Pichia kudriavzevii (formerly Candida krusei) poses a significant threat to immunocompromised patients due to its inherent resistance to various antifungal drugs. This study explored the anticandidal potential of citral, linalool, and carvacrol in combination with nystatin against P. kudriavzevii strains.Using the microdilution method following CLSI guidelines, Minimum Inhibitory Concentrations (MICs) and fungicidal concentrations (MFCs) were determined. Citral exhibited MIC values ranging from 50 to 100 µg/ml, averaging 70.24 ± 16.99 µg/ml, while carvacrol had MIC values of 50 to 100 µg/ml, averaging 86.90 ± 16.99 µg/ml. Linalool demonstrated weaker antifungal activity, with MIC values between 100 and 200 µg/ml, averaging 150 ± 38.73 µg/ml. The study assessed the synergistic effectsof these phenols with nystatin through fractional inhibitory concentration indices (FICIS). In addition, flow cytometry was employed to assess apoptosis induction in P. kudriavzevii cells.Carvacrol displayed a remarkable synergistic effect in combination with nystatin against all 21 isolates tested. Conversely, linalool showed synergy in 17 isolates, while citral exhibited synergy in only 2 isolates. These findings highlight distinct patterns of synergy between the different compounds and nystatin against P. kudriavzevii. Also, Carvacrol emerged as the most potent inducer of apoptosis across all P. kudriavzevii strains, followed by citral and linalool. This suggests that carvacrol not only possesses a stronger antifungal effect but also has a more pronounced ability to trigger programmed cell death in P. kudriavzevii. In conclusion, the study supports the potential of carvacrol, citral and linalool, as anticandidal agents, suggesting their supplementation with nystatin for treating P. kudriavzevii infections.

Cryptococcal meningitis (CM) causes significant global morbidity and mortality. Current therapeutic strategies rely on deoxycholated or liposomal forms of the polyene amphotericin B. Nystatin is also a polyene with broad-spectrum antimicrobial activity. Treatment with systemic nystatin has been limited by toxicity, which is a consistent challenge with polyene therapeutics. One mechanism to improve the toxicity is usage of a liposomal form of the active agent. Previous data from a murine candidemia model indicated that liposomal nystatin may be an effective antifungal drug formulation. Since the rabbit model of CM is a highly predictive preclinical system for evaluating antifungal therapeutics, we tested the effectiveness of two doses of daily liposomal nystatin, 3 and 8 mg/kg in the rabbit model of CM. Treatment with liposomal nystatin in this model did not reduce the fungal burden in the cerebrospinal fluid. A subsequent clinical trial also did not find activity in a human population. These data indicate that liposomal nystatin in the current form and at the tested dosages is not an effective therapy for CM. The data provide further evidence for the predictive power of the rabbit model of CM as a vital preclinical system for testing novel antifungal therapeutics for CM.

UNASSIGNED: Talquetamab is the first-in-class GPRC5DxCD3 bispecific antibody for relapsed/refractory multiple myeloma. Given limited real-world data, this study was conducted with US healthcare providers (HCPs) to understand real-world talquetamab dosing and symptom management.
UNASSIGNED: In February/March 2024, individual in-depth interviews (IDIs; n = 10) were conducted with HCPs administering talquetamab in real-world settings. A subsequent expert panel (n = 6) further discussed current practices.
UNASSIGNED: The IDIs reported a variety of settings for step-up dosing (SUD), including inpatient (n = 5), outpatient (n = 3), and hybrid models (n = 2), with a trend toward shorter SUD length to reduce healthcare resource utilization. Most HCPs used a biweekly (Q2W) schedule in SUD (n = 7) and treatment phases (n = 8). Eight participants explored reducing dose frequency to every 4 weeks (Q4W) in patients following positive disease response to treatment, considering patient convenience and relieving GPRC5D-related symptoms. Panelists recommended symptom management and prophylactic strategies, such as dexamethasone and nystatin mouthwash or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms.
UNASSIGNED: This study outlines current real-world practices for talquetamab. Findings indicate variation in the SUD care setting. The 0.8 mg/kg Q2W dosing schedule was most common, although switching to Q4W is a real-world symptom management strategy for some patients with responses to therapy. GPRC5D-related symptom management approaches are evolving; prophylactic use of dexamethasone and nystatin mouthwash or zinc and vitamin B complex may be effective strategies to alleviate oral symptoms. Further real-world evidence is needed to inform optimal dosing schedules while mitigating symptom impact.
Talquetamab is a new treatment that was approved in the United States in 2023 for a type of blood cancer called multiple myeloma. This drug is administered at one of two doses, each of which includes a defined step-up dosing schedule where patients first receive smaller amounts of the drug to help avoid serious side effects. Because talquetamab is new and associated with treatment-related symptoms not normally seen with other multiple myeloma treatments, doctors and patients need more guidance on drug administration and symptom management. In this study, we describe findings from interviews and an expert panel discussion with healthcare professionals who have experience using talquetamab. This study found that most healthcare professionals administered step-up dosing with patients staying overnight in the hospital, while other providers administered these doses during outpatient visits. Most providers administered talquetamab once every 2 weeks after utilizing the associated step-up dosing schedule. Additionally, healthcare providers described transitioning some patients, who had responded positively to treatment, to a less frequent dosing schedule of once per month to help reduce the effect of treatment-related symptoms. Participants in the expert panel described approaches for managing or preventing these symptoms, such as dexamethasone and nystatin mouthwashes or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. In summary, this study provides valuable real-world information from healthcare providers who have experience treating patients with multiple myeloma with talquetamab.

