Onychomycosis is a common nail disease caused by fungi. The primary pathogens are dermatophytes; however, yeasts, non-dermatophyte moulds, and mixed fungal populations may also contribute to the ...development of a recalcitrant condition, usually accompanied by difficulties in everyday life and severe emotional stress. Treatment failure and relapse of the infection are the most frequent problems, though new issues have become the new challenges in the therapeutic approach to onychomycosis. Resistance to antifungals, an increasing number of comorbidities, and polydrug use among the ageing population are imperatives that impose a shift to safer drugs. Topical antifungals are considered less toxic and minimally interact with other drugs. The development of new topical drugs for onychomycosis is driven by the unmet need for effective agents with prolonged post-treatment disease-free time and a lack of systemic impact on the patients’ health. Efinaconazole, Tavaborole, and Luliconazole have been added to physicians’ weaponry during the last decade, though launched on the market of a limited number of countries. The pipeline is either developing new products (e.g., ME-1111 and NP213) with an appealing combination of pharmacokinetic, efficacy, and safety properties or reformulating old, well-known drugs (Terbinafine and Amphotericin B) by using new excipients as penetration enhancers.
An assessment was made of the efficacy and renal safety of amphotericin B lipid complex (ABLC) in the treatment of patients with invasive fungal infections caused by moulds other than Aspergillus ...species, on the basis of a retrospective analysis of data from the Collaborative Exchange of Antifungal Research (CLEAR) database. Data from CLEAR for 64 patients with zygomycosis were published previously. The database was further queried and yielded results for 28 patients with fusariosis and 84 patients infected with other non-Aspergillus moulds. Of 26 patients with fusariosis whose results could be evaluated, 46% (n = 12) were cured or improved, and an additional 12% (n = 3) were stable. Of 79 patients infected with other non-Aspergillus moulds whose results could be evaluated, 61% (n = 48) were cured or improved, and an additional 15% (n = 12) were stable. In an area with little guidance for therapy, the CLEAR data indicate that ABLC can be an effective broad-spectrum treatment choice for several invasive and refractory non-Aspergillus mould infections.
The increased numbers of patients with compromised immune systems in the last three decades have increased the chances of life-threatening fungal infections. Numerous antifungal drugs have been ...developed in the last 20 years to treat these infections. The largest group, the azoles, inhibits the synthesis of fungal sterols. The use of these fungistatic azoles has subsequently led to the emergence of acquired azole resistance. The most common mechanisms that result in azole resistance include the overexpression or mutation of the azole target enzyme, and overexpression of drug transporters that are responsible for azole efflux from cells. Additional, less-frequent mechanisms have also been identified. Understanding azole resistance mechanisms is crucial for current antifungal treatment and for the future development of new treatment strategies.
Summary
Background
The incidence of fungal keratitis has increased in recent years. While the epidemiology and clinical roles of various Candida and Fusarium species have been relatively ...well‐identified in infections of the eye, data regarding keratitis caused by Aspergillus species are scant. Accurate and rapid diagnosis is important for successful management of this infection.
Objectives
To present the first molecular epidemiological data from Mexico during a 4‐year period of cases admitted with Aspergillus keratitis to a tertiary care eye institution in Mexico City.
Patients/Methods
A total of 25 cases of keratitis were included in the study. Aspergillus isolates were identified by sequencing the calmodulin gene. Antifungal susceptibility was tested according to CLSI.
Results
The aetiological agents belonged to Aspergillus flavus (n = 13), Aspergillus effusus (n = 1), Aspergillus tamarii (n = 4), Aspergillus sydowii (n = 1), Aspergillus protuberus (n = 3) and Aspergillus terreus (n = 3). All strains had low minimum inhibitory concentrations (MICs) of itraconazole and voriconazole (VCZ). Amphotericin B and natamycin showed moderate elevated MICs.
Conclusions
Early diagnosis and application of topical VCZ 1% were associated with good outcome. Monitoring of local epidemiological data plays an important role in clinical practice.
