Antifungal Agents

We studied a series of test conditions in a microtiter system to define the optimal method for determining the susceptibility of Cryptococcus neoformans to antifungal agents. Twenty-one isolates of C. neoformans were grown for 24 or 48 h in four chemically defined media: yeast nitrogen base (BYNB 7); RPMI 1640; synthetic amino acid medium--fungal (SAAMF), buffered at pH 7.0 to select the medium that best supported growth of this fastidious yeast; and yeast nitrogen base, pH 5.4 (YNB 5.4). Maximum growth of C. neoformans, at 35 degrees C, was obtained in YNB 5.4, with the next highest growth levels in BYNB 7, SAAMF, and RPMI. Growth at 24 h was uniformly poor in all media and lacked reproducibility. In contrast, incubation for 48 h gave adequate growth with low standard deviations, and 48 h was selected as the optimal incubation period for this study. Comparison of the relationship between growth kinetics and initial inoculum size for eight cryptococcal isolates showed that 10(4) cel...

Phenyllactic acid (PLA) has recently been found in cultures of Lactobacillus plantarum that show antifungal activity in sourdough breads. The fungicidal activity of PLA and growth inhibition by PLA were evaluated by using a microdilution test and 23 fungal strains belonging to 14 species of Aspergillus, Penicillium, and Fusarium that were isolated from bakery products, flours, or cereals. Less than 7.5 mg of PLA ml ؊1 was required to obtain 90% growth inhibition for all strains, while fungicidal activity against 19 strains was shown by PLA at levels of <10 mg ml ؊1 . Levels of growth inhibition of 50 to 92.4% were observed for all fungal strains after incubation for 3 days in the presence of 7.5 mg of PLA ml ؊1 in buffered medium at pH 4, which is a condition more similar to those in real food systems. Under these experimental conditions PLA caused an unpredictable delaying effect that was more than 2 days long for 12 strains, including some mycotoxigenic strains of Penicillium verrucosum and Penicillium citrinum and a strain of Penicillium roqueforti (the most widespread contaminant of bakery products); a growth delay of about 2 days was observed for seven other strains. The effect of pH on the inhibitory activity of PLA and the combined effects of the major organic acids produced by lactic acid bacteria isolated from sourdough bread (PLA, lactic acid, and acetic acid) were also investigated. The ability of PLA to act as a fungicide and delay the growth of a variety of fungal contaminants provides new perspectives for possibly using this natural antimicrobial compound to control fungal contaminants and extend the shelf lives of foods and/or feedstuffs.

We have previously reported the identification of a small, basic and cysteine-rich antifungal peptide (AcAFP) secreted by Aspergillus clavatus and shown its ability to prevent growth of various human-and plant-pathogenic filamentous fungi. In this study, we sought to determine the physiological/microbiological requirements to enhance the AcAFP production and the conditions influencing its stability. The maximum of AcAFP production was obtained when A. clavatus was grown on 2% glycerol as sole carbon source and 100 mM NaCl. The AcAFP expression was shown to be influenced by pH, being suppressed under acidic (pH 5) and strongly induced under alkaline conditions. The activity of the purified AcAFP was not affected by temperature; it loosed approximately 20% of its activity after 3 h at 100°C and was efficient through a large pH range (pH 5-12) with an optimum at pH 8. AcAFP activity decreased at high ionic strength and in the presence of 10 mM of divalent cations (Mn 2+ , Fe 2+ and Ca 2+ ).

ACE-Is might be substituted with other agents for controlling co-morbid diseases before and during chemotherapy to reduce delayed CINV. However, we need further trials in which association between ACE-Is and CINV are investigated. We consider that CINV, especially delayed CINV is a serious toxicity which might upset patients' quality of life. If there is a relationship between ACE-Is and enhancement of CINV, we should prefer potent emesis prophylaxes and antiemetic support in cancer patients who will receive both ACE-Is and emetogenic chemotherapy.

