Comparative characteristics of different methods of treatment of microsporia

Microsporia is the most common disease of fungal etiology, most often caused by the pathogen Microsporum canis. Treatment of this disease requires a comprehensive approach, because the disease is dangerous to humans. Therefore, in the treatment of microspores, it is important not only to carry out therapeutic measures, but also to prevent the spread of the pathogen of the fungus in the environment and increase the immune status of the organism in the fight against infection. The main source of infection is cats. In order to determine the effectiveness of treatment of microsporia by various methods, studied of the blood and skin of guinea pigs infected with the pathogen M. canis. Sick animals were divided into three groups. The first group was treated with the systemic antifungal itraconazole and topical treatment with a solution of clotrimazole. Treatment of the second group was performed with a topical antifungal agent (1% solution of clotrimazole) with vaccination with the antifungal vaccine “Vakderm”. For the third group, the developed drugs were used – antifungal agent “Micromar” and immunostimulant “Biogluk”. During treatment, hematological and immunological blood researches and histological skin examinations were performed. During treatment with antifungal drugs (itraconazole and clotrimazole) the number of leukocytes decreases from 11.13 ± 0.72 to 7.13 ± 0.22, rod-shaped neutrophils from 15.76 ± 1.29 to 5.50 ± 0.76, and segmental increases from 12.17 ± 1.47 to 24.17 ± 2.27, decreases ESR from 5.67 ± 0.67 to 2.33 ± 0.42, which occurs when inhibiting the inflammatory response of the organism to infection. Thrombocytopenia (from 231.17 ± 7.60 to 184.33 ± 7.65) and eosinophilia (from 2.70 ± 0.73 to 7.33 ± 1.33) are also noted. There is a slight increase in T-helpers and a decrease in T-suppressors. Histologically, the infiltration of the dermis by histiocytes and eosinophils under skin persists. In the treatment of microsporia by treatment with 1 % solution of clotrimazole and vaccination with the vaccine “Vakderm” the results of studies showed that the number of leukocytes decreases from 11.13 ± 0.72 to 5.35 ± 0.31 (P < 0.01), rod-shaped neutrophils from 15.76 ± 1.29 to 7.67 ± 0.56, and segmental increases from 12.17 ± 1.47 to 22.17 ± 0.91 (P < 0.001), decreases). The number of T-helpers is increasing. The histological picture on day 7 is characterized by hyperkeratosis, and on day 14 the hyperemia of the basal layer of the epidermis persists. When using the antifungal drug “Micromar” and immunostimulant “Biogluk” the results of studies showed that the number of leukocytes decreases from 11.13 ± 0.72 to 6.95 ± 0.10, rod-shaped neutrophils from 15.76 ± 1.29 to 6.17 ± 0.65, and segmental increases from 12.17 ± 1.47 to 22.00 ± 0.86, decreases ESR from 5.67 ± 0.67 to 2.17 ± 0.31. Increases the number of T-helpers and the number of natural killers and T-suppressors is gradually decreasing. Histological changes are presented in the form of dilation of blood vessels and visualization of single erythrocytes in the dermis on day 14 of treatment.

Antifungal Susceptibility of Aspergillus flavus, Aspergillus ochraceus, and Fusarium graminearum to Ganoderma lucidum Extract

Background: Ganoderma lucidum is a well-known fungus that has been widely used in traditional medicine around the world, especially in East Asia, due to its various health promotion properties. Recently, researchers have drawn attention to the biologically active compounds found in this fungus, and this fungus has become very popular due to its pharmaceutical properties. Objectives: The aim of this study was to investigate the antifungal properties of the Iranian strain of G. lucidum as a natural antifungal agent against harmful filamentous fungi common in the food industry. Methods: Three filamentous fungi, including Aspergillus flavus, Aspergillus ochraceus, and Fusarium graminearum, were used in this study for the antifungal evaluation of ethanolic, hydroalcoholic, and two aqueous extracts of G. lucidum with different concentrations by the broth microdilution method. Results: The results showed that only the ethanolic and hydroalcoholic extracts completely inhibited the growth of A. flavus at 2 and 3.5 mg/mL, respectively. Also, no antifungal activity was observed for the aqueous extract for all the three studied fungi. In addition, A. flavus was found to be more sensitive to G. lucidum extracts compared to the two other studied fungi. Conclusions: The ethanolic extract of G. lucidum was effective on A. flavus and can be used as a natural antifungal agent to prevent the growth of this harmful filamentous fungus.

