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A 7-year-old castrated male poodle was brought to the referral Animal Medical Center and diagnosed with diabetes and pancreatitis. One month later, the patient presented with cloudy urine, and ultrasonography revealed a large number of spherical substances. The patient was subsequently diagnosed with fungal cystitis with Candida albicans. Initially, 10.00 mg kg-1 itraconazole was prescribed twice daily for six weeks, and the symptoms of prolonged urination improved; however, the fungal balls persisted in the bladder. The six months later, the patient showed recurrent symptoms, such as dysuria and stranguria; therefore, 5.00 mg kg-1 fluconazole was prescribed twice daily; however, it was not effective. Subsequently, 1.00 mg kg-1 caspofungin once daily was administered for three consecutive days. Finally, the fungal balls in the bladder disappeared. The patient was regularly monitored after completion of treatment and, 17 months later, doing well without recurrence. Few reports exist on the use of caspofungin in veterinary medicine. The recommended dose of caspofungin in dogs remains unknown. In the case of azoleresistant Candida, treatment using caspofungin should be considered; although, additional studies on the established dosing and side effects are needed. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance remains a worldwide issue with a major clinical and economic impact, leading to exceeding mortality, increased frequency of hospitalization and a great burden on the healthcare systems. Vulvovaginitis, especially when due to mixed infections, has emerged as a condition for which appropriate selection of antimicrobial therapy and proper antimicrobial stewardship programs (ASPs) may contribute to minimizing the resistance development. This review discusses the appropriateness of selecting treatment for vulvovaginitis in order to reduce the development of resistance in gynecological practice. Narrative review based on a selection of literature performed according to the Authors' experience and a MEDLINE search using the following keywords: "vaginitis" OR "Candida" OR "fungal infection" AND "antifungal therapy". No limits were applied, but papers were selected for inclusion in this narrative review according to their relevance to the topic, as judged by the Authors. Worldwide, antimicrobial treatment in gynecology and ASPs focuses on prescribing systemic and expensive antifungal drugs, while treatment selection should consider several factors. Recently, topical azoles have been recommended as suitable alternatives to oral systemic azoles, given their similar efficacy in limiting clinical recurrence. In particular, fenticonazole has already been proposed as an alternative to systemic antifungal drugs to limit the onset of resistance. Optimizing the selection of antimicrobial treatment can help reduce the development of resistance in gynecological practice. Given its wide action spectrum and ability to exert antimicrobial activity against fungi, bacteria and mixed infections, fenticonazole may be considered a suitable first-line, empiric therapy for vaginal and mixed infections, avoiding alteration of intestinal microflora and minimizing the risk of selection of drug-resistant microbial strains. [ABSTRACT FROM AUTHOR]

Fungal infections are human infections that topically affect the skin, mucous membranes, or more serious, invasive, and systemic diseases of the internal organs. The design and advancement of the formulation and approach of administration for therapeutic agents depend on many variables. The correlation between the formulations, mode of administration, pharmacokinetics, toxicity and clinical indication must be thoroughly studied for the successful evolution of suitable drug delivery systems. There are several NP formulations that serve as good delivery approaches for antifungal drugs. This paper covers various groups of nanoparticles utilized in antifungal drug delivery, such as phospholipid-based vesicles (nanovesicles), non-phospholipid vesicles, polymeric nanoparticles, inorganic nanoparticles and dendrimers, whereby their advantages and drawbacks are emphasized. Many in vitro or cell culture studies with NP formulations achieve an adequate high drug-loading capacity; they do not reach the clinically significant concentrations anticipated for in vivo studies. Because of this, the transfer of these nano-formulations from the laboratory to the clinic could be aided by focusing studies on overcoming problems related to nanoparticle stability, drug loading, and high production and standardization costs. [ABSTRACT FROM AUTHOR]

Mucormycosis represents a group of life-threatening infections caused by fungi of the order mucorales of subphylum mucormycotina. Due to high vascularity, the maxilla rarely undergoes necrosis. Mucormycosis is an opportunistic fulminant fungal infection, which mainly infects immune-compromised patients. Due to the inhalation of fungal spores, the infection may begin in the nose and paranasal sinuses. Necrosis of hard and soft tissues is due to thrombosis of arteries, which is caused by the inhalation of fungal spores. We report a case of maxillary necrosis by mucormycosis in a COVID-19-recovered patient to emphasize the early diagnosis of this potentially fatal fungal infection. We reviewed the current concepts in the management of mucormycosis and different diseases that can lead to maxillary necrosis. The mortality and morbidity of this lethal fungal infection can be successfully reduced by early diagnosis and quick treatment by the general primary care provider, family physicians, and dentists.

