms, antifungal susceptibility testing, and antifungal therapy selection for candidemia in critically ill patients. Earlier detection and identification of the species causing candidemia combined with recognition of patient-specific factors leading to dosing discrepancies are crucial to improving outcomes in critically ill patients with candidemia. CONCLUSIONS: Treatment of candidemia in critically ill patients must account for the incidence of non-albicans Candida species and trends in antifungal resistance as well as overcome the complex pathophysiologic changes to avoid suboptimal antifungal exposure.

Therapeutic drug monitoring of azole antifungal agents.

Deep-seated mycoses are generally opportunistic infections that are difficult to diagnose and treat. They are expected to increase with the spread of advanced medical care and aging populations, thus highlighting the need for safe, effective, and rapid drug-based treatments. Depending on a patient's age, sex, underlying diseases, and immune system status, therapeutic drug monitoring (TDM) may be important for assessing variable pharmacokinetic parameters, as well as preventing drug-drug interactions, adverse events, and breakthrough infections caused by fungal resistance. Azole antifungal agents play an important role in the prevention and treatment of deep-seated fungal infections, with each azoles having its own unique pharmacokinetic properties and specific adverse events. Therefore, it is necessary to use national and international guidelines to build evidence for the expansion of TDM indications. This review focuses on the clinical utility and future perspectives of TDM using azole antifungal agents, in the context of recent evidence in the literature.

Mucoadhesive delivery systems for oral candidiasis treatment: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis. MATERIALS AND METHODS: The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta-analysis. RESULTS: A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3-1.297; p = 0.591; I2 = 64.648) or mycological (RR = 0.95; 95CI = 0.667-1.360; p = 0.789; I2 = 73.271) efficacy. CONCLUSIONS: Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times.