Synergistic antifungal activity of statin–azole associations as witnessed by Saccharomyces cerevisiae- and Candida utilis-bioassays and ergosterol quantification

BackgroundFrequent opportunist fungal infections and the resistance to available antifungal drugs promoted the development of new alternatives for treatment, like antifungal drug combinations.AimsThis work aimed to detect the antifungal synergism between statins and azoles by means of an agar-well diffusion bioassay with Saccharomyces cerevisiae ATCC 32051 and Candida utilis Pr_1–2 as test strains.MethodsSynergistic antifungal effects were tested by simultaneously adding a sub inhibitory concentration (SIC) of statin (atorvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin) plus a minimal inhibitory concentration (MIC) of azole (clotrimazole, fluconazole, itraconazole, ketoconazole or miconazole) to yeast-embedded YNB agar plates, and a positive result corresponded to a yeast growth inhibition halo higher than that produced by the MIC of the azole alone. Yeast cell ergosterol quantification by RP-HPLC was used to confirm statin–azole synergism, and ergosterol rescue bioassays were performed for evaluating statin-induced ergosterol synthesis blockage.ResultsGrowth inhibition was significantly increased when clotrimazole, fluconazole, itraconazole, ketoconazole and miconazole were combined with atorvastatin, lovastatin, rosuvastatin and simvastatin. Highest growth inhibition increments were observed on S. cerevisiae (77.5%) and C. utilis (43.2%) with a SIC of simvastatin plus a MIC of miconazole, i.e. 4 + 2.4 μg/ml or 20 + 4.8 μg/ml, respectively. Pravastatin showed almost no significant effects (0–7.6% inhibition increase). Highest interaction ratios between antifungal agents corresponded to simvastatin–miconazole combinations and were indicative of synergism. Synergism was also confirmed by the increased reduction in cellular ergosterol levels (S. cerevisiae, 40% and C. utilis, 22%). Statin-induced ergosterol synthesis blockage was corroborated by means of ergosterol rescue bioassays, pravastatin being the most easily abolished inhibition whilst rosuvastatin being the most ergosterol-refractory.ConclusionsSelected statin–azole combinations might be viable alternatives for the therapeutic management of mycosis at lower administration doses or with a higher efficiency.     

In vitro activity of juglone (5-hydroxy-1,4-naphthoquinone) against both fluconazole-resistant and susceptible Candida isolates

BackgroundThe rise in antifungal resistance and drug class limitations are causing higher morbidity and mortality rates all over the world. This issue highlights the urgent need for new and improved antifungal drugs with a novel target.AimsIn order to evaluate whether juglone can be served as an alternative antifungal to cure drug-resistant Candida infections, we studied the in vitro susceptibility of juglone against fluconazole-susceptible and -resistance Candida isolates, alone and in combination.MethodsAntifungal susceptibility testing was performed according to the CLSI (Clinical and Laboratory Standards Institute) guidelines.ResultsJuglone exhibited the highest minimal inhibitory concentration (MIC) values, followed by fluconazole and nystatin. Voriconazole showed significantly better antifungal activity than juglone, fluconazole, and nystatin, with MIC₅₀ and MIC₉₀ of 0.031 and 0.5 μg/mL. There were significant differences in MICs of fluconazole (p < 0.001) and juglone (p < 0.0003) between Candida albicans and the rest of the species. Combination of juglone with fluconazole revealed insignificant effects against fluconazole-susceptible and -resistant Candida isolates. Juglone increased the antifungal activity of fluconazole; however, no synergism effects were observed for any combination, and only an insignificant effect was found against all tested Candida species.ConclusionsAlthough obtaining new antifungal drugs is a critical point, a completely novel approach should be implemented.     