Macrocyclic complexes of Mn(II) were synthesized by template condensation using 2,6-diaminopyridine and diethylenetriamine with malonic, succinic, glutaric and adipic acids. The reaction proceeded smoothly to completion. These 16- to 24-membered N(6), but behaving as tetradentate, macrocyclic complexes were characterized by elemental analyses, molecular weight determinations, infrared, electronic, mass and X-ray spectral analyses. The elemental analyses are consistent with the formation of complexes [Mn(N(6)L(n))Cl(2)]. All the complexes are stable and monomeric in nature, as indicated by the molecular weight determinations. The spectral studies confirmed the proposed framework of the new macrocyclic complexes and indicated an octahedral geometry around the central metal atom. The complexes were screened in vitro against a number of pathogenic fungi and bacteria to assess their growth-inhibiting potential. The testicular sperm density, sperm morphology, sperm motility, density of ca...

Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and other filamentous fungi from the SECURE trial. Two hundred and thirty one patients who received the clinical dosing regimen and had exposure parameters were included in this analysis. The primary drug exposure parameters included were predicted trough steady-state plasma concentrations, predicted trough concentrations after 7 and 14 days of drug administration, and area under the curve estimated at steady state (AUCss). The exposure parameters were analyzed against efficacy endpoints that included: all-cause mortality through Day 42 in the intent-to-treat (ITT) and modified ITT population, data-review committee (DRC)-adjudicated overall respons...

Pytiriasis versicolor is an infectious disease caused by several Malassezia species which has a tendency to become relapsing or chronic. This study was conducted in an attempt to investigate the clinical course of pityriasis versicolor with regard to the number of relapses after a 12-month therapy and correlate this number with isolates of Malassezia species. 102 patients with clinical and laboratory diagnosis of pityriasis versicolor were monitored for 12 months to investigate the number of relapsing episodes of the disease. After appropriate treatment, pityriasis versicolor presented three types of clinical course: pityriasis versicolor without relapsing episodes (32.35%), relapsing pityriasis versicolor with one to four relapsing episodes (52.94% ) due to associated predisposing factors, and chronic pityriasis versicolor with more than four relapsing episodes (14.70%) with no relation to predisposing factors. The clinical course of pityriasis versicolor varied according to the nu...

Overview: Dermatophytosis, usually caused by Microsporum canis, is the most common fungal infection in cats worldwide, and one of the most important infectious skin diseases in this species. Many adult cats are asymptomatic carriers. Severe clinical signs are seen mostly in kittens or immunosuppressed adults. Poor hygiene is a predisposing factor, and the disease may be endemic in shelters or catteries. Humans may be easily infected and develop a similar skin disease. Infection: Infectious arthrospores produced by dermatophytes may survive in the environment for about a year. They are transmitted through contact with sick cats or healthy carriers, but also on dust particles, brushes, clothes and other fomites. Disease signs: Circular alopecia, desquamation and sometimes an erythematous margin around central healing (‘ringworm’) are typical. In many cats this is a self-limiting disease with hair loss and scaling only. In immunosuppressed animals, the outcome may be a multifocal or ge...

The emergence of strains of multidrug-resistant Gram-negative bacteria mandates a search for new types of antimicrobial agents. Alyteserin-2a (ILGKLLSTAAGLLSNL.NH 2) is a cationic, a-helical peptide, first isolated from skin secretions of the midwife toad, Alytes obstetricans, which displays relatively weak antimicrobial and haemolytic activities. Increasing the cationicity of alyteserin-2a while maintaining amphipathicity by the substitution Gly 11 ! Lys enhanced the potency against both Gram-negative and Gram-positive bacteria by between fourfold and 16-fold but concomitantly increased cytotoxic activity against human erythrocytes by sixfold (mean concentration of peptide producing 50% cell death; LC 50 = 24 mM). Antimicrobial potency was increased further by the additional substitution Ser 7 !Lys, but the resulting analogue remained cytotoxic to erythrocytes (LC 50 = 38 mM). However, the peptide containing D-lysine at positions 7 and 11 showed high potency against a range of Gram-negative bacteria, including multidrugresistant strains of Acinetobacter baumannii and Stenotrophomonas maltophilia (minimum inhibitory concentration = 8 mM) but appreciably lower haemolytic activity (LC 50 = 185 mM) and cytotoxicity against A549 human alveolar basal epithelial cells (LC 50 = 65 mM). The analogue shows potential for treatment of nosocomial pulmonary infections caused by bacteria that have developed resistance to commonly used antibiotics.