Since our study showed that sulfone derivatives’ action mode creates a lesser risk of inducing widespread resistance among Candida spp., we continued verifying sulfones’ antifungal activity using the ...following newly synthesized derivatives: bromodichloromethy-4-hydrazinyl-3-nitrophenyl sulfone (S1), difluoroiodomethyl-4-hydrazinyl-3-nitrophenyl sulfone (S2), and chlorodifluoromethyl-4-hydrazinyl-3-nitrophenyl sulfone (S3). As the mechanism by which sulfones gain access to the cytoplasm has not been elucidated yet, in order to track S1-3, we coupled their hydrazine group with BODIPY (final S1-3 BODIPY-labelled were named SB1-3). This approach allowed us to follow the vital internalization and endocytic routing of SB1-3, while BODIPY interacts primarily with fungal surfaces, thus confirming that S1-3 and their counterparts SB1-2 behaved as non-typical agents by damaging the cell membrane and wall after being endocytosed (SB1-3 fluorescence visible inside the unlysed sessile cells). Thus greatly decreasing the likelihood of the appearance of strains resistance. Core sulfones S1-3 are a promising alternative not only to treat planktonic C. albicans but also biofilm-embedded cells. In the flow cytometric analysis, the planktonic cell surface was digested by S1-3, which made the externalized PS accessible to AnnexinV binding and PI input (accidental cell death ACD). The occurrence of ACD as well as apoptosis (crescent-shaped nuclei) and anoikis of sessile cells (regulated cell death by 100%-reduction in attachment to epithelium) was assessed through monitoring the AO/PI/HO342 markers. CLSM revealed the invasion of S1-3 and SB1-3 in C. albicans without inducing cell lysis. This was a novel approach in which QCM-D was used for real-time in situ detection of viscoelastic changes in the C. albicans biofilm, and its interaction with S1 as a representative of the sulfones tested. S1 (not toxic in vivo) is a potent fungicidal agent against C. albicans and could be administered to treat invasive candidiasis as a monotherapy or in combination with antifungal agents of reference to treat C. albicans infections.
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•Sulfones are active against planktonic and biofilm-embedded C. albicans cells.•BODIPY-labelled Sulfones display endocytic routing in C. albicans.•Sulfones lead to accidental cell death, apoptosis, and anoikis in C. albicans.•Real time treatment with Sulfone influences the biofilm remodelling in the QCM-D study.
Elasmobranchs currently constitute an important part of the animal collection of many aquariums worldwide. Their maintenance under human care has allowed us to describe and identify new pathogens and ...diseases affecting them, as well as to determine different treatments for these diseases. Great advances in elasmobranch husbandry have been developed.
A search was performed on scientific databases as PubMed and other specialized sources (IAAAM archive).
Little information on pharmacotherapeutics is available in this taxonomic group, and treatments lack a scientific base and instead are frequently dependent on empirical knowledge. Pharmacokinetic studies are the first step to determining therapeutic protocols that are safe and effective. The available bibliography shows that a majority of the mycoses recorded in cartilaginous fish are severe, aggravated by the fact that the antifungal treatments administered, following the guidelines used for teleost species, are ineffective in elasmobranchs. Azoles appear to be a promising group of antifungals for use in treating systemic mycoses in sharks and rays.
Based on the findings of this review, it is essential to investigate the pharmacokinetics of the different antifungals in these species in order to provide therapeutic options for fungal infections in cartilaginous fish.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Polyene macrolides are potent antifungal agents that are also active against parasites, enveloped viruses and prion diseases. They are medically important as antifungal antibiotics but their ...therapeutic use is limited by serious side effects. In recent years there has been considerable progress in genetic analysis and manipulation of the streptomycetes that produce nystatin, amphotericin B, candicidin, pimaricin and rimocidin/CE-108-related polyenes. This has led to engineered biosynthesis of several new polyenes that are not easily obtained as semi-synthetic derivatives. This review summarises recent advances made since the subject was last reviewed in 2003. Polyene biosynthesis generally involves assembly and cyclisation of a polyketide chain, followed by oxidative modifications and glycosylation of the macrolactone ring. New derivatives have been obtained by engineering both early and late stages of polyene biosynthetic pathways. These compounds have allowed more detailed investigations of structure-activity relationships and some are likely to show improvements in therapeutic index. The biosynthetic approach is already yielding sufficient material for testing the toxicity and activity of new compounds, thus opening possibilities for discovery of leads for development of effective and safe antifungal and antiparasitic agents.
We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with ...neutropenia and unresolved fever after ⩾3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/kg·d) or amphotericin B (0.8 mg/kg·d) for ⩽14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B—treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.
The incidence of invasive aspergillosis is markedly increasing, and mortality remains dismal. Previously there were only 2 antifungals with activity against Aspergillus, but over the last few years ...there has been an explosion of newer agents and reformulations of older antifungals. Exploration has also begun with immunotherapy, with use of cytokines and granulocyte transfusions alone or in combination with antifungal therapy. This review will detail the available in vitro, in vivo, and clinical experience with the newer antifungal and immunomodulatory therapies in development for treatment of invasive aspergillosis.
Host Defenses Against Zygomycetes Roilides, Emmanuel; Kontoyiannis, Dimitrios P.; Walsh, Thomas J.
Clinical infectious diseases,
02/2012, Letnik:
54, Številka:
suppl_1
Journal Article
Recenzirano
Odprti dostop
Mucormycosis is a devastating disease and can occur in patients with a variety of risk factors, the most important of which are immunosuppression, anatomic barrier breakdown, iron overload, and ...hyperglycemia/acidosis. Similarly to what occurs with Aspergillus, the host stimulates an innate immune response against the challenging sporangiospores and invading hyphae of Zygomycetes. This article discusses the host defense to different Zygomycetes, its augmentation, and its subsequent impact on the outcome of mucormycosis.
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