Antioxidant,Fusarium growth inhibition and Nasutitermes corniger repellent activities of secondary metabolites from Myracrodruon urundeuva heartwood

Myracrodruon urundeuva heartwood is resistant to biodeterioration and lectin purified from heartwood showed antifungal and termiticidal activities. This report deals with antioxidant, antifungal and termite repellent activities of secondary metabolites from M. urundeuva heartwood. Saline (SE, active hemagglutinin preparation) and methanolic (ME, without hemagglutinating activity) extracts contain phenolic compounds, gallic acid, flavonoids, luteolin, cinamic derivatives, proanthocyanidins, hydrolysable tannins, and leucoanthocyanidins. Both SE and ME showed antioxidant activity and were effective in Fusarium growth inhibition. SE was efficient against Fusarium decemcellulare, Fusarium moniliforme, Fusarium oxysporum, and Fusarium solani but it had little effect against Fusarium lateritium. ME practically had no effect on F. decemcellulare and was more active than SE against F. lateritium. SE induced mortality of Nasutitermes corniger (LC₅₀ of 1.81 mg ml^?1 for soldiers and 2.59 mg ml^?1 for workers) and had no repellent activity. ME had no termiticidal activity but was a good repellent. The detected bioactivities point out the possibility of participation of secondary metabolites in the resistance of M. urundeuva heartwood to biodeterioration. Additionally, the results indicate the use of wood residues, as extracts, a source of natural bioactive agents.     

Antifungal peptides homologous to the Penicillium chrysogenum antifungal protein (PAF) are widespread among Fusaria

Putative antifungal peptide encoding genes containing Penicillium chrysogenum antifungal protein (PAF) characteristic amino acid motifs were identified in 15 Fusarium isolates, representing 10 species. Based on the predicted sequences of mature peptides, discrepancy in one, two or three amino acids was observed between them. Phylogenetic investigations revealed that they show high amino acid sequence similarity to PAF and they belong to the group of fungal derived antifungal peptides with PAF-cluster. Ten from the 15 partially purified <10 kDa peptide fraction of Fusarium ferment broths showed antifungal activity. The presence of approximately 6.3 kDa molecular weight peptides was detected in all of the antifungally active ferment broths, and this peptide was isolated and purified from Fusarium polyphilaidicum. The minimal inhibitiory concentrations of F. polyphilaidicum antifungal protein (FPAP) were determined against different filamentous fungi, yeasts and bacteria. Filamentous fungal species were the most susceptible to FPAF, but some yeasts were also slightly sensitive.     

Tinea capitis. Experiencia de 2 años en un hospital de pediatría de Buenos Aires,Argentina

Tinea capitis is an infection caused by dermatophytes of the genera Microsporum and Trichophyton, and constitutes a major health problem in Argentina. The aim of the present study was to find out the incidence of those etiological agents and the therapeutic response in patients attending a High-Complexity Paediatric Hospital within a two-year period. A total of 98 tinea capitis were diagnosed, 13 of which were Celsus kerion. Microsporum canis was isolated in 61.28%. The range of values for minimum inhibitory concentrations were >32, 0,06–4; <0,015–2; <0,015–0.25; 0.13–8; 0.06–128 μg/mL for fluconazole itraconazole, voriconazole, terbinafine, ketoconazole and griseofulvin, respectively.     

Utilidad clínica de la micafungina en el tratamiento de las candidiasis invasoras en el paciente oncohematológico

BackgroundInvasive candidiasis is a severe infection among onco-hematological patients, with an attributable mortality around 40%. Micafungin has shown efficacy in antifungal prophylaxis among hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis.AimsTo assess the role of micafungin in the treatment of invasive candidiasis among onco-hematological patients.MethodsLiterature review.ResultsIn a study on 126 patients with candidemia treated with micafungin, an overall response rate of 83% was reported. A double-blind study of 531 patients with invasive candidiasis comparing micafungin (100 mg/day) versus liposomal amphotericin B (3 mg/kg/day) reported success in 90% of patients in both arms, with a more favorable safety profile with micafungin. Other double blind randomized, phase III study compared two doses of micafungin (100 mg/day and 150 mg/day) with standard doses of caspofungin (70 mg loading dose, then 50 mg/day) in adults with invasive candidiasis. Overall success rate was 74% for micafungin 100 mg/day, 70% for micafungin 150 mg/day, and 71% for caspofungin. A double blind randomized study compared micafungin (2 mg/kg/day) to liposomal amphotericin B (3 mg/kg/day) in the treatment of invasive candidiasis in children with a predominance of infections with non-albicans Candida spp. Overall success rate was similar (73% for micafungin and 76% for liposomal amphotericin B).ConclusionsComparative phase III studies have demonstrated non-inferiority of micafungin compared to standard antifungal agents for invasive candidiasis. Micafungin is safe and effective in the treatment of children and adults with invasive candidiasis. Effectivity in invasive infections caused by non-albicans Candida spp is especially relevant in onco-hematological patients receiving fluconazole prophylaxis.     