The antimicrobial activities of Circium arvense extracts were evaluated against two human gram positive (Staphylococcus aureus, Micrococcus luteus) and four gram negative pathogen (Escherichia coli, pseudomonas aeruginosa, Enterobacter, Klebsiella pneumoniae). The Methanol extracts of Circium arvense were used to obtain various fractions (X1) n-hexane, (X2) chloroform, (X3) ethyl acetate and (X4) n-butanol. The agar well diffusion assay and agar dilution susceptibility testing were carried out to determine the zone of inhibitions and the minimum inhibitory concentration respectively. Antifungal activity was employed by agar well diffusion method. The Ampicilline, Ofloxacine and Itraconazole were used as standard agents. Almost all fractions exhibited more or less antimicrobial activity. The X2 (Chloroform) fraction was reported as highly active fraction with good antimicrobial activity MIC 0.312 mg/ml against staphylococcus areous. The MBC values of fraction X2 (chloroform) was 2 ti...

Objective: To determine the anticandidal activities of Salvia officinalis L. (S. officinalis) essential oil against Candida albicans (C. albicans) and the inhibitory effects on the adhesion of C. albicans to polymethyl methacrylate (PMMA) resin surface. Methods: Disc diffusion method was first used to test the anticandidal activities of the S. officinalis L. essential oil against the reference strain (ATCC 90028) and 2 clinical strains of C. albicans. Then the minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) were determined by modified membrane method. The adhesion of C. albicans to PMMA resin surface was assessed after immersion with S. officinalis L. essential oil at various concentrations of 1伊MIC, 0.5伊MIC and 0.25伊MIC at room temperature for 30 min. One-way ANOVA was used to compare the Candida cell adhesion with the pretreatment agents and Tukey's test was used for multiple comparisons. Results: S. officinalis L. essential oil exhibited anticandidal activity against all strains of C. albicans with inhibition zone ranging from 40.5 mm to 19.5 mm. The MIC and MLC of the oil were determined as 2.780 g/L against all test strains. According to the effects on C. albicans adhesion to PMMA resin surface, it was found that immersion in the essential oil at concentrations of 1伊MIC (2.780 g/L), 0.5伊MIC (1.390 g/L) and 0.25伊MIC (0.695 g/L) for 30 min significantly reduced the adhesion of all 3 test strains to PMMA resin surface in a dose dependent manner (P<0.05). Conclusions: S. officinalis L. essential oil exhibited anticandidal activities against C. albicans and had inhibitory effects on the adhesion of the cells to PMMA resin surface. With further testing and development, S. officinalis essential oil may be used as an antifungal denture cleanser to prevent candidal adhesion and thus reduce the risk of candida-associated denture stomatitis.

We excised surgically a feline granulomatous lesion and performed histopathological, mycological and molecular examinations. As a result, it was diagnosed as sporotrichosis, which was the second recorded case of a cat so afflicted in Japan. After the operation, we recognized another nodule on the lymph node. Histopathological examination was therefore performed, but no fungi were detected. To prevent recurrence, the cat was administered a antimycotic drug, itraconazole. As a result, no recurrence was found. Excision of the lesion is the treatment of choice for feline sporotrichosis. KEY WORDS: feline, itraconazole, sporotrichosis.

We report two patients with cryptococcal meningitis and combined immunodeficiency with unusual magnetic resonance imaging findings of gadolinium-enhancing white matter lesions, quite different from cryptococcomas and seen prior to anti-fungal treatment. The lesions resembled demyelinating plaques and resolved. In one patient, biopsy of the lesion revealed cryptococci, non-specific inflammatory changes and occasional small perivascular lymphocyte collections, but not demyelination. Leukoencephalopathy, previously rarely observed in Cryptococcal meningitis, was thought to be the sequelae of amphotericin toxicity. Our cases demonstrate cryptococcal meningitis may present with leukoencephalopathy, possibly as an immune response to the organism.

