Treatment Of Candidiasis Research Articles

Dual-action of clotrimazole loaded - nanosponges vaginal gel for spermicidal action and treatment of vaginal candidiasis: Optimization, in-vitro, ex-vivo, and in-vivo experiments.

Clotrimazole (CLO) is a strong antifungal drug approved to treat vaginal candidiasis (VC). Nanosponges (NSs) were developed to maintain providing CLO in a steady pattern with amplified accumulation in the vaginal mucosa. The quasi-emulsion solvent diffusion method was utilized to prepare NSs. The optimized NSs selected by Design Expert® exhibited a production yield percent (PY%) of 60.10±0.39%, encapsulation efficiency percent (EE%) of 91.21±0.59%, particle size (PS) 275.50±0.97nm, polydispersity index (PDI) 0.425±0.01, and zeta potential (ZP) of -27.40±0.25mV. The morphological results confirmed a spongy, porous structure. Fourier Transform Infrared Spectroscopy ensured the drug encapsulation. Differential scanning calorimetric studies showed no interaction between the excipients and CLO. The prepared NSs-loaded gel of optimized CLO-NSs was evaluated, the mucoadhesive strength (6065.85±52.03 dyne/cm2) with spermicidal activity of (0% sperm motility/60s). The ex-vivo deposition depicted significantly increased vaginal retention of CLO by 2.44-fold compared to Candistan® 2% vaginal cream (the market product). Finally, the in-vivo study on rats demonstrated thesuperior efficacy of CLO-NSs gel relative to Candestan®, with significantly reduced inflammatory biomarkers and minimal histopathological alterations in the treatment of vaginal candidiasis with a high safety profile.

P-1096. Activity of Ibrexafungerp and Comparator Antifungals Tested against Candida and Aspergillus Isolates Collected from Invasive Infections in a Global Surveillance Program in 2023

Abstract Background Ibrexafungerp (IBX) is a novel triterpenoid antifungal agent that was approved by the U.S. FDA for the treatment of vulvovaginal candidiasis (VVC) in 2021. Further studies are ongoing to assess the efficacy of IBX for the treatment of invasive candidiasis (IC) and other refractory fungal infections, including aspergillosis. CLSI, EUCAST, or FDA clinical breakpoints or epidemiological cutoff values are not yet defined for IBX against fungi. We evaluated the activity of IBX and comparator agents against clinical isolates from IC and invasive aspergillosis infections collected from a global surveillance program in 2023. MIC50/90 (mg/L) for ibrexafungerp (IBX) and comparator agents against 5 most common Candida spp., C. auris, and 3 most common Aspergillus spp. in 2023 SENTRY Antifungal Surveillance Program Methods A total of 1120 Candida spp. and 204 Aspergillus spp. isolates consecutively collected as part of the SENTRY Program were evaluated. Isolates were recovered from 11 medical centers in North America, 18 in Europe, 7 in Asia-Pacific, and 5 in Latin America. Identification was performed by MALDI-TOF MS and/or sequencing and susceptibility testing was performed using the CLSI broth microdilution method for IBX, anidulafungin (AND), micafungin (MFG), fluconazole (FLC), itraconazole (ITC), and voriconazole (VRC). Results Table 1 displays MIC50/90 results for the 5 most common Candida spp., C. auris, and the 3 most common Aspergillus spp. The IBX MIC50/90 results were low against all organisms including organisms of critical concern like C. auris. Among Candida species, IBX had similar or higher MIC50/90 to AND except for C. parapsilosis where IBX MIC50/90 values were 4- to 8-fold lower. MFG was more potent (4- to 16-fold) against most Candida spp. except for C. parapsilosis where IBX had 2-to 4- fold lower MIC50/90 and C. auris where IBX was similar to MFG. Notably, the highest MIC result observed for IBX against C. auris was 1 mg/L. MIC50/90 values for IBX were also 8- to > 256-fold lower than azoles against Aspergillus spp. but higher (2- to ≥ 16-fold) than MFG or AND. Conclusion IBX has good activity against the predominant Candida and Aspergillus species from a worldwide contemporary collection. This agent may represent an oral option for the management of difficult-to-treat invasive fungal pathogens such as C. glabrata, C. auris, and Aspergillus spp. from diverse infection sources in addition to its current indication for VVC. Disclosures Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support Sharon Min, MS, GSK: Employee