Antifungal Activity of Antifungal Drugs,as Well as Drug Combinations Against <Emphasis Type="Italic">Exophiala dermatitidis</Emphasis>

To evaluate the in vitro efficacy of common antifungal drugs, as well as the interactions of caspofungin with voriconazole, amphotericin B, or itraconazole against the pathogenic black yeast Exophiala dermatitidis from China, the minimal inhibitory concentrations (MICs) of terbinafine, voriconazole, itraconazole, amphotericin B, fluconazole, and caspofungin against 16 strains of E. dermatitidis were determined by using CLSI broth microdilution method (M38-A2). The minimal fungicidal concentrations (MFCs) were also determined. Additionally, the interactions of caspofungin with voriconazole, amphotericin B, itraconazole or fluconazole, that of terbinafine with itraconazole, or that of fluconazole with amphotericin B were assessed by using the checkerboard technique. The fractional inhibitory concentration index (FICI) was used to categorize drug interactions as following, synergy, FICI ≤ 0.5; indifference, FICI > 0.5 and ≤4.0; or antagonism, FICI > 4.0. The MIC ranges of terbinafine, voriconazole, itraconazole, amphotericin B, fluconazole, and caspofungin against E. dermatitidis were 0.06–0.125 mg/l, 0.25–1.0 mg/l, 1.0–2.0 mg/l, 1.0–2.0 mg/l, 16–64 mg/l, and 32–64 mg/l, respectively. The in vitro interactions of caspofungin with voriconazole, amphotericin B, and itraconazole showed synergic effect against 10/16(62.5%), 15/16(93.75%), and 16/16(100%) isolates, while that of caspofungin with fluconazole showed indifference. Besides, the interaction of terbinafine with itraconazole as well as that of fluconazole with amphotericin B showed indifference. Terbinafine, voriconazole, itraconazole, and amphotericin B have good activity against E. dermatitidis. The combinations of caspofungin with voriconazole, amphotericin B or itraconazole present synergic activity against E. dermatitidis. These results provide the basis for novel options in treating various E. dermatitidis infections.     

Combined application of botanical formulations and biocontrol agents for the management of Fusarium oxysporum f. sp. cubense (Foc) causing Fusarium wilt in banana

Plant products along with biocontrol agents were tested against Fusarium wilt of banana caused by Fusarium oxysporum f. sp. cubense (Foc). Of the 22 plant species tested, the leaf extract of Datura metel (10%) showed complete inhibition of the mycelial growth of Foc. Two botanical fungicides, Wanis 20 EC and Damet 50 EC along with selected PGPR strains with known biocontrol activity, Pseudomonas fluorescens 1, Pf1 and Bacillus subtilis, TRC 54 were tested individually and in combination for the management of Fusarium wilt under greenhouse and field conditions. Combined application of botanical formulation and biocontrol agents (Wanis 20 EC + Pf1 + TRC 54) reduced the wilt incidence significantly under greenhouse (64%) and field conditions (75%). Reduction in disease incidence was positively correlated with the induction of defense-related enzymes peroxidase (PO) and polyphenol oxidase (PPO). Three antifungal compounds (two glycosides and one ester) in D. metel were separated and identified using TLC, RP-HPLC (Reverse Phase-High Pressure Liquid Chromatography) and mass spectrometry. In this study it is clear that combined application of botanical formulations and biocontrol agents can be very effective in the management of Fusarium wilt of banana.     