The ability of ozone gas to reduce food spoilage is relatively well documented, but the developmental effects of the gas on food spoilage fungi are not well known. In this study two model aspergilli, Aspergillus nidulans and Aspergillus ochraceus were used to study the effects of ozone on spore germination, sporulation and biomass production. These effects were examined under three levels of ozone; two high level ozone exposures (200 and 300 lmol mol -1 ) and one low level exposure (0.2 lmol mol -1 ). The two species behaved noticeably different to each other. Ozone was more effective in reducing growth from spore inocula than mycelia. No spore production could be detected in A. nidulans exposed to continuous low level O 3 , whereas the same treatment reduced spores produced in A. ochraceus by 94%. Overall the work suggests that ozone exposure is an effective method to prevent spread of fungal spores in a food storage situation.

Bacillomycin Lc, a newantifungal antibiotic of the iturin class, was isolated from a strain of Bacillus subtilis as a set of five congeners. The structure as determined by chemical and spectrometric analyses has been shown to differ from that of bacillomycin L by sequence changes from aspartate-1 to asparagine-1 and from glutamine-5 to glutamate-5. The five congeners differ from each other only in the structure of the aliphatic side chain of the constituent /?-amino acid. The hydrophobicity of the /?-amino acid affects the antifungal activity of the congener, as activity increased in the order of increased congener retention on a reversed-phase HPLCcolumn.

formerly considered to be restricted to tropical and subtropical regions, but several outbreaks of cryptococcosis involving both immunocompetent and immunocompromised individuals have been reported in Canada, the US Pacifi c Northwest, Australia, and South America, indicating its geographic expansion [2,3]. In Brazil, C. neoformans is distributed throughout the country, whereas C. gattii is mainly found in the North and Northeast regions [4]. Due to the increase in the number of immunocompromised individuals over the past several decades, the prevalence of invasive fungal infections has substantially increased worldwide [5]. This has led to high rates of therapeutic and/or prophylactic use of azole derivates and other antifungals, causing selective epidemiological pressure, which may have contributed to the decreased susceptibility to these drugs [6].

The antioxidant, antifungal and antibacterial potentials of volatile oils and oleoresin of Cinnamomum zeylanicum Blume (leaf and bark) were investigated in the present study. The oleoresins have shown excellent activity for the inhibition of primary and secondary oxidation products in mustard oil added at the concentration of 0.02% which were evaluated using peroxide, thiobarbituric acid, p-anisidine and carbonyl values. Moreover, it was further supported by other complementary antioxidant assays such as ferric thiocyanate method in linoleic acid system, reducing power, chelating and scavenging effects on 1,1 0-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals. In antimicrobial investigations, using inverted petriplate and food poison techniques, the leaf and bark volatile oils has been found to be highly effective against all the tested fungi except Aspergillus ochraceus. However, leaf oleoresin has shown inhibition only for Penicillium citrinum whereas bark oleoresin has caused complete mycelial zone inhibition for Aspergillus flavus and A. ochraceus along with Aspergillus niger, Aspergillus terreus, P. citrinum and Penicillium viridicatum at 6 lL. Using agar well diffusion method, leaf volatile oil and oleoresin have shown better results in comparison with bark volatile oil, oleoresin and commercial bactericide, i.e., ampicillin. Gas chromatographic-mass spectroscopy studies on leaf volatile oil and oleoresin resulted in the identification of 19 and 25 components, which accounts for the 99.4% and 97.1%, respectively of the total amount and the major component was eugenol with 87.3% and 87.2%, respectively. The analysis of cinnamon bark volatile oil showed the presence of 13 components accounting for 100% of the total amount. (E)-cinnamaldehyde was found as the major component along with d-cadinene (0.9%), whereas its bark oleoresin showed the presence of 17 components accounting for 92.3% of the total amount. The major components were (E)-cinnamaldehyde (49.9%), along with several other components.