BACKGROUND: Many clinicians prescribe antifungal agents to treat canine otitis externa (OE). However, studies evaluating the antifungal effects of N-acetylcysteine (NAC) and its combinations are limited.
OBJECTIVE: The aim of this study was to evaluate the antifungal effects of NAC alone and in combination with other antifungal agents against Malassezia pachydermatis isolated from canine OE.
METHODS: M. pachydermatis samples were collected from 13 dogs with OE. The final concentration of the inoculum suspensions of M. pachydermatis was 1-5 × 106 colony forming units/mL. The concentrations of the test compounds ketoconazole (KTZ), terbinafine (TER), nystatin (NYS) and NAC were 0.02-300 µg/mL, 0.04-80 µg/mL, 0.16-40 µg/mL and 1.25-20 mg/mL, respectively. The minimum inhibitory concentration (MIC) was measured to evaluate the susceptibility of the M. pachydermatis to KTZ, TER, NYS and NAC. The checkerboard testing method and fractional inhibitory concentration index were used to evaluate the effect of NAC in combination with KTZ, TER and NYS against M. pachydermatis.
RESULTS: The MIC90 values of M. pachydermatis were 4.6875-9.375 µg/mL, 1.25 µg/mL, 5-10 µg/mL and 10 mg/mL for KTZ, TER, NYS and NAC, respectively. The synergistic effects of KTZ, TER and NYS with NAC were identified in 0/13, 2/13 and 0/13 isolates, respectively.
CONCLUSIONS: NAC had an antifungal effect against M. pachydermatis but did not exert synergistic effects when used with KTZ, TER and NYS. Thus, the use of NAC alone as a topical solution could be considered an effective treatment option for canine OE involving M. pachydermatis.

The number of copies of each chromosome, or ploidy, of an organism is a major genomic factor affecting adaptation. We set out to determine how ploidy can impact the outcome of evolution, as well as the likelihood of evolutionary rescue, using short-term experiments with yeast (Saccharomyces cerevisiae) in a high concentration of the fungicide nystatin. In similar experiments using haploid yeast, the genetic changes underlying evolutionary rescue were highly repeatable, with all rescued lines containing a single mutation in the ergosterol biosynthetic pathway. All of these beneficial mutations were recessive, which led to the expectation that diploids would find alternative genetic routes to adaptation. To test this, we repeated the experiment using both haploid and diploid strains and found that diploid populations did not evolve resistance. Although diploids are able to adapt at the same rate as haploids to a lower, not fully inhibitory, concentration of nystatin, the present study suggests that diploids are limited in their ability to adapt to an inhibitory concentration of nystatin, while haploids may undergo evolutionary rescue. These results demonstrate that ploidy can tip the balance between adaptation and extinction when organisms face an extreme environmental change.

OBJECTIVE: This study investigated the effectiveness of a drug-modified tissue conditioner in an animal model of denture stomatitis.
RESULTS: Wistar rats wore a Candida albicans-contaminated palatal device for 4 days. Next, nystatin (Nys) or chlorhexidine (Chx) were added to a tissue conditioner in their raw or β-cyclodextrin-complexed (βCD) forms at their minimum inhibitory concentrations. As controls, one group was not subjected to any procedure (NC), one group used sterile devices, one group had denture stomatitis but was not treated (DS), and another had the devices relined with the tissue conditioner without the addition of any drug (Soft). After 4 days of treatment, treatment effectiveness was assessed visually, histologically, and through CFU count, and myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats from the Soft, Nys, Nys:βCD, and Chx groups presented a significant decrease in the microbial load compared with the untreated group. Treatment groups showed lower MPO and NAG activity compared to the non-treated group.
CONCLUSIONS: The addition of antifungals to a soft tissue conditioner can be a promising approach for denture stomatitis treatment.