A new semi-selective medium for Fusarium graminearum,F. proliferatum,F. subglutinans and F. verticillioides in maize seed

Zea mays L., known also as corn and maize, is the most important crop according to the amount of tonnes produced each year. Fungi cause significant destruction of maize in the field as well as during storage rendering the grain unsuitable for human consumption by decreasing its nutritional value and by producing mycotoxins that are detrimental to both human and animal health. Fusarium species are widely distributed and are amongst the most frequently isolated fungal species by plant pathologists. Due to the fact that the Fusarium species involved in maize ear rot vary in fungicide sensitivity, pathogenicity as well as in their capability to produce mycotoxins, accurate quantification and identification is of paramount significance. Currently no method has been developed to test for Fusarium species in maize seed that has been validated and published by the International Seed Testing Association (ISTA). Malachite green agar 2.5 ppm (MGA 2.5) is a potent selective medium for isolation and enumeration of Fusarium spp. In this study, eight different media compositions, potato dextrose agar (PDA), PDA + malachite green oxalate, corn meal agar, 1/2 PDA + malachite green oxalate, 1% malt agar, carnation leaf agar supplemented with potassium chloride (KCLA), malachite green agar (MGA 2.5) and MGA 2.5 + sterile carnation leaf pieces were compared using four Fusarium species (F. graminearum, F. proliferatum, F. subglutinans and F. verticillioides) and five commonly encountered saprophytic fungi (Aspergillus niger, Penicillium crustosum, P. digitatum, Trichoderma harzianum and Rhizopus stolonifer). The maize kernels were surface disinfected using three concentrations of sodium hypochlorite (0.5%, 1% and 1.5% NaOCl) and for different time intervals (1 min, 3 min, 5 min and 10 min). The effect of black-blue light (365 nm) on sporulation of the fungi was also investigated. Surface disinfection of maize seeds with 1% NaOCl for 5 min provided consistent results. PDA, 1/2 PDA, 1% malt agar and KCLA allowed profuse growth of the Fusarium species as well as saprophytes. Media that contained malachite green oxalate was most inhibitory to the radial colony growth of the saprophytes and the Fusarium species. The Fusarium species growing on these media formed underdeveloped morphological structures, thereby obscuring accurate identification. MGA 2.5 showed better hindering of the saprophytes in some instances. MGA 2.5 amended with sterile carnation leaf pieces was the most satisfactory medium in hindering the growth of the saprophytes while allowing adequate sporulation by the four Fusarium species to permit accurate identification. The media also resulted in higher F. verticillioides and lower saprophytic fungal isolation frequency when compared to the other media tested.     

Amide analogs of antifungal dioxane–triazole derivatives: Synthesis and in vitro activities

A new series of triazole compounds possessing an amide-part were efficiently synthesized and their in vitro antifungal activities were investigated. The amide analogs showed excellent in vitro activity against Candida, Cryptococcus and Aspergillus species. The MICs of compound 23d against C. albicans ATCC24433, C. neoformans TIMM1855 and A. fumigatus ATCC26430 were ?0.008, 0.031 and 0.031 μg/mL, respectively, (MICs of fluconazole: 0.5, >4 and >4 μg/mL; MICs of itraconazole: 0.125, 0.25, 0.25 μg/mL). Furthermore, compound 23d was stable under acidic conditions.     

Primer caso de fungemia asociada a catéter por Candida nivariensis en la Península Ibérica

BackgroundIn recent years the incidence of candidemia caused by non-albicans Candida species has been increasing. Two cryptic species have been described within the Candida glabrata complex, Candida nivariensis and Candida bracarensis, which may be troublesome in laboratory identification and have lower susceptibility to fluconazole.AimsTo describe the first isolation of C. nivariensis in the Iberian Peninsula from a patient suffering from a catheter-related fungemia.Case reportAn 81-year-old man was hospitalized for surgical treatment of an intestinal fistula that was associated to a severe malnutrition. Cultures of the patient's central venous catheter tip and blood yielded white colonies in BD CHROMagar Candida^® medium, which could not be identified by conventional microbiological methods. Although intravenous fluconazole was administered, blood cultures continued being positive 5 days later. The MIC values of the isolate were as follows: 1 μg/ml for amphotericin B, 0.015 μg/ml for anidulafungin, 0.125 μg/ml for caspofungin, 0.015 μg/ml for micafungin, 4 μg/ml for fluconazole, 0.25 μg/ml for itraconazole, 0.25 μg/ml for posaconazole, and 0.03 μg/ml for voriconazole. Antifungal treatment was changed to intravenous caspofungin for 2 weeks. The intestinal fistula was surgically treated. There was no evidence of relapse during the following month, and the patient was discharged. The isolate was identified as C. nivariensis based on DNA sequencing of the ITS regions of rRNA.ConclusionsC. nivariensis should be regarded as an emerging pathogen which requires molecular methods for a definitive identification. Our patient was successfully treated with caspofungin.     