Background One of the main complications of chromoblastomycosis is lymphedema. The purpose of this study was to evaluate the lymphatic system of the limbs of patients with chromoblastomycosis using lymphoscintigraphy. It is a reliable, objective and noninvasive means of supporting the diagnosis of lymphedema. Methods Lymphoscintigraphy was performed in seven patients with chromoblastomycosis, six with lesions in the lower limb and one in the upper limb. Tc-99 m dextran was injected into the interdigital spaces of the upper or lower extremities. The qualitative parameters analyzed were the visibilization of the lymph vessels and the lymph nodes, dermal backflow, and existence of collateral vessels. All patients were treated with the association of itraconazole and cryotherapy with liquid nitrogen. Results Three out of the 14 extremities examined had lymphedema clinically, and the lymphoscintigraphy showed abnormalities in the qualitative parameters; whereas these parameters were normal in the extremities without lymphedema. During the treatment of chromoblastomycosis, a second lymphoscintigraphy exam was performed on 10 limbs and did not show any improvement of the previous lymphoscintigraphic alterations. Conclusions The qualitative lymphoscintigraphy was a reliable method to show the morphology of the lymph vessels and confirm objectively the diagnosis of lymphedema secondary to chromoblastomycosis. The association of oral itraconazol and cryotherapy did not modify the lymphatic alterations in chromoblastomycosis.

A new γ-lactone coumarin, named as excavarin-A, showing antifungal activity was isolated from the leaves of Clausena excavata by bioassay guided fractionation method. The structure was elucidated by spectroscopic data analysis and identified as 7((2E)-4(4,5-dihydro-3-methylene-2-oxo-5-furanyl)-3-methylbut-2-enyloxy) coumarin. Minimum inhibitory concentration (MIC) was determined against fifteen fungal strains pathogenic against plants and human. The least MIC was recorded against the human pathogen, Candida tropicalis and the plant pathogens Rhizoctonia solani and Sclerotinia sclerotiorum. Antifungal activities against the human pathogens, Aspergillus fumigatus and Mucor circinelloides and plant pathogens, Colletotrichum gloeosporioides, Lasiodiplodia theobromae, Fusarium oxysporum and Rhizopus stolonifer were stronger than that of the standard antimicrobials.

Objective: To determine the prevalence and aetiology of dermatophyte infections in relation to social economic factors in primary school children in Kibera. Design: A Cross-sectional descriptive study. Setting: City council sponsored schools namely Olympic, Kibera, Ayany and ...

Although there has been an improved management of Invasive Candidiasis in the last decade, still controversial issues remain, especially in different therapeutic critical care scenarios. We sought to identify the core clinical knowledge and to achieve high agreement recommendations required to care for critically ill adult patients with Invasive Candidiasis for antifungal treatment in special situations and different scenarios. Second Prospective Spanish survey reaching consensus by the Delphi technique, conducted anonymously by electronic e-mail in the first phase to 23 national multidisciplinary experts in invasive fungal infections from five national scientific societies including Intensivists, Anesthesiologists, Microbiologists, Pharmacologists and Infectious disease specialists, answering 30 questions prepared by a coordination group after a strict review of literature in the last five years. The educational objectives spanned four categories, including peritoneal candidiasis, ...

Purpose To study the incidence, clinical presentation, and the response of anti-fungals in cases of fungal endophthalmitis following open globe injury. Methods This is a prospective study of eight cases of post-traumatic fungal endophthalmitis among 110 patients who presented to us with open globe injury between August 2003 and January 2005. Patients with panophthalmitis were eviscerated and rest received intravitreal amphotericin B. Pars plana vitrectomy along with intravitreal miconazole was given in patients with inadequate response to intravitreal amphotericin. Results Two patients had panophthalmitis at the time of presentation and were eviscerated. Six different organisms were isolated from the culture of intraocular specimen of eight patients. The yield of vitreous aspirate was 87.5% and that of aqueous aspirate was 66.6%. Aspergillus sp. and Fusarium sp. were isolated in 62.5% of cases. Minimum inhibitory concentration of amphotericin B and miconazole was less than 3 lg/ml for all organisms except for Paecilomyces lilacinus and Fusarium solani, respectively. In total, 37.5% of patient had final visual acuity of 20/400 or better. Conclusions Fungal endophthalmitis is a relatively rare complication of open globe injury. The final visual outcome after fungal endophthalmitis is dismal. Aspergillus fumigatus was found to be the most virulent organism. All organisms were found to be sensitive to amphotericin B, except P. lilacinus, which was sensitive to miconazole. Repeated intravitreal injection may be required to control the infection. The virulence of the organism and the site of injury are the main determinants of final visual outcome.