Cryptococcosis is frequently found in immunosuppressed patients. It is also a significant opportunistic infection in non-immunocompromised individuals. In this study, we present a rare case of membranous nephropathy (MN) with pulmonary cryptococcosis. A 33-year-old man with MN was referred to our hospital because of dyspnea and weakness for 1 week. Before the above symptoms occurred, the dose of Cyclosporin A was increased again for relapse of MN. Multiple massive or patchy high-density shadows were present on computed tomography of the lung. Initially the patient underwent empirical anti-bacterial therapy, which turned out to be ineffective. As the results of serum cryptococcal latex agglutination tests were positive, the administration of anti-fungal drugs was prescribed. The results of fungal culture and pathologic examination of the lung tissue revealed the findings consistent with Cryptococcus neoformans. The patient was successfully treated with voriconazole followed by fluconazole with satisfactory result. Therefore, in patients with chronic kidney disease, lung lesions with poor bactericidal effects of cephalosporins need further examination to make sure whether there is pulmonary cryptococcosis. Early diagnosis and treatment might contribute to good results. It is a problem worthy of consideration that whether immunosuppressive agents need to be discontinued or not during antifungal therapy.

Topical delivery of drugs using nanosponges has gained significant attention as a potential strategy for the treatment of fungal infections. Nanosponges, owing to their large surface area, biocompatibility and ability to selectively absorb and retain various molecules, have the potential to enhance the delivery of antifungal drugs to the site of infection. This review focuses on recent developments in the field of topical delivery of antifungal drugs using nanosponges. The review encompasses the various types of nanosponges loaded with different antifungal drugs that achieved preclinical successes and the reasons behind the superiority of nanosponge formulation as anti-fungal drug delivery platforms in terms of their drug loading and release capacities. Additionally, potential applications in areas such as drug delivery and the use of botanical extracts and their phytochemicals together with nanosponges for antifungal use have been cited, along with the current challenges and future directions in the field of nanosponges. [Display omitted] • This paper discusses about highly porous nano sponges. • Nano sponge may be a good delivery device for antifungal drug delivery. • This paper gives a clear view about synthesis, functionalization, and applications. • Future perspective and challenges associated with nano sponges were discussed. [ABSTRACT FROM AUTHOR]

Background and objective: The constant increase of Candida infection and unstopping emergence of drug resistant Candida species is a major concern. Natural medicinal products particularly those of edible plant could be a safe and effective alternative to synthetic substances. Considering their anti-microbial contents, the leave extracts of Anethemgraveolens and Apiumgraveolens have been investigated for their effects against Candida species. Methods: Fresh leaves of Anethem and Apium were collected from Erbil province in Iraq. The leaves were dried then after grinding the ethanol extract was prepared. The radical scavenging activity of extracts was measured via DPPH inhibition activity method. Anti-Candida effect was assessed against C. albicans, C. glabrata, C. krusei, C. tropicalis, C. tamatta, C. parapsiosis, and C. guilliermondii. Standard antifungal drugs were used as control including Nystatin, Clotrimazole, Fluconazole, Ketoconazole, and Miconazole. Results: The highest radical scavenging activity of both extracts was found at 0.2 mg/mL. Both extracts did not affect the growth inhibition of C. krusei, C. tropicalis, and C. tamatta. However, they were significantly effective to the extent of other antifungal drugs against the growth of other Candida species including C. albicans, C. glabrata, C. guillermondii, and C. parapsiosis. Conclusion: The findings of this study suggest that both Apium and Anethem which are widespread vegetable and could have similar anti-Candia effects which can be a great alternative to the commonly used antifungal drugs.

