Novel antifungal agents in clinical trials

Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics. The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics. This review highlights promising investigational antifungal agents in clinical phases of development: fosmanogepix, ibrexafungerp, rezafungin, encochleated amphotericin B, oteseconazole (VT-1161), VT-1598, PC945, and olorofim. We discuss three first-in-class members of three novel antifungal classes, as well as new agents within existing antifungal classes with improved safety and tolerability profiles due to enhanced pharmacokinetic and pharmacodynamic properties.

Zein-Based Films Containing Monolaurin/Eugenol or Essential Oils with Potential for Bioactive Packaging Application

Zein is renewable plant protein with valuable film-forming properties that can be used as a packaging material. It is known that the addition of natural cross-linkers can enhance a film’s tensile properties. In this study, we aimed to prepare antimicrobial zein-based films enriched with monolaurin, eugenol, oregano, and thyme essential oil. Films were prepared using the solvent casting technique from ethanol solution. Their physicochemical properties were investigated using structural, morphological, and thermal techniques. Polar and dispersive components were analyzed using two models to evaluate the effects on the surface free energy values. The antimicrobial activity was proven using a disk diffusion method and the suppression of bacterial growth was confirmed via a growth kinetics study with the Gompertz function. The films’ morphological characteristics led to systems with uniform distribution of essential oils or eugenol droplets combined with a flat-plated structure of monolaurin. A unique combination of polyphenolic eugenol and amphiphilic monoglyceride provided highly stretchable films with enhanced barrier properties and efficiency against Gram-positive and Gram-negative bacteria, yeasts, and molds. The prepared zein-based films with tunable surface properties represent an alternative to non-renewable resources with a potential application as active packaging materials.

Environmental and Fecal Indicator Organisms on Fruit Contact Surfaces and Fruit from Blueberry Mechanical Harvesters

Although previous studies have examined microbial loads on food contact surfaces in blueberry packing plants, there is currently no information regarding microbial risks associated with mechanical berry harvesters used in commercial blueberry production. In this study, we surveyed up to nine fruit contact surfaces on seven mechanical harvesters in each of 2015 and 2016 in the field. These surfaces included the shaking rods at the front of the harvester, the sidewalls of the harvesting tunnel behind the shaking mechanism, the catcher plates collecting the detached berries, horizontal and vertical fruit conveyor belts, and berry lugs collecting the fruit at the back of the harvester. Swab samples were collected from each surface three times a day (morning, noon, and evening) and assessed for environmental and fecal indicator organisms including total aerobes, total yeasts and molds, coliforms and fecal coliforms, and enterococci. At the same time points, fruit samples were assessed for microbial loads before the fruit entered each harvester and after they exited the harvester. Results showed statistically significant differences in microbial loads among harvester surfaces, whereas the effect of sampling time was generally not significant. High levels of total aerobes and total yeasts and molds were recorded, especially on horizontal surfaces and/or those located at the bottom of the harvester such as the lower sidewall, the catcher plates, and the horizontal conveyor belt. These surfaces therefore should be targeted by cleaning and sanitization practices. There was also statistical evidence that passage through the harvester may increase the levels of the environmental microorganisms on fruit in the field. In contrast, fecal indicator organisms such as fecal coliforms and enterococci were detected only sporadically and at very low densities on harvester surfaces and blueberry fruit, and there was no evidence that passage through the harvester increased their levels on the fruit. Berry lugs consistently harbored microbial loads, and given their movement back and forth between the field and the packing plant, deserve particular attention with regard to cleaning, sanitization, and storage protocols.

Evaluation of antimicrobial compounds to inhibit growth of select Gram-positive pathogenic or antimicrobial resistant bacteria in air-exposed silage