P-1034. Week One Outcomes of Rezafungin vs Caspofungin Treatment for Candidemia and Invasive Candidiasis (CIC): Pooled Analysis of Two Randomized Trials Exploring Optimal Echinocandin Duration

Abstract Background The Phase 2 STRIVE and Phase 3 ReSTORE trials demonstrated the efficacy and safety of rezafungin for treating CIC. With data suggesting early treatment benefit for rezafungin, possibly due to its front-loaded dosing, this pooled analysis of the data assessed the outcomes of the first week of treatment in relation to later timepoints exploring the optimal duration of echinocandin therapy.Figure .Day 7 outcomes: (A) % (95% CI) difference in ACM rate (rezafungin – caspofungin), (B) % (95% CI) difference in mycological response rate (rezafungin – caspofungin), and (C) median (IQR) TTNBC in pts with a positive blood culture before randomization (mITT population). Methods STRIVE/ReSTORE were randomized, double-blind trials. Pts ≥18 yrs with CIC received once-a-week IV rezafungin (400 mg on Week 1, then 200 mg weekly) or once-a-day IV caspofungin (70 mg loading, then 50 mg daily) for 28 days. Efficacy was evaluated in the pooled modified intent-to-treat (mITT) population (rezafungin n=139, caspofungin n=132). Endpoints were all-cause mortality (ACM), mycological response, and time to first negative blood culture (TTNBC; in pts with a positive blood culture before randomization) at Day (D) 7, D14, and D30. Treatment-emergent adverse events (TEAEs) were assessed up to D7 in the pooled safety population (rezafungin n=151, caspofungin n=166).Table.Day 7 safety (safety population) Results Safety of rezafungin in Week 1 was comparable to its overall safety profile and the safety of caspofungin (Table). Most frequent TEAEs in Week 1 were hypokalemia, diarrhea, and anemia. ACM was similar between the two groups at D7 (% difference [95% CI] [rezafungin – caspofungin], 2.1 [-5.0, 9.2]; Figure A), D14 (1.7 [-6.4, 9.7]), and D30 (-2.3 [-12.0, 7.4]). Mycological response was also comparable between the groups at D7 (% [95% CI] difference in eradication rate, 7.6 [-3.5, 18.6]; Figure B), D14 (5.3 [-5.7, 16.2]), and D30 (7.7 [-3.6, 19.0]). TTNBC was shorter for rezafungin vs caspofungin (median, 22.3 vs 24.3 h; p< 0.05). D7 subanalyses were limited by small numbers (Figure C) but showed that TTNBC was shorter for rezafungin vs caspofungin in pts with candidemia (median, 22.3 vs 23.4 h; p=0.0182). Conclusion Rezafungin demonstrated good safety and efficacy comparable to that for caspofungin in the first week of treatment. Rezafungin resulted in shorter TTNBC compared to caspofungin. These data provide the foundation for future investigation of the optimal duration of echinocandin therapy for invasive candidiasis. Disclosures Luis Ostrosky-Zeichner, MD, FACP, FIDSA, FSHEA, FECMM, CMQ, Cidara: Advisor/Consultant|Enanta: Advisor/Consultant|F2G: Advisor/Consultant|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Octapharma: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pulmocide: Grant/Research Support|Scynexis: Grant/Research Support|Viracor: Advisor/Consultant Mark A. Redell, PharmD, Johnson & Johnson: Stocks/Bonds (Public Company)|Melinta Therapeutics: Full-time employee|Melinta Therapeutics: Stocks/Bonds (Private Company) Jalal A. Aram, M.D., Melinta Theraputics: Employee

Potential risk of cross-resistance to voriconazole in HIV/AIDS patients with Talaromyces marneffei infection and the mechanisms of the cross-resistance.