Methyl 2- [propanamide-2'-methoxycarbonyl] benzoate, fucosterol, trans-phytol andp-formylphenol were isolated for the first time from a methanolic extract of Jolyna laminarioides. Methyl 2-[propanamide-2'methoxycarbonyll-benzoate exhibited chymotrypsin inhibitory activity and also found to be active against Escherichia coli and Shigella boydii. Fucosterol exhibited antifungal activity against Curvularia lunata, Stachybotrys atra and Microsporum canis. 0 1997 Published by Elsevier Science Ltd

A total of 103 isolates of basidiomycetes, representing 84 species from different Brazilian ecosystems, were evaluated for their antifungal and antibacterial activity in a panel of pathogenic and non-pathogenic microorganisms. Tissue plugs of the fruiting bodies were cultivated in liquid media and the whole culture extracted with ethyl acetate. Crude extracts from Agaricus cf. nigrecentulus, Agrocybe perfecta, Climacodon pulcherrimus, Gloeoporus thelephoroides, Hexagonia hydnoides, Irpex lacteus, Leucoagaricus cf. cinereus, Marasmius cf. bellus, Marasmius sp., Nothopanus hygrophanus, Oudemansiella canarii, Pycnoporus sanguineus, Phellinus sp., and Tyromyces duracinus presented significant activity against one or more of the target microorganisms. Eight isolates were active only against bacteria while three inhibited exclusively the growth of fungi. Two extracts presented wide antimicrobial spectrum and were active against both fungi and bacteria. Differences in the bioactivity of extracts obtained from isolates from the same species were observed.

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The scavenging activity against DPPH (1,1-diphenil-2-picrylhydrazyl) radical and the antifungal effect against chloroform, ethyl acetate and 50% methanolic extracts of Verbena officinalis leaves were investigated. The activity of different fractions of 50% methanolic extract and some isolated compounds were also investigated. The results suggest that 50% methanolic extract and caffeoyl derivatives could potentially be considered as excellent and readily available sources of natural antifungal and antioxidant compounds.

Background: First responders are a high-risk population for occupational stress injuries as they often encounter prolonged stress within their line of work. The aim of this rapid overview of reviews is to summarize existing evidence on interventions for the prevention and management of occupational stress injury (OSI) in first responders. Methods: MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science, and Cochrane Library were searched for systematic reviews examining the impact of prevention, rehabilitation, and resilience-building strategies targeting frontline community safety personnel in February 2019. Pairs of reviewers screened titles and abstracts followed by full-text articles and conducted data abstraction and quality appraisal using the AMSTAR II tool. To ensure a rapid overview process, the search strategy was limited to the last 10 years, quality appraisal of reviews and abstraction of study-level data was completed by one person and verified by another, and the quality of the individual primary studies was not appraised. The findings were summarized descriptively. Results: A total of 14 reviews with 47 unique primary studies were found after screening 1393 records. A majority of studies targeted OSI in police officers (78.7%), followed by firefighters (17%) and correctional officers (4.3%). Of the 47 included primary studies, 24 targeted prevention of OSI (i.e., resilience training, stress management, suicide prevention, and other health promotions) and 23 targeted rehabilitation (i.e., drug therapy, psychotherapy, and other therapies). Prevention strategies including resilience training programs had positive outcomes, while suicide prevention and psychotherapy interventions reported mixed results.