Spoiled silages can harbor pathogenic and antimicrobial-resistant microbes. The potential of some antimicrobial additives to inhibit certain pathogenic and antimicrobial-resistant bacteria in air-exposed silage was measured using pure and mixed bacterial cultures. With pure cultures, laurate and monolaurin (5 mg·mL−1) caused decreases (P < 0.05) of 4 to >7 log10 colony-forming units (CFU)·mL−1 in Listeria monocytogenes and Enterococcus faecalis compared to controls. Ten-fold higher amounts of these inhibitors were needed to equivalently decrease staphylococci. 2-Nitropropanol (1 mg·mL−1) decreased (P < 0.05) E. faecalis and L. monocytogenes 2.9–3.8 and 2.4–7.2 log10 CFU·mL−1 after 6 and 24 h incubations, respectively. In air-exposed whole-plant corn silage the inhibitors caused decreases, although not necessarily significant, of 0.7–2.2 log10 CFU·mL−1 in L. monocytogenes, staphylococci and culturable aerobes after 24 h incubation, with modest yet significant (P < 0.05) inhibition (<0.1–0.3 log10 CFU·mL−1) of yeasts and molds. Tests for carry-over effects against ruminal microbes revealed laurate, monolaurin, and 2-nitropropanol inhibited methanogenesis by >50% (P < 0.05) after 24 h incubation and inhibited L. monocytogenes and enterococci. The antimicrobial activities exhibited by these compounds may yield opportunities to optimize their use to rescue spoiled silages.

Microbiological stability of homeopathic medicines using purified water as vehicle

Background: Homeopathic medicines are prepared in homeopathic pharmacies. This leads to freedom of prescription but requires more knowledge of the clinicians to achieve the best results. Preparations made of purified water receive a validity of 24 hours, but there are prescriptions for up to 30 days. This contradiction raises tensions among physicians, pharmacists and patients. Aims: to evaluate the increase in microbiological contamination in homeopathic medicines using purified water as vehicle compared with the microbiological stability of purified water. Contribute to the quality of homeopathic medicine and treatment. Methodology: daily microbiological analysis for one week to assess the growth of heterotrophic bacteria, Pseudomonas, yeasts and molds. The reference used was the USP 32/NF 27 and the Brazilian Pharmacopoeia 5th edition. Results: there was a higher growth of microorganisms on the medicine, compared with purified water. From the 2nd day on, this growth has been beyond the legal limits. Discussion: medicines for oral use are not sterile preparations, but they must remain stable during its shelf life. Our results indicate that contamination occurs from the earliest days of use. This shows the need to change the prescription in relation of the vehicle, to ensure hygiene and avoid potential contamination of the patient. It is necessary to prevent conflict of information between pharmacists and patients, and the contradiction of the doctor's advice, besides the potential risk of responsibility to be attributed to the pharmacy. It is necessary to promote a discussion between pharmacists and clinicians, to spread this information for those that prescribe. Conclusion: there was an increased of microbiological contamination of the medicines dispensed in purified water, which harms the quality of homeopathic medicine and homeopathic treatment.

The Effect of Dietary Dry Distilled Rose Petals or Dihydroquercetin Supplementation on the Oxidative Stability and Quality of Lamb Muscles and Fat

The study's objective was to determine the changes in oxidative stability of m. Longissimus dorsi, m. Semimembranosus and perirenal adipose tissue from lambs fed a diet supplemented by 7.5 mg dihydroquercetin/kg life wight/d or 545 mg dry distilled rose petals (DDRP)/kg life wight/d.The experiments were performed with 30 male lambs aged 65 days. They were divided into three groups of 10 animals fed 50 days ad libitum: the control group (with ground alfalfa + granulated compound feed) and two experimental ones (with the same diet + phytonutrients). Samples stored 7 days at 0-4°C were examined. After 7 d of storage in both muscles, the addition of 545 mg DDRP/kg life wight/d contributed to the reduction of α-aminoacidic nitrogen with approximately 0.5 mg Leu/g and the FFA with 0.5-2%. The addition of 7.5 mg dihydroquercetin contributed to the reduction of TBARS with 0.14-0.21 mg MDA/kg, the total color difference, and a slight increase in the share of the MUFA more pronounced in m. Longissimus dorsi. The reduction of aerobic plate count and total yeasts and molds count were determined too. Further studies with higher doses of phytonutrient’s supplementation are needed to determine if it will provoke a more pronounced oxidative stability.