The use of fluconazole for long-term oral candidiasis treatment in HIV/AIDS patients can potentially affect the clearance rate and antifungal efficacy of voriconazole against Talaromyces marneffei infection. We isolated two T. marneffei strains that were both resistant to fluconazole and voriconazole. To investigate the mechanism underlying the induction of the cross-resistance in T. marneffei. Fluconazole-resistant strains were induced in vitro. The target enzyme 14-α sterol demethylase Cyp51B was sequenced, and drug efflux pump expression was determined by RT-qPCR in all strains. The sensitivity of fluconazole-induced resistant strains to fluconazole was greater than 128 mg/L, and this resistance was stably inherited after fluconazole pressure was removed. MICs of voriconazole for resistant strains were 4∼16 times greater than FRR (0.25-1 versus 0.06 mg/L). Two mutation hotspots in Cyp51B were detected: G441D and G441V. The AtrF, Mdr1 and Pmfcz genes were significantly overexpressed in the vast majority of the fluconazole-resistant strains (P < 0.05). The growth of T. marneffei in the presence of fluconazole could induce voriconazole resistance in vitro. The main cause of this cross-resistance in T. marneffei appears to be related to a mutation in Cyp51B at G441 and overexpression of the efflux pumps AtrF, Mdr1 and Pmfcz.

Comparing the effects of Mycozin and Clotrimazole 1% creams on vaginal candidiasis: a triple-blinded randomized controlled trial

Clotrimazole 1% and Mycozin vaginal cream have been reported to be effective in relieving the symptoms of vulvovaginitis caused by Candida. The resistance to azole compounds, and the side effects of chemical drugs have been reported following azole therapy. It was hypothesized that Mycozin is at least as effective as Clotrimazole in treating vaginal candidiasis. This equivalent, triple-blinded, randomized clinical trial was conducted on 126 patients who complained of vaginal itching referred to Al-Zahra Teaching Hospital, Tabriz, Iran between September 2023 and May 2024. Participants were divided into two groups, i.e., Mycozin (n = 64) and Clotrimazole 1% (n = 62), using the block randomization method. The patient's complaints, clinical signs, the pH and culture of the secretions was recorded before and after treatment. The patient's improvement, level of satisfaction, and side effects were recorded. The data were analyzed using Pearson chi-square test, ANCOVA, and Mann–Whitney U test. There was no statistically significant difference between the two groups regarding the mean pH (Adjusted mean difference: 0.01; 95% Confidence Interval (CI): −0.20 to 0.21, P = 0.965), and microscopic evaluation (Odds Ratio (OR): 0.61; 95% CI; 0.28 to 1.36, P = 0.230). After the treatment the frequency of itching in the Clotrimazole group (N = 13; 22.0%) was lower than that of the Mycozin group (N = 26; 43.3%) (OR: 0.37; 95% CI: 0.17 to 0.82; P = 0.013). There was no statistically significant difference in other symptoms and signs before and after the treatment (P > 0.05). Also, there was no statistically significant difference between the two groups in the level of satisfaction (P = 0.056) and patient improvement (P = 0.074). The side effects of treatment with Mycozin and Clotrimazole were observed in eleven and five patients, respectively. Considering the efficacy of Mycozin vaginal cream in eliminating most of the symptoms and signs associated with vaginal candidiasis and its positive effect in negating the results of culture, it can be used as a suitable alternative in the treatment of vaginal candidiasis in patients interested in herbal medicines and resistant to azole compounds.Trial registration: Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N77. Date of registration: 20/05/2023; URL: https://irct.behdasht.gov.ir/user/trial/68718/view; Date of first registration: 31/05/2023.

In vitro photodynamic therapy of Candida albicans, the cause of vulvovaginal candidiasis, is enhanced by Bacillus and Enterococcus probiotics.

Candida albicans is the primary cause of vulvovaginal candidiasis, a worldwide health concern for women. The use of supplemental methods, such as antimicrobial photodynamic therapy (aPDT) and probiotics, was promoted by the ineffectiveness of the existing antifungal drugs. This study examines the combined effects of probiotics (Bacillus and Enterococcus isolated from the fermented pickles) and PDT (using red laser (655 nm, 18 J/cm2) as a light source and methylene blue dye (30 mg/mL) as a photosensitizer) on the in vitro virulence activity of C. albicans including growth, biofilm formation, antifungal resistance, biofilm elimination, and biofilm dispersion. The probiotic strains demonstrated a higher resistance to PDT compared to the fungal cell. Bacillus and Enterococcus enhanced the antifungal effects of PDT on planktonic Candida cells in both pre-PDT and post-PDT interactions. The inhibition of biofilm formation by PDT was improved upon interaction with Bacillus (70%) and Enterococcus (58%). The eradication of Candida biofilm using PDT was increased after a combination with Bacillus (67%) and Enterococcus (46%). The nystatin resistance of the fungal biofilm following PDT treatment was decreased from (µg/ml) 25 to 6.25 due to the interaction with both probiotic strains. Fungal cell dispersion from the biofilm after PDT treatment diminished by 18% and 25% in the presence of Bacillus and Enterococcus strains. Galleria mellonella mortality was significantly changed following the PDT of the fungi/probiotic-injected larvae. This synergistic activity suggests the use of probiotics/PDT as a supplemental treatment for vulvovaginal candidiasis.