Trichoderma reesei Contains a Biosynthetic Gene Cluster That Encodes the Antifungal Agent Ilicicolin H

The trili biosynthetic gene cluster (BGC) from the well-studied organism Trichoderma reesei was studied by heterologous expression in the fungal host Aspergillus oryzae. Coexpression of triliA and triliB produces two new acyl tetramic acids. Addition of the ring-expanding cytochrome P450 encoded by triliC then yields a known pyridone intermediate to ilicicolin H and a new chain-truncated shunt metabolite. Finally, addition of the intramolecular Diels-Alderase encoded by triliD affords a mixture of 8-epi ilicicolin H and ilicicolin H itself, showing that the T. reesei trili BGC encodes biosynthesis of this potent antifungal agent. Unexpected A. oryzae shunt pathways are responsible for the production of the new compounds, emphasising the role of fungal hosts in catalysing diversification reactions.

Reversible infertility in male dog following prolonged treatment of Malassezia dermatitis with ketoconazole

Background Ketoconazole, an antifungal agent, adversely affects spermatogenesis in rodents, but knowledge on adverse effects of prolonged administration of ketoconazole on the fertility of male dogs is lacking. A case of reversible infertility with azoospermia in a male American Staffordshire terrier treated with ketoconazole is reported here. Case presentation A seven-year old male American Staffordshire terrier treated for 3 months with ketoconazole for a persistent Malassezia dermatitis displayed reduced libido and mating of 3 bitches had been unsuccessful. The dog was presented at the clinic 40 days after the treatment had been stopped. At first presentation, low libido and complete absence of sperm in the ejaculate (azoospermia) associated with low testosterone level were found. Repeated examinations revealed that sperm quality and testosterone level had restored 100 days after ketoconazole had been withdrawn. Thereafter, the dog successfully mated 2 bitches. Conclusion The treatment with ketoconazole for 3 months may have led to reversible infertility characterized by azoospermia. Therefore, owners of stud dogs should be informed of this risk prior to initiating such treatment and in case of infertility, previous treatment with ketoconazole should be considered as a possible cause.

Comparative Evaluation of Effectiveness of Denture Adhesive after Incorporating Antifungal Agent – An In-vitro Study

Aims: The aim of current study is to evaluate adhesive force and qualitative mycological culture analysis of Denture adhesive (DA) after incorporating antifungal agent in various concentrations. Study Design: Experimental study. Place and Duration of Study: The current study was conducted at the Department of Prosthodontics, Mansarovar Dental College and Hospital, Bhopal (M. P.) from September 2017 to October 2018. Methodology: A total of 80 specimens were prepared with heat cured acrylic resin, out of which 40 were used for qualitative anti-microbiological test, and 40 were used for Adhesive force measurement test. Both test had four groups: Group A (Control group DA without MN); Group B (DA+MN 10%); Group C (DA+MN 20%); and Group D (DA+MN 30%). Results: The mean zone of inhibition was 8.85 ± 0.28 mm for 10% w/w Miconazole Nitrate (MN), 12.95±0.30 mm for 20% w/w MN, and 22.25 ± 0.38 mm for 30% w/w MN. There was a statistically highly significant (P< .001) difference between the groups, with an F value of 1077.8. Conclusion: Within the limitation of the study qualitative anti-microbial property for favorable laboratory performance can be achieved only after the addition of 20% w/w Miconazole Nitrate to denture adhesive paste.

Inhibitory Effect of (-)-myrtenol alone and in combination with antifungal agents on Candida spp.

The aim of this study was to examine the effects of (-)-myrtenol alone and combined with antifungal agents against Candida spp. The Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration of (-)-myrtenol and fluconazole against C. albicans and C. parapsilosis strains was obtained using CLSI guidelines. Combination of (-)-myrtenol with antifungal drugs was determined by checkboard test. The (-) myrtenol showed MIC ranging from 256 to 512 µg/mL against both species assay. And the MFC was 512 µg/mL, demonstrated nature fungicidal (MFC/MIC < 4). In addition, combination of antifungal agents (amphotericin B and fluconazole) and (-) myrtenol showed synergistic and additive effects on strains assays. Based on these results, the present study demonstrates that (-) myrtenol showed strong fungicide activity against Candida spp. In addition, Combination of antifungal agents and (-) myrtenol reduces the effective concentrations of both the agents with synergistic to additive effects. Therefore, (-) myrtenol has potential to be developed into an antifungal agent.