Effectiveness of Goji Berries (Lycium barbarum) Extract and Some Nanoparticles Loaded on Gelatin Film on Microbial Content of Labneh

This study was conducted to evaluate the effect of Lycium barbarum extract, Chitosan nanoparticles (ChNPs) and Nanotitanium dioxide (TiO2 NPs) loaded on Gelatin films on the microbial content of labneh during different storage periods. The samples were divided into seven treatments which included (T1) non-coated labneh, (T2) labneh coated with gelatin membranes, (T3) labneh coated with gelatin membranes and Lycium barbarum extract, (T4) labneh coated with gelatin films and ChNPs, (T5) labneh coated with gelatin films treated TiO2NPs, (T6) Labneh coated with gelatin films, Lycium barbarum and ChNPs, (T7) Labneh coated with gelatin films, Lycium barbarum and TiO2 NPs. The total number of bacteria decreased after loading with the membranes for each specific period of time, and the treatment with T7 was the best, as the total number of bacteria decreased to 9.93 log/gm compared to the two controls (T1, T2), which amounted to (15.58, 13.47 log/gm) after 14 days of storage, respectively. While the numbers of Lipolytic and Proteolytic bacteria, yeasts and molds did not show any growth at the time of one day, with the prolonged storage period, the gradual increase in the total count of bacteria occurred for all treatments, it reached the highest numbers at the time of 14 days. Treatment T7 was the best in reducing the numbers of both lipolytic and proteinolytic bacteria, as well as yeasts and molds.

A meta-analysis of topical antifungal drugs to treat atopic dermatitis

Review question / Objective: Various bacteria and fungi colonize the skin surface of patients with AD. The colonized fungi mainly include Malassezia, non-Malassezia yeasts, and molds. Among them, Malassezia occupies 63%~86% of the fungal colonization community on the skin surface of AD patients. Although the relationship between the level of Malassezia on the skin surface and disease severity remains controversial, many studies have shown that the level of serum anti-Malassezia-specific immunoglobulin E (IgE) antibodies in AD patients is related to the disease severity, especially in patients with AD in the head and neck. The specific mechanism by which Malassezia causes or aggravates AD is unclear, but damage to the skin barrier in AD patients is a key component of the mechanism. The presence of Malassezia on the skin also seems to change its barrier function, resulting in more Malassezia and its antigens colonizing the skin surface area that is exposed to the immune system. This produces a large number of specific IgE antibodies and cytokines to aggravate the disease.

Microbiological, sensory, and physicochemical quality of curd cheeses originating from direct sales

Background and Aim: Curd cheeses are characteristic elements of the dairy assortment, mainly in Central and Eastern European countries, and constitute a numerous and diverse group of dairy products. The aim of the study was to assess the physicochemical, microbiological, and sensory quality of curd cheeses available in marketplaces in Lublin, where they were purchased through direct sales from producers. Materials and Methods: The research material was household-produced curd cheese purchased 4 times (at 2-week intervals) from three producers. The physicochemical parameters (i.e., the total protein and fat content, active acidity, and titratable acidity) were determined in the cheeses. Microbiological assays were performed to evaluate the total number of bacteria (on milk agar), the number of yeasts and molds (on Sabouraud medium), and the number of coliform bacteria (on MacConkey medium). A general sensory evaluation was performed by a five-person panel, who assessed the appearance and color, texture, flavor, and aroma of the samples. Results: The cheeses exhibited significant differences in their protein and fat contents, but these values were within the allowable limits. Most of the evaluated cheeses had normal levels of active and titratable acidity; substantially lower titratable acidity and higher pH values were detected only in the samples from supplier A. The total number of bacteria in the curd cheese samples was high (3.2×108 colony-forming units [cfu]×g-1 cheese) and varied substantially (from 3.6×107 to 8.6×108 cfu×g-1). The growth of Gram-negative bacterial colonies on MacConkey medium was observed in the samples from suppliers B and C (5.5×103 and 1.7×104 cfu×g-1, respectively), which is an undesirable phenomenon. The number of colonies cultured on Sabouraud medium and identified as yeast-like microorganisms ranged from 1.8×104 (product from supplier A) to 4.9×105 cfu×g-1 (cheese from supplier C). The scores in the sensory evaluation of the tested curd cheeses were low. The highest mean scores were achieved for appearance and color (4.25-4.45 points). Conversely, flavor and aroma received the lowest score (3.17 points). The highest scores for both the overall assessment and each parameter separately were awarded to the curd cheese produced by supplier A. Conclusion: Our results suggest poor hygienic conditions during milk collection and processing, as well as during the distribution of these dairy products. Altogether, the purchase of products from direct sales may be associated with risks related to poor consumer health and food quality.