Comparative efficacy of antifungal drugs for the treatment of oral candidiasis in HIV-positive patients: A Bayesian network meta-analysis

Comparative efficacy of antifungal drugs for the treatment of oral candidiasis in HIV-positive patients: A Bayesian network meta-analysis

Antifungal treatment for oral candidiasis

Introduction: the use of antifungal and/or fungistatic drugs of the azole or echinocandin type has decreased its effectiveness due to the mutagenic capacity of the Candida species.Objective: to characterize aspects related to the antifungal treatment and resistance of oral candidiasis.Method: a bibliographic search of articles published during the last 10 years will be carried out in the PubMed, Scielo and Google Scholar databases; in the English and Spanish languages. The selection of the works was carried out from the title and the abstract in a first instance, by a single operator.Results: adding the articles searched with the key words, 5,501 articles were obtained in the three different databases. Based on the title of each article, 5,400 studies were excluded for not being in accordance with the inclusion criteria. 51 articles were eliminated after reading the abstract. In the complete reading of 50 articles, 30 works were chosen.Conclusions: the search for an ideal antifungal agent remains a challenge as resistance to these treatments has developed, such that no antifungal agent currently meets all the requirements of an ideal drug for the treatment of Candida.

Hybrid Nanoparticles Dual‐Loaded With Curcumin and Benzydamine Hydrochloride for the Treatment of Vulvovaginal Candidiasis: From Development to Biological Application In Vitro and In Vivo (Adv. Therap. 1/2025)

Hybrid Nanoparticles Dual‐Loaded With Curcumin and Benzydamine Hydrochloride for the Treatment of Vulvovaginal Candidiasis: From Development to Biological Application In Vitro and In Vivo (Adv. Therap. 1/2025)

Riboflavin- and Hypericin-Mediated Antimicrobial Photodynamic Therapy as Alternative Treatments for Oral Candidiasis: A Systematic Review.

Background: Oral candidiasis, predominantly caused by Candida albicans, presents significant challenges in treatment due to increasing antifungal resistance and biofilm formation. Antimicrobial photodynamic therapy (aPDT) using natural photosensitizers like riboflavin and hypericin offers a potential alternative to conventional antifungal therapies. Material and Methods: A systematic review was conducted to evaluate the efficacy of riboflavin- and hypericin-mediated aPDT in reducing Candida infections. The PRISMA framework guided the selection and analysis of 16 eligible studies published between 2014 and 2024. Data on light parameters, photosensitizer concentrations, and outcomes were extracted to assess antifungal effects. Results: Both riboflavin- and hypericin-mediated aPDT demonstrated significant antifungal activity, achieving substantial reductions in Candida biofilm and planktonic cell viability. Riboflavin activated by blue light and hypericin activated by yellow or orange light effectively targeted fluconazole-resistant Candida strains with minimal cytotoxicity to host tissues. However, complete biofilm eradication remained challenging, and variations in protocols highlighted the need for standardization. Conclusions: Riboflavin- and hypericin-mediated aPDT present promising, biocompatible alternatives for managing antifungal resistance in Candida infections. Further clinical trials and standardized protocols are essential to optimize outcomes and confirm efficacy in broader clinical settings.

New Perspectives on Antimicrobial Agents: Rezafungin.

Candidemia and invasive candidiasis persist as significant causes of morbidity and mortality. As fluconazole resistance rates rise, alternative means of treatment are necessary, either via mold-active azoles or extended durations of echinocandins. These come with the potential for undesirable side effects for triazoles or choosing between prolonged hospitalization or outpatient parenteral antimicrobial therapy in the case of echinocandins. Rezafungin offers an opportunity to manage extended treatment durations with shorter hospital stays and no extended parenteral access. Herein, we review the most recent published data pertaining to rezafungin including anti-fungal activity, pharmacokinetics, and clinical data relating to the treatment of invasive candidiasis. Given its prolonged half-life allowing for once-weekly dosing, rezafungin has the potential as an anti-fungal prophylactic agent in high-risk patients, and studies to examine this potential role are ongoing.