The bis-triazole antifungal fluconazole (FCZ) is used in the systemic treatment of superficial mycoses. The inconvenience of drug interactions and incidence of adverse reactions occurs in approximately 16% of patients, despite several advantages against systemic fungal infections. Because its pharmacokinetics profile is favorable to cutaneous accumulation, it presents a prominent importance in the treatment of superficial mycoses. This study shows FCZ method validation by reversed-phase high-performance liquid chromatography in the linear range of 2 to 32 µg/mL, which suitable for application in biological matrices after topical permeation studies. The method is tested in simulated FCZ alcoholic solution applied to skin extracts after in vitro permeation studies using Franz cells. Recovery shows good results (in the range 75.0% ± 4.1% to 82.0% ± 6.6%) regarding the biological matrices.

The moderate heat treatment of amphotericin B (AmB) in its micellar form (M-AmB) results in superaggregates (H-AmB) that present a substantially lower toxicity and similar activity. The aim of this work was to evaluate the H-AmB behavior after a freeze-drying process. H-AmB and M-AmB micelles were evaluated before and after freeze-drying concerning their physicochemical and biological properties by spectrophotometry and activity/toxicity assay, respectively. Four concentrations of M-AmB and H-AmB were studied aiming to correlate their aggregation state and the respective biological behavior: 50 mg L −1 , 5 mg L −1 , 0.5 mg L −1 , and 0.05 mg L −1. Then, potassium leakage and hemoglobin leakage from red blood cells were used to evaluate the acute and chronic toxicity, respectively. The efficacy of M-AmB and H-AmB formulations was assessed by potassium leakage from Candida albicans and by the broth microdilution method. After heating, in addition to an evident turbidity, a slight blueshift from 327 to 323 nm was also observed at the concentrations of 50 and 5 mg L −1 for H-AmB. Additionally, an increase in the absorbance at 323 nm at the concentration of 0.5 mg L −1 was detected. Concerning the toxicity, H-AmB caused significantly lower hemoglobin leakage than M-AmB. These results were observed for H-AmB before and after freeze-drying. However, there was no difference between H-AmB and M-AmB concerning their activity. Accordingly, the freeze-drying cycle did not show any influence on the behavior of heated formulations, highlighting the suitability of such a method to produce a new AmB product with a long shelf life and with both greater efficiency and less toxicity.

The zoophilic dermatophyte Microsporum canis has cats as natural reservoir, but it is able to infect a wide range of hosts, including humans, where different clinical features of the so-called ringworm dermatophytosis have been described. Human infections are increasingly been reported in Mediterranean countries. A reliable control program against M. canis infection in cats should include an antifungal treatment of both the infected animals and their living environment. In this article, a herbal mixture composed of chemically defined essential oils (EOs) of Litsea cubeba (1%), Illicium verum, Foeniculum vulgare, and Pelargonium graveolens (0.5% each) was formulated and its antifungal activity assessed against M. canis arthrospores which represent the infective environmental stage of M. canis. Single compounds present in higher amounts in the mixture were also separately tested in vitro. Litsea cubeba and P. graveolens EOs were most effective (minimum inhibitory concentration (MIC) 0...

Limited published data are available on dermatophytosis in zoo macropods, despite anecdotal reports of disease occurrence and recurrent mob outbreaks. The aim of this questionnaire study was to analyze data from Australian and international zoos to evaluate estimated disease prevalence in zoos housing macropods, affected macropod species, causative organisms, predisposing factors, clinical presentations, diagnostics, treatments, and disease risk management. Two questionnaires (initial detailed and subsequent brief) were distributed via email to zoo veterinarians, with an estimated response rate of 23%. The overall estimated disease prevalence from responding zoos was 28%, with 73% of responding Australian zoos and 14% of responding non-Australian zoos reporting disease. The first cases of confirmed and suspected dermatophytosis in several macropod species and in association with Trichophyton verrucosum and Trichophyton mentagrophytes var. nodulare are reported, with young red kangaroos (Macropus rufus) appearing predisposed. Diagnosis was most commonly based on fungal culture or presumptively on typical clinical signs of minimally/nonpruritic alopecia, crusting, and scaling distributed most frequently on the tail, pinnae, and hind limbs. Both disease resolution without treatment and resolution after an average of 1to 2 mo of treatment were reported.