Sensibilidad de aislamientos de Candida albicans de hemocultivos a 3 fármacos: estudio retrospectivo en Rio Grande do Sul,Brasil, 1999 a 2009

BackgroundCandidiasis is one of the most important among recurrent invasive yeast infections in patients, thus antifungal treatment becomes a challenge.AimsThe aim of this study was to evaluate the in vitro activity of clinical Candida albicans isolates from blood cultures to fluconazole, amphotericin B and anidulafungin, in a hospital from Rio Grande do Sul, Brazil.MethodsThe susceptibility of 153 isolates to the 3 drugs mentioned was tested according to Clinical and Laboratory Standars Institute. Minimal inhibitory and fungicidal concentrations (MIC, MFC, respectively) of each drug were determined, as well as the epidemiological cutoff value (ECV).ResultsAll of the isolates were susceptible to anidulafungin, MIC and MFC ≤ 1 μg/ml; however, when compared with ECV, 3% of the isolates exhibited higher values against fluconazole, 96% were susceptible, 3% susceptible dose-dependent, and 1% resistant. Also, it was observed that 21% of the isolates exhibited higher values than ECV. One isolate was resistant to amphotericin B; the other ones, susceptible, based on the MFC; furthermore, 1.5% of the isolates exhibited higher values.ConclusionsC. albicans isolates exhibited more susceptibility to anidulafungin, and 90% of them (MIC₉₀) exhibited the lowest values against amphotericin B. Based on ECV and Pfaller classification, isolates could be resistant to fluconazole, demonstrating the importance of the combination of these parameters.     

Yeasts isolated from nosocomial urinary infections: Antifungal susceptibility and biofilm production

BackgroundUrinary Candida infections in the hospital environment are frequent and need to be better understood.AimsTo compare the results of antifungal susceptibility profiles of yeasts isolated from patients with urinary infections obtained by broth microdilution method (BM) and by disk diffusion (DD), and also evaluate the capacity of these yeasts to form biofilms.MethodsOnly yeasts obtained from pure urine cultures with counts higher than 10⁵ colony-forming units per milliliter, without bacteria development, of symptomatic patients were included. The isolates were identified by classical methods and the antifungal susceptibility tests were performed with the following drugs: amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole and caspofungin. The biofilm studies were carried out in polystyrene microtitration plates.ResultsNinety-five yeasts isolates were analyzed, including 40 Candida albicans, 31 Candida glabrata, 24 Candida tropicalis. In general, the majority of the isolates were susceptible to the tested drugs but some resistance was observed, especially against fluconazole. Great variability in the antifungal susceptibility results was observed with the different tested drugs and a few discrepancies were observed between both methods. We suggest that in case of DD resistance this result should be confirmed by BM, the standard method. C. tropicalis isolates showed high biofilm production (91.7%) compared to C. albicans (82.5%) and C. glabrata (61.3%), with statistical significance (p = 0.0129).ConclusionsCandiduria in critical patients requires major attention and a better control. The different susceptibility results obtained in this study showed the need to identify yeasts up to the species level, especially in patients with urinary tract infection. The development of techniques of antifungal susceptibility tests can help the clinicians in the empiric treatment of candiduria.     