This study assessed the efficacy of antimicrobial photodynamic therapy (PDT) using a 650 nm diode laser combined with methylene blue (MB) as a photosensitizer to inhibit the growth of Candida albicans (C. albicans). Oral samples were collected from 75 patients diagnosed with oral thrush. C. albicans was isolated and identified using traditional methods and the VITEK 2 YST system. Samples (n = 25) were divided into five groups: Group 1 (control, n = 5) consisted of C. albicans suspensions in saline; Group 2 (n = 5) treated with nystatin; Group 3 (n = 5) exposed to a 650 nm diode laser in continuous mode at 200 mW for 300 seconds; Group 4 (n = 5) treated with 650 nm laser and MB as a photosensitizer; Group 5 (n = 5) exposed to the laser in combination with nystatin. Statistical analysis using ANOVA, Dunnett\'s t-test (P = 0.05), and LSD (P = 0.001) revealed significant differences in C. albicans counts pre- and post-treatment. Group 5 showed the most significant reduction in C. albicans, followed by Group 4, while Groups 2 and 3 showed the least variation. The findings suggest that PDT using a 650 nm diode laser with methylene blue (in continuous mode at 200 mW for 300 seconds) effectively reduced the prevalence of C. albicans.

BACKGROUND: Candida, a common oral microbiota, can cause opportunistic fungal infections. With rising Candida infections and limited effective antifungals, new treatments are needed. This study investigates carvacrol essential oil\'s effect on oral candidiasis, alone and with nystatin, compared to nystatin alone.
METHODS: In this study, oral samples were collected from dental clinic patients, especially denture users. The presence of Candida was confirmed and cultured from these samples. Candidiasis was detected by observing Candida colonies. Drug sensitivity was tested on 100 positive samples. The minimum concentration of inhibition and lethality of each isolate was evaluated using nystatin and carvacrol. The results were compared using two-way analysis of variance. Finally, the minimum inhibitory concentration (MIC) of nystatin and carvacrol was calculated individually and in combination.
RESULTS: The present study found that Candida albicans and non-albicans species were equally prevalent. Carvacrol showed significant biological activity against all Candida species, with an average MTT of 50.01%. The average MIC value of carvacrol was 24.96 µg/ml, indicating its potential to inhibit Candida growth. The mean Minimum Fungicidal Concentration (MFC) value of carvacrol was 23.48 µg/ml, suggesting its effectiveness in killing the fungi.
CONCLUSIONS: The study\'s findings reveal that the MIC of carvacrol was significantly lower than that of nystatin and the combination of nystatin and carvacrol. This suggests that carvacrol holds potential as an effective herbal remedy for candidiasis.

This study aimed to answer the question formulated according to the PICO strategy: \'Which essential oils show antimicrobial activity against biofilms formed on dental acrylic resin?\' composed by population (dental acrylic resin), intervention (application of essential oils), comparison (denture cleansers, antifungal drugs, chlorhexidine, and oral mouthwashes), and outcome (antibiofilm activity). In vitro experimental studies evaluating the activity of EOs on biofilm formed on acrylic resin were included. PRISMA guidelines were followed, and the search was performed in the PubMed, Science Direct, Embase, and Lilacs databases and in the gray literature using Google Scholar and ProQuest in December 2023. A manual search of the reference lists of the included primary studies was performed. Of the 1467 articles identified, 37 were selected for full-text reading and 12 were included. Twelve EOs were evaluated, of which 11 showed activity against Candida spp., 3 against Staphylococcus aureus, and 1 against Pseudomonas aeruginosa. The EOs of Cymbopogon citratus, Cinnamomum zeylanicum, and Cymbopogon nardus showed higher action than chlorhexidine, C. nardus higher than Listerine, C. citratus higher than nystatin, and Melaleuca alternifolia higher than fluconazole and nystatin. However, chlorhexidine was more effective than Lippia sidoides and Salvia officinalis, sodium hypochlorite was more effective than L. sidoides, nystatin was more effective than Zingiber officinale, Amphotericin B more effective than Eucalyptus globulus and M. alternifolia. In conclusion, the EOs of C. zeylanicum, C. citratus, C. nardus, and M. alternifolia showed antimicrobial activity to reduce biofilm on dental acrylic resin.

UNASSIGNED: Candida albicans is one of the most common pathogenic yeasts, responsible for causing candidiasis. The use of conventional antifungal agents for the treatment of Candida is reported to be less effective and hence alternative therapies for the treatment are needed. Essential oils of medicinal plants may serve as a strong candidate for natural products in modern therapies.
UNASSIGNED: The aim of this study was to determine the synergistic potential of essential oils extracted from leaves of Aegle marmelos (L.) Correa and a potent antifungal agent, nystatin, against three clinical isolates of C. albicans using checkerboard assay.
UNASSIGNED: The antifungal activity of the essential oils of A. marmelos was screened against test cultures by disc diffusion technique. Antibiograms of the test organisms were developed. To determine the minimum fungicidal concentration of the essential oil and nystatin, the broth microdilution method was employed, and a checkerboard assay was used to investigate the synergistic potential of the essential oil and nystatin against the clinical isolates under study. The data were expressed as mean ± standard deviation.
UNASSIGNED: The Σ fractional inhibitory concentration values were calculated as 0.12, 0.37, and 0.28 for three different strains of C. albicans used, respectively, which was <0.5, therefore, the synergy was demonstrated between essential oils and nystatin against the test cultures.
UNASSIGNED: Combinatorial therapy of the essential oils extracted from the leaves of A. marmelos and nystatin may be considered a line of treatment for candidal infections.