Candida auris is an emerging multidrug-resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing.

 Invasive fungal infection (IFI) following liver transplant is associated with significant morbidity and mortality. Antifungal prophylaxis is rational for liver transplant patients at high IFI risk.  In this open-label, noninferiority study, patients were randomized 1:1 to receive intravenous micafungin 100 mg or center-specific standard care (fluconazole, liposomal amphotericin B, or caspofungin) posttransplant. The primary endpoint was clinical success (absence of a proven/probable IFI and no need for additional antifungals) at end of prophylaxis (EOP). Noninferiority (10% margin) of micafungin vs standard care was assessed in the per protocol and full analysis sets. Safety assessments included adverse events and liver and kidney function tests.  The full analysis set comprised 344 patients (172 micafungin; 172 standard care). Mean age was 51.2 years; 48.0% had a Model for End-Stage Liver Disease score ≥20. At EOP (mean treatment duration, 17 days), clinical success was 98.6% for ...

a b s t r a c t 4,5-Dichloro-1,2,3-dithiazolium chloride 2 (Appel salt) reacts with either DMSO, diphenylsulfoxide 11 or methylphenylsulfoxide 12 to give 4-chloro-5H-1,2,3-dithiazol-5-one 1 in excellent yields. The use of catalytic amounts of DMSO (1 mol %) in MeCN in the presence of water (1 equiv) transforms Appel salt 2 into dithiazolone 1 in near quantitative yields (92%). Rational mechanisms are proposed to explain the catalytic nature of these reactions.

Caspofungin has recently been introduced for the treatment of invasive candidiasis, however, there is limited data on its use in endocarditis. We report a 22-year-old male HIV-infected patient on methadone maintenance therapy that developed right-sided Candida albicans endocarditis. Caspofungin treatment and vegetectomy, followed by fluconazole, was successful in the treatment of our patient. We also review all previous cases of Candida endocarditis treated with caspofungin.

Two proteins from the eggshell of Rhodnius prolixus were isolated, characterized and named Rp30 and Rp45 according to their molecular masses. Purified proteins were used to obtain specific antiserum which was later used for immunolocalization. The antiserum against Rp30 and Rp45 detected their presence inside the follicle cells, their secretion and their association with oocyte microvilli. Both proteins are expressed during the final stage of vitellogenesis, preserved during embryogenesis and discarded together with the eggshell. The amino terminals were sequenced and both proteins were further cloned using degenerated primers. The amino acid sequences appear to have a tripartite arrangement with a highly conserved central domain which presents a repetitive motif of valine-proline-valine (VPV) at intervals of 15 amino acid residues. Their amino acid sequence showed no similarity to any known eggshell protein. The expression of these proteins was also investigated; the results demonstrated that this occurred strictly in choriogenic follicles. Antifungal activity against Aspergillus niger was found to be associated with Rp45 but not with Rp30. A. niger exposed to Rp45 protein induced growth inhibition and several morphological changes such as large vacuoles, swollen mitochondria, multi-lamellar structures and a disorganized cell wall as demonstrated by electron microscopy analysis. r

The potential efficacy of four weak acids as preservatives in low-acid intermediate moisture foods was assessed using a glycerol based agar medium. The minimum inhibitory concentrations (MIC, % wt./wt.) of each acid was determined at two pH values (pH 5.0, pH 6.0) and two a w values (0.85, 0.90) for five food spoilage fungi, Eurotium herbariorum, Eurotium rubrum, Aspergillus niger, Aspergillus flavus and Penicillium roqueforti. Sorbic acid, a preservative commonly used to control fungal growth in low-acid intermediate moisture foods, was included as a reference. The MIC values of the four acids were lower at pH 5.0 than pH 6.0 at equivalent a w values, and lower at 0.85 a w than 0.90 a w at equivalent pH values. By comparison with the MIC values of sorbic acid, those of caprylic acid and dehydroacetic acid were generally lower, whereas those for caproic acid were generally higher. No general observation could be made in the case of capric acid. The antifungal activities of all five weak acids appeared related not only to the undissociated form, but also the dissociated form, of each acid.