Synergistic fibrinolysis: The combined effects of tissue plasminogen activator and recombinant staphylokinase in vitro

BackgroundMechanisms of fibrin-specificity of tissue plasminogen activator (tPA) and recombinant staphylokinase (STA) are different, therefore we studied in vitro the possibility of the synergy of their combined thrombolytic action.MethodsThrombolytic effects of tPA, STA and their combinations were measured by lysis rate of human plasma clot and side effects were evaluated by decreasing in fibrinogen, plasminogen and α₂-antiplasmin levels in the surrounding plasma at 37 °C in vitro.ResultsSTA and tPA induced dose- and time-dependent clot lysis: 50% lysis in 2 h was obtained with 30 nM tPA and 75 nM STA, respectively. At these concentrations, tPA produced greater degradation of plasma fibrinogen than STA. According to a mathematical analysis of dose–response curves by the isobole method, combinations of tPA and STA caused a considerable synergistic thrombolytic effect. The simultaneous and sequential combinations of tPA (< 4 nM) and STA (< 35 nM) induced a significant fibrin-specific synergistic thrombolysis, which was more pronounced in 2 h at simultaneous combinations than at sequential addition of STA after 30 min of tPA action. Simultaneous combination of 2.5 nM tPA and 15 nM STA showed a maximal 3-fold increase in thrombolytic effect compared to the expected total effect of the individual agents. Sequential combinations caused a lower depletion of plasma proteins compared to simultaneous combinations.ConclusionsThe simultaneous and sequential combinations of tPA and STA possessed synergistic fibrin-specific thrombolytic action on clot lysis in vitro.General significanceThe results show that combined thrombolysis may be more effective and safer than thrombolysis with each activator alone.     

Actividad antifúngica de los enjuagues bucales frente a Candida albicans y Rhodotorula mucilaginosa: un estudio in vitro

BackgroundCandida albicans and Rhodotorula mucilaginosa are yeasts of clinical importance in the oral cavity. In immunocompromised patients they can cause some pathologies that must be controlled with antimicrobials.AimsTo evaluate and compare the antimicrobial efficacy of commercially available mouthrinses against strains of C. albicans and R. mucilaginosa.MethodsThe six mouthwashes studied in vitro were formulated (alone or in combination) with chlorhexidine (CHX) 0.12%, CHX 0.1%, CHX 0.05%, cetylpyridinium chloride (CPC) 0.075%, CPC 0.05%, and essential oils. Ten C. albicans and R. mucilaginosa isolates each were studied. The agar diffusion method (Mueller Hinton II), with incubation at 32 °C was used to evaluate the antifungal activity.ResultsThe results of this study indicate that mouthwashes with CHX 0.1%, CHX 0.12%, CHX 0.05% + CPC 0.05%, CHX 0.12% + CPC 0.05% and CPC 0.075% have an antifungal effect against C. albicans and R. mucilaginosa. CHX 0.1% led to the broadest inhibition zone for C. albicans and R. mucilaginosa (25.65 ± 2.39 mm and 40.05 ± 3.31 mm). Essential oils did not show any antifungal activity. Statistical analysis showed no statistical difference between mouth rinses CHX 0.1%, CHX 0.12% and CHX 0.12% + CPC 0.05% (p = 0.0001) against C. albicans and R. mucilaginosa.ConclusionsMouthwashes with CHX showed higher antifungal activity against C. albicans and R. mucilaginosa than other mouthwashes studied.     

Evaluation of Pseudomonas syringae strain ESC-11 for biocontrol of crown rot and anthracnose of banana

Pseudomonas syringae strain ESC-11 and 250 μg/ml each of thiabendazole (TBZ) and imazalil reduced crown rot of banana caused by Fusarium aff. sacchari by 30–36% and 83–86%, respectively, in laboratory experiments. Four field trials performed in Costa Rica varied in treatment combinations. In field trials 1 and 2, 125 and 250 μg/ml each of TBZ and imazalil + 0.5% or 1% alum (aluminum ammonium sulfate) and ESC-11, and 250 μg/ml each of TBZ and imazalil + 1% alum reduced rot and mold. ESC-11 alone or with 0.5% alum significantly reduced rot and mold in field trial 2. In trial 3, 50 and 100 μg/ml of TBZ alone and with ESC-11 reduced mold. In trial 4, 125 μg/ml each of TBZ and imazalil and ESC-11, and 300 μg/ml each of TBZ and imazalil reduced rot, and 50 and 125 μg/ml each of TBZ and imazalil and ESC-11, and 300 μg/ml each of TBZ and imazalil reduced mold. In three field trials, there was no significant difference among treatments for latex staining. In field trial 2 only, combinations of TBZ, imazalil, and alum with or without ESC-11, reduced anthracnose, caused by Colletotrichum musae. The complex of crown rot fungi, order of treatment application, effect of alum and fungicides on ESC-11, concentration of ESC-11, and level of disease may contribute to the variation in crown rot and anthracnose control by ESC-11. Though ESC-11 alone was not effective in reducing disease, further testing in combination with low rates of fungicide should be done.     