Perspectives on the Use of Echinocandins in the Neonatal Intensive Care Unit.

The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive Candida infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been demonstrated to enhance the prognosis. Factors that should be considered in the choice of an antifungal agent include the causative Candida strain, the presence and location of deep tissue infection, any previous use of antifungal prophylaxis, and the presence of implanted devices. Amphotericin B and fluconazole, the first-line drugs for neonatal candidiasis, are not always suitable due to several limitations in terms of efficacy and adverse effects. Therefore, alternative antifungals have been studied and used in neonates when conventional antifungals are ineffective or contraindicated. This narrative review aims to provide an overview of the current literature regarding the use of echinocandins in the neonatal population. The three echinocandins, micafungin, caspofungin, and anidulafungin, share characteristics that make them useful for the treatment of neonatal candidiasis, including activity against a wide range of Candida strains and Candida biofilms and a favorable safety profile.

Development of amphotericin B inclusion complex formulation in dissolvable microarray patches for intravaginal delivery.

Amphotericin B (AMB) is a drug used to treat vulvovaginal candidiasis (VVC), which is a fungal infection affecting the vagina and vulva. Nevertheless, the substance's limited capacity to dissolve in water leads to poor absorption when taken orally, hence diminishing its therapeutic efficacy. In order to address this limitation, β-cyclodextrin (βCD) was used to create AMB in the form of an inclusion complex. This study aims to enhance the solubility and bioavailability of AMB by formulating it into an inclusion complex with βCD. Subsequently, we developed dissolvable microarray patches (DMP) as a novel drug delivery system, optimizing the formulation for improved retention, penetration, and controlled release of AMB. The stability of the AMB-βCD inclusion complx (IC) structure has been confirmed by employing molecular docking studies. The formulation of DMP involved the incorporation of IC with polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). The mechanical strength, ability to be inserted, and propensity to irritate Amphotericin B-Inclusion Complex-Dissolvable Microarray Patches (IC-DMP) were evaluated by laboratory experiments utilizing the porcine vaginal mucosal layer. Further investigations, such as Differential Scanning Calorimetry (DSC), were performed to assess the physicochemical characteristics of the IC. The solubility of the pure medication was greatly enhanced up to fourfold by the inclusion complex. The assessment of IC-DMP exhibited exceptional mechanical robustness and insertion abilities, with no indications of discomfort. Among the formulas tested in ex vivo vaginal kinetic experiments, Formula F3 had the most effective retention in the porcine vaginal mucosal layer. It had an AUC value of 208.02 ± 0.33h.µg/cm3 and the highest Cmax value of 20.05 ± 0.06µg/cm3. Therefore, Formula F3 was the most efficient formula in terms of vaginal drug delivery. The integration of IC into the DMP system significantly enhances the solubility and bioavailability of AMB, facilitating its absorption in the circulatory system when applied intravaginally for vulvovaginal candidiasis treatment. These promising initial findings support further clinical evaluation of this novel drug delivery system.

Bioactive Potential of Chitosan-Oleic Acid Nanoparticles Loaded with Lemon Peel Essential Oil for Topical Treatment of Vulvovaginal Candidiasis.