Mucormycosis represents a group of life-threatening infections caused by fungi of the order mucorales of subphylum mucormycotina. Due to high vascularity, the maxilla rarely undergoes necrosis. Mucormycosis is an opportunistic fulminant fungal infection, which mainly infects immune-compromised patients. Due to the inhalation of fungal spores, the infection may begin in the nose and paranasal sinuses. Necrosis of hard and soft tissues is due to thrombosis of arteries, which is caused by the inhalation of fungal spores. We report a case of maxillary necrosis by mucormycosis in a COVID-19-recovered patient to emphasize the early diagnosis of this potentially fatal fungal infection. We reviewed the current concepts in the management of mucormycosis and different diseases that can lead to maxillary necrosis. The mortality and morbidity of this lethal fungal infection can be successfully reduced by early diagnosis and quick treatment by the general primary care provider, family physicians, and dentists. [ABSTRACT FROM AUTHOR]

A 7-year-old castrated male poodle was brought to the referral Animal Medical Center and diagnosed with diabetes and pancreatitis. One month later, the patient presented with cloudy urine, and ultrasonography revealed a large number of spherical substances. The patient was subsequently diagnosed with fungal cystitis with Candida albicans . Initially, 10.00 mg kg -1 itraconazole was prescribed twice daily for six weeks, and the symptoms of prolonged urination improved; however, the fungal balls persisted in the bladder. The six months later, the patient showed recurrent symptoms, such as dysuria and stranguria; therefore, 5.00 mg kg -1 fluconazole was prescribed twice daily; however, it was not effective. Subsequently, 1.00 mg kg -1 caspofungin once daily was administered for three consecutive days. Finally, the fungal balls in the bladder disappeared. The patient was regularly monitored after completion of treatment and, 17 months later, doing well without recurrence. Few reports exist on the use of caspofungin in veterinary medicine. The recommended dose of caspofungin in dogs remains unknown. In the case of azole-resistant Candida , treatment using caspofungin should be considered; although, additional studies on the established dosing and side effects are needed., Competing Interests: No conflict of interest to declare., (© 2024 Urmia University. All rights reserved.)

A 57-year-old male who had been treated for granulomatosis with polyangiitis (GPA) presented with cough and back pain that had persisted for three days. Mild infiltration shadows and nodules were found on computed tomography images at that time. Increase of GPA lesions and/or bacterial pneumonia was initially suspected. However, serum Cryptococcus neoformans antigen was positive and the chest X-ray findings had worsened by the following day despite of appropriate antibiotic treatment. Thus, pneumonia due to C. neoformans was diagnosed because C. neoformans was also isolated blood and lung tissues, and he was treated with antifungal agents: L-AMB and 5-FC, and followed up by chest radiography on a daily basis.

Among the numerous skin diseases, dermatomycosis is the one caused by fungus (parasite) infecting the skin (host). Once diagnosis is made, dermatomycosis can be cured with the use of appropriate anti-fungal drugs. Therefore, it is a much more easily treatable disease compareds with intractable skin diseases. From his own experience, the author shows that dermatomycoses are good subspecialties to deal with because many of them are controllable. At the same time, the author points out that basic research on medically important fungi needs to be done as collaborative studies with basic scientists and dermatology specialists. This brief review covers several topics including diagnostics of medical mycoses, imported medical mycoses, tinea, and cutaneous deep mycoses. [ABSTRACT FROM AUTHOR]