Discovery of highly potent novel antifungal azoles by structure-based rational design

On the basis of the active site of lanosterol 14α-demethylase from Candida albicans (CACYP51), a series of new azoles were designed and synthesized. All the new azoles show excellent in vitro activity against most of the tested pathogenic fungi, which represent a class of promising leads for the development of novel antifungal agents. The MIC₈₀ value of compounds 8c, 8i and 8n against C. albicans is 0.001 μg/mL, indicating that these compounds are more potent than fluconazole, itraconazole and voriconazole. Flexible molecular docking was used to analyze the structure–activity relationships (SARs) of the compounds. The designed compounds interact with CACYP51 through hydrophobic, van der Waals and hydrogen-bonding interactions.     

Exophiala dermatitidis as a cause of central line associated bloodstream infection in an infant: Case report and literature review

BackgroundExophiala dermatitidis is a dematiaceous fungus known to cause superficial, subcutaneous, cutaneous and deep seated infections, and rarely central line associated bloodstream infection (CLABSI). A case of CLABSI due to E. dermatitidis in an infant is described.Case reportClinical and laboratory data were extracted from patient's chart and laboratory records. The isolate was identified as E. dermatitidis by phenotypic characterization and sequencing of the ITS and LSU regions of the ribosomal DNA. Medline search was done to review all cases of CLABSI due to E. dermatitidis. Among the azoles tested, posaconazole (0.06 mg/l), voriconazole (0.03 mg/l) and itraconazole (0.03 mg/l) showed very low MICs when compared to fluconazole (4 mg/l)ConclusionsAs we did not found in the literature any case of CLABSI due to E. dermatitidis in an infant, we report the first one. Sequencing is a mandatory method for accurately identifying this species. Prompt removal of the central line, followed by a treatment with amphotericin B or an azole, seems to be the most effective treatment.     

Study of pharmacodynamic interaction of Phyllanthus emblica extract with clopidogrel and ecosprin in patients with type II diabetes mellitus

BackgroundDiabetes mellitus is associated with oxidative stress which impairs the platelet function. Phyllanthus emblica extract a rich source of vitamin C plays an important role in scavenging free radicals. The effect of vitamin C on platelet aggregation in healthy and coronary artery disease patients has been demonstrated. The present study attempts to study the pharmacodynamic interactions of P. emblica extract with clopidogrel and ecosprin.Materials and methodsThis was a randomized open label crossover study of 10 type II diabetic patients. The dosage schedules were either single dose of 500 mg P. emblica extract or 75 mg clopidogrel or 75 mg ecosprin or 500 mg P. emblica + 75 mg clopidogrel or 500 mg P. emblica + 75 mg ecosprin. After single dose study and washout period, patients received either 500 mg P. emblica extract twice daily or 75 mg clopidogrel or 75 mg ecosprin once daily or combinations for 10 days. Platelet aggregation was measured at baseline and at 4 h of treatment after single and multiple dose study along with recording of bleeding and clotting time.ResultsAfter single and multiple dose administration of the three treatments and with combinations there was statistically significant decrease of platelet aggregation compared to baseline. Further, the mean percent inhibition of platelet aggregation was significant, when compared between single and multiple doses of P. emblica. The bleeding and clotting time was prolonged with single and multiple dose administration of all treatments compared to baseline. All treatments were well tolerated.ConclusionP. emblica extract demonstrated significant antiplatelet activity with both single and multiple dose administration.