The rising incidence of vulvovaginal candidiasis (VVC) has been leading to the development of alternative antifungal therapies. This study aimed to develop a topical chitosan-oleic acid nanoparticle (CH-OA-NP) cream loaded with lemon peel essential oil (LPEO) for VVC treatment. The characterization of the optimal nanoparticle formulation (F4: 10 g/L CH, 2:1 OA/LPEO ratio) showed high encapsulation efficiency, stability, and controlled release. Moreover, it was characterized regarding its particle size, polydispersity index, zeta potential, and chemical/morphological profile. LPEO-related compounds (e.g., eriodictyol) were identified through LC-ESI-QqTOF-HRMS in the cream matrix, suggesting the preservation of LPEO potential bioactivities after formulation. In silico docking of 12 LPEO metabolites revealed that compounds such as citronellic acid exerted inhibitory effects against several inflammation-associated enzymes (e.g., 14-α-Demethylase). In vitro antimicrobial tests demonstrated remarkable activity against Candida albicans, Gram-negative (e.g., Escherichia coli), and Gram-positive (e.g., Staphylococcus aureus) bacteria. In vivo studies in a rat model of VVC revealed significant antifungal, anti-inflammatory, and immunomodulatory effects of the LPEO-CH-OA-NP cream (5% and 10%), leading to reduced MDA, MPO, and IL-1β levels and increased GSH activity. This novel formulation potentially offers a promising alternative therapy for VVC, addressing the current antifungal therapies' limitations, counteracting drug resistance.

CO145 Comparative Effectiveness of Echinocandins in the Treatment of Invasive Candidiasis: A Systematic Review and Network Meta-Analysis

CO145 Comparative Effectiveness of Echinocandins in the Treatment of Invasive Candidiasis: A Systematic Review and Network Meta-Analysis

A Comparative Review of Eugenol and Citral Anticandidal Mechanisms: Partners in Crimes Against Fungi.

Candida albicans is an emerging multidrug-resistant opportunistic pathogen that causes candidiasis, superficial infections on the mucosa, nails or skin, and life-threatening candidemia in deep tissue when disseminated through the bloodstream. Recently, there has been a sharp rise in resistant strains, posing a considerable clinical challenge for the treatment of candidiasis. There has been a resurged interest in the pharmacological properties of essential oils and their active components, for example, monoterpenes with alcohol (-OH) and aldehyde (-CHO) groups. Eugenol and citral have shown promising in vitro and in vivo activity against Candida species. Although there is substantial research on the efficacy of these essential oil components against C. albicans, a detailed knowledge of their mycological mechanisms is lacking. To explore the broad-spectrum effects of EOs, it is more meaningful and rational to study the whole essential oil, along with some of its major components. This review provides a comprehensive overview of eugenol and citral anticandidal and antivirulence activity, alone and together, along with the associated mechanisms and limitations of our current knowledge.

Kushen Gel combined with antifungal drugs for the treatment of vulvovaginal candidiasis: A systematic review and meta-analysis of randomized controlled trials

Ethnopharmacological relevanceVulvovaginal candidiasis (VVC) represents the most prevalent form of candidal infections, imposing a significant societal burden. Kushen gel, a chinese patent medicine, has demonstrated favorable outcomes in the treatment of VVC. In clinical practice, Kushen gel is often used in conjunction with antifungal drugs. However, the clinical evidence supporting the combined use of Kushen gel with antifungal drugs for the treatment of VVC is currently limited. Aim of the studyThis study aimed to evaluate the effectiveness and safety of Kushen gel combined with antifungal drugs in the treatment of vulvovaginal candidiasis (VVC). Materials and methodsDatabases namely CNKI, Wanfang Database, VIP Database, CBM, PubMed, Cochrane Library, and Embase were searched from their inception to January 2024. Randomized controlled trials (RCTs) applying Kushen gel combined with antifungal drugs for the treatment of VVC were included. Methodological quality assessment was performed using the Cochrane risk of bias assessment tool (RoB 1.0). A Meta-analysis was performed using RevMan 5.4 software. The primary outcomes were total efficacy rate, recurrence rate, secondary outcomes included adverse events and time to clinical symptom resolution. ResultsA Meta-analysis of 42 RCTs, encompassing a total of 4259 VVC patients was conducted. The results indicated that compared to antifungal drugs alone, Kushen gel combined with antifungal drugs increased the effectiveness (RR = 1.20, 95%CI [1.17, 1.23], P < 0.00001) and reduced the recurrence rate (RR = 0.21, 95%CI [0.13, 0.34], P < 0.00001), with no significant difference in safety (RR = 0.56, 95%CI [0.30, 1.03], P = 0.11). ConclusionsBased on the available results, it appears that the combination of Kushen gel with antifungal drugs may increase the effectiveness and reduce the recurrence rate. However, due to the poor methodological quality of the included studies, more high-quality evidence from large-sample and well-designed research is needed in the future.