Incidence of Breakthrough Fungal Infections in Acute Myeloid Leukemia Patients Receiving Low Intensity Therapy in the Upfront and Relapsed/Refractory Setting

Introduction: New treatment strategies with low intensity therapy have emerged for acute myeloid leukemia (AML) patients who are not candidates for intensive therapy. To date, there is limited data on the frequency of invasive fungal infections (IFIs) in patients treated with low intensity regimens, and there is no consensus on the most appropriate prophylactic antifungal agent to use in either the newly diagnosed or relapsed/refractory setting. At our institution, fluconazole is the prophylactic antifungal agent of choice for neutropenic patients receiving low intensity therapy, however the appropriateness of fluconazole is being questioned due to the depth and duration of neutropenia observed in these patients. Rates of breakthrough IFIs need to be better characterized to optimize antifungal prophylaxis in this patient population. Methods: This is a retrospective review of AML patients treated with low intensity therapy from January 2017 through May 2020 for both newly diagnosed and relapsed/refractory disease. Patients were included if they received fluconazole as prophylaxis during periods of neutropenia and received at least two cycles of low intensity treatment. Low intensity regimens included hypomethylating agent (HMA) monotherapy or a combination of venetoclax with either a HMA or low dose cytarabine (LDAC). Any patient with a contraindication to fluconazole or those who received prophylaxis with an alternative antifungal agent (i.e. posaconazole, voriconazole, isavuconazole, and micafungin), history of previous IFI, or history of a stem cell transplant were excluded. The primary objective was to determine the incidence of breakthrough IFIs. The secondary objective was to further characterize IFI occurrences as possible, probable or proven using criteria defined by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC). An occurrence of IFI was defined as receipt of any systemic antifungal agent, aside from fluconazole, for four or more days for suspected IFI. Patients were evaluated for antifungal escalation from the time of low intensity treatment initiation through 30 days after treatment discontinuation. Results: Eighty encounters were included for analysis. The median age of the cohort was 73 years (interquartile range [IQR] 67 - 80) and 70% of patients were newly diagnosed (n = 56). HMA/venetoclax was the most commonly utilized regimen (66%, n = 53) followed by HMA monotherapy (29%, n = 23) and LDAC/venetoclax (5%, n = 4). The median number of treatment cycles was 5 (IQR 3 - 9). Nineteen IFI occurrences (24%) were documented, with ten in the newly diagnosed population (18%, n = 10/56) and nine in relapsed/refractory patients (38%, n = 9/24). There were no proven, four probable and fourteen possible IFIs. Of the four probable infections, three were in relapsed/refractory patients. Median times to IFI onset from low intensity treatment initiation were 82 and 80 days for the newly diagnosed and relapsed/refractory populations, respectively. Of the patients with an IFI, 15/19 (79%) were neutropenic at IFI onset. Conclusions: IFIs are a serious complication of AML as these infections are associated with significant morbidity and mortality. With 24% of patients requiring antifungal escalation, our study demonstrates that breakthrough IFIs remain a concern for patients receiving low intensity therapy and fluconazole prophylaxis. Incidence of IFI was higher in the relapsed/refractory setting, which is an expected finding as these patients are typically subjected to multiple lines of therapy, leading to poor hematopoietic reserves and more prolonged periods of profound neutropenia. Additional analysis is needed for determination of risk factors, beyond relapsed/refractory disease, to potentially identify subsets of patients at highest risk of developing IFIs as these patients may benefit from closer monitoring and longer durations of prophylaxis. Given these findings, it is reasonable to consider prophylaxis with an extended spectrum antifungal agent against molds for patients receiving low intensity therapy. Figure 1 Figure 1. Disclosures Ellis: Rafael Pharmaceuticals: Consultancy. Pardee: Karyopharm Pharmaceuticals: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Rafael Pharmaceuticals: Consultancy, Research Funding; Genetech: Membership on an entity's Board of Directors or advisory committees; BMS: Speakers Bureau; Pharmacyclics: Speakers Bureau.

Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1’-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C. krusei. Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.