Virulent fungi represent a particularly difficult problem in the infectious disease arena as these organisms are eukaryotes that share many orthologous activities with their human hosts. The fact that these activities are often catalyzed by conserved proteins places additional demands on development of pharmacological strategies for specifically inhibiting target fungal activities without imposing undesirable secondary effects on the host. While deployment of a limited set of anti-mycotics has to date satisfied the clinical needs for treatment of fungal infections, the recent emergence of multi-drug resistant fungal 'superbugs' now poses a serious global health threat with rapidly diminishing options for treatment. This escalating infectious disease problem emphasizes the urgent need for development of new classes of anti-mycotics. In that regard, Sec14 phosphatidylinositol transfer proteins offer interesting possibilities for interfering with fungal phosphoinositide signaling with exquisite specificity and without targeting the highly conserved lipid kinases responsible for phosphoinositide production. Herein, we review the establishment of proof-of-principle that demonstrates the feasibility of such an approach. We also describe the lead compounds of four chemotypes that directly target fungal Sec14 proteins. The rules that pertain to the mechanism(s) of Sec14 inhibition by validated small molecule inhibitors, and the open questions that remain, are discussed – as are the challenges that face development of next generation Sec14-directed inhibitors. [ABSTRACT FROM AUTHOR]

Nikkomycin Z (NikZ) is a chitin synthase inhibitor with activity against Coccidioides species that is being developed as a first-in-class orphan product for treatment of coccidioidomycosis. It has previously been shown to reduce lethal respiratory infections in mice to undetectable levels when treatment is begun 48 hours after infection. The studies described here focus on bracketing NikZ doses for phase 2 and 3 clinical trials, using an established mouse respiratory infection as a model and starting treatment 120 hours after infection. A dose of 80 mg/kg/day, divided into 2 doses, nearly eradicated infection, and larger doses did not improve fungal clearance. Increasing the duration of treatment from 1 week to 3 weeks resulted in a greater percentage of culture-negative mice. Comparative data show that plasma levels of NikZ that nearly eradicate Coccidioides in mice are achievable in patients and provide a plausibly effective dose range for initial phase 2 clinical studies. [ABSTRACT FROM AUTHOR]

Abstract: Small-angle neutron scattering (SANS) studies have been performed to study the structural changes induced in the membranes of vesicles prepared (by thin film evaporation) from phospholipid and mixed phospholipid–sterol mixtures, in the presence of different concentrations and different aggregation states of the anti-fungal drug, amphotericin B (AmB). In the majority of the experiments reported, the lipid vesicles were prepared with the drug added directly to the lipid dispersions dissolved in solvents favouring either AmB monomers or aggregates, and the vesicles then sonicated to a mean size of ~100nm. Experiments were also performed, however, in which micellar dispersions of the drug were added to pre-formed lipid and lipid–sterol vesicles. The vesicles were prepared using the phospholipid palmitoyloleoylphosphatidylcholine (POPC), or mixtures of this lipid with either 30mol% cholesterol or 30mol% ergosterol. Analyses of the SANS data show that irrespective of the AmB concentration or aggregation state, there is an increase in the membrane thickness of both the pure POPC and the mixed POPC-sterol vesicles—in all cases amounting to ~4Å. The structural changes induced by the drug''s insertion into the model fungal cell membranes (as mimicked by POPC-ergosterol vesicles) are thus the same as those resulting from its insertion into the model mammalian cell membranes (as mimicked by POPC-cholesterol vesicles). It is concluded that the specificity of AmB for fungal versus human cells does not arise because of (static) structural differences between lipid–cholesterol-AmB and lipid–ergosterol-AmB membranes, but more likely results from differences in the kinetics of their transmembrane pore formation and/or because of enthalpic differences between the two types of sterol-AmB complexes. [Copyright &y& Elsevier]

Abstract: This paper describes the use of a polished silver solid amalgam electrode (p-AgSAE), evaluation of its electrochemical behaviour and the development of an electroanalytical procedure for the determination of ketoconazole (KC) in pharmaceutical formulations. The experimental and voltammetric conditions were evaluated and the best responses were obtained in BR buffer (pH 12.0) with f =100s−1, a =25mV and ΔE s =2mV. Under these conditions, the voltammetric response of KC presented a well-defined and quasi-reversible reduction peak at around −1.46V vs. Ag/AgCl/Cl− at 3.0molL−1. Analysis of a purified laboratory electrolyte using the proposed methodology allowed for responses that were directly proportional to KC concentration, and the analytical sensitivity was comparable to published results using mercury electrodes and solid surfaces, such as carbon paste, gold and platinum electrodes. The recovery percentages in pure electrolyte, as well as tablet, shampoo and cream samples, showed values from 90 to 105%, demonstrating that the voltammetric methodology proposed is suitable for determining KC in complex samples. The method has excellent robustness and specificity for analytical purposes, minimises toxic residues due to the use of liquid mercury, and avoids adsorptive processes related to the use of other solid surfaces. [Copyright &y& Elsevier]