Synergistic potential of Bauhinia holophylla leaf extracts with conventional antifungals in the inhibition of Candida albicans: A new approach for the treatment of oral candidiasis

ObjectiveThis study investigated the combination of Bauhinia holophylla (Bong.) Steud. leaf extracts with conventional antifungal agents, highlighting the extracts' potential as adjuvants in treating oral candidiasis. DesignEthanolic and aqueous extracts of B. holophylla leaves were analyzed using ultra-high-performance liquid chromatography with a diode array detector (UHPLC-DAD) to assess their chemical composition. Their Minimum Inhibitory Concentration (MIC) against standard strains of Candida albicans and isolates from oral mucosa was determined. Additionally, the potential synergistic effects with chlorhexidine gluconate, nystatin, and fluconazole were investigated, along with their impact on inhibiting and disrupting biofilm formation, germ tube formation of C. albicans, and cytotoxicity in human erythrocytes. ResultsProtocatechuic acid, epicatechin, and rutin were identified in both extracts. They exhibited fungistatic activity with a median minimum inhibitory concentration (MIC50) of 15.62 µg/mL for the ethanolic extract (EEB) and 62.50 µg/mL for the aqueous extract (AEB) against C. albicans. In growth kinetics, both extracts reduced the viable cell count of C. albicans by 2 logs after 24 h compared to the positive control. The extracts reduced germ tube formation by 81.6 % for EEB and 86.3 % for AEB. The synergistic combination with fluconazole and nystatin resulted in a 50 % reduction in the concentration required to inhibit C. albicans growth. No hemolytic activity was detected in human erythrocytes at the tested concentrations. ConclusionBoth ethanolic and aqueous extracts show promising potential as adjuvants in managing oral candidiasis. Notably, the aqueous extract is advantageous due to its non-toxic solvent, cost-effectiveness, and ease of preparation.

Pullulan nanoparticles inhibit the pathogenicity of Candida albicans by regulating hypha-related gene expression.

The pathogenic process of Candida albicans, the primary causative species of candidiasis, involves hyphal growth, biofilm formation, and secretion of virulence factors. Of these factors, the biofilm, created by the secretion of extracellular matrix from adherent cells, shields cells from external threats, enabling them to withstand high concentrations of antifungal agents. Therefore, suppressing biofilm formation is a crucial aspect of combating candidiasis. This study developed phthalic pullulan nanoparticles (PPNPs) as a novel material for inhibiting C. albicans' pathogenicity. PPNPs were internalized within Candida cells and reduced pathogenicity at the gene expression level, resulting in reduced in vitro biofilm formation, adhesion to human cells, and mortality of infected Caenorhabditis elegans. Moreover, PPNPs exhibited these effects without toxicity to human cells and host animals. These findings not only indicate that PPNPs can be employed to hinder in vitro biofilm formation but also suggest their potential as a novel treatment for candidiasis.

The distinctive pharmacokinetic profile of rezafungin, a long-acting echinocandin developed in the era of modern pharmacometrics.

Echinocandin drugs are the current first-line therapy for fungal infections caused by Candida spp. Most patients require once-daily intravenous (IV) administration in a hospital or outpatient setting for treatment, which may negatively impact their quality of life and stress healthcare resources. Similar to other echinocandins, the novel FDA-, EMA-, and Medical and Healthcare Products Regulatory Agency-approved echinocandin, rezafungin (CD101), exhibited strong antifungal activity against several fungal pathogens and a low drug-drug interaction liability, which are important for medically complex patients. A pharmacometric-based approach has been adopted throughout the development of rezafungin, which contrasts with older echinocandins where dosing regimens were largely derived empirically, and only recently based on pharmacometric guidance. This state-of-the-art approach used model-based simulations incorporating pre-clinical and clinical data as it became available to optimize the dosing regimen for rezafungin. The enhanced stability of the molecular structure and the safety profile of rezafungin allow for the administration of once-weekly IV doses, compared to the daily dosing requirement for other echinocandin drugs, with this distinctive pharmacokinetic profile of rezafungin resulting in a front-loaded dosing regimen with high exposures early in therapy for enhanced fungal killing. The long shelf-life of rezafungin makes this echinocandin more flexible in terms of storage and manufacturing. Demonstrated across clinical development, rezafungin may provide patients with next-generation first-line antifungal treatment for the treatment of candidaemia and invasive candidiasis.