Twenty-eight incapacitated individuals (average 43 years old, 7 males, 21 females, range 12-70) exposed to molds and mycotoxins were studied and treated with a protocol of cleaning up or changing their environment to be mold free. Injections of the optimum dose of antigens were given as part of the treatment protocol as was oral and intravenous (i.v.) antioxidants; heat depuration (sauna); physical therapy with massage and exercise under environmentally controlled conditions; oxygen therapy at 4-8 L/min for 2 hours with a special woodgrade cellophane reservoir and a glass oxygen container. Many patients were sensitive to plastics; therefore, exposures to these were kept to a minimum. Autogenous lymphocytic factor was given as an immune modulator. Of 28 patients, 27 did well and returned to work. One patient improved but did not return to work during the period of study. [ABSTRACT FROM AUTHOR]

CAY-1, a novel saponin from Capsicum frutescens (commercially known as cayenne pepper) was investigated to determine its in vitro antifungal activity, mechanism of action and mammalian cell cytotoxicity. CAY-1 was active against 16 different fungal strains, including Candida spp. and Aspergillus fumigatus [minimum inhibitory concentrations (MIC) ranging from 4 to 16 µg ml -1 ], and was especially active against Cryptococcus neoformans (90% inhibition at 1 µg ml -1 ). Synergistic activity was also observed between CAY-1 and amphotericin B against Candida albicans and A. fumigatus . No significant cytotoxicity was demonstrated when CAY- 1 was tested against 55 mammalian cell lines at up to 100 µg ml -1 . Importantly, CAY-1 appears to act by disrupting the membrane integrity of fungal cells. [ABSTRACT FROM AUTHOR]

A 57-year-old male who had been treated for granulomatosis with polyangiitis (GPA) presented with cough and back pain that had persisted for three days. Mild infiltration shadows and nodules were found on computed tomography images at that time. Increase of GPA lesions and/or bacterial pneumonia was initially suspected. However, serum Cryptococcus neoformans antigen was positive and the chest X-ray findings had worsened by the following day despite of appropriate antibiotic treatment. Thus, pneumonia due to C. neoformans was diagnosed because C. neoformans was also isolated blood and lung tissues, and he was treated with antifungal agents: L-AMB and 5-FC, and followed up by chest radiography on a daily basis. [ABSTRACT FROM AUTHOR]

Leishmaniasis is an infectious disease caused by protozoal parasites belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and health condition of patients. It can range from single cutaneous lesion until deadly visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and in some cases, the second-line drug, amphotericin B is used. Beside the toxicity of both drugs, parasites can be resistant to antimonial in some areas of the world. This makes fundamental the characterization of new drugs with leishmanicidal effect. Thus, the aim of the present work was to study the leishmanicidal activity of drugs able to interfere with ergosterol pathway (fenticonazole, tioconazole, nystatin, rosuvastatin and voriconazole) against promastigote and amastigote forms of L.(L.) amazonensis, L.(V.) braziliensis and L.(L.) infantum, and its impact on morphological and physiological changes in L.(L.) amazonensis or in host macrophages. We observed that fenticonazole, tioconazole and nystatin drugs eliminated promastigote and intracellular amastigotes, being fenticonazole and nystatin the most selective towards amastigote forms. Rosuvastatin and voriconazole did not present activity against amastigote forms of Leishmania sp. In addition, the drugs with leishmanicidal activity interfered with parasite mitochondrion. Although drugs did not stimulate NO and H2O2, specially fenticonazole was able to alkalize infected host macrophages. These results suggest well established and non-toxic antifungal drugs can be repurposed and used in leishmaniasis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)