SCY-078 is an orally bioavailable ß-1,3-glucan synthesis inhibitor (GSI) and the first-in-class of structurally novel triterpine antifungals in clinical development for treating candidemia and invasive candidiasis. In vitro susceptibility by broth micro-dilution, antifungal carry-over, and time-kill dynamics were determined for 3 reference (ATCC) strains (C. albicans 90028, C. parapsilosis 90018, and C. tropicalis 750), a Quality Control (QC) strain (C krusei 6258), and 4 other strains (C. albicans MYA-2732, 64124, 76485 and C.glabrata 90030). Caspofungin (CASP), fluconazole (FLC), and voriconazole (VRC) were comparators. For time-kill experiments, SCY-078 and CASP were evaluated at 0.25, 1, 2, 4, 8, and 16x MIC80, and FLU and VORI were evaluated at 4x MIC80 The time to reach 50%, 90%, and 99.9% growth from starting innoculum was determined. Net change in CFU/mL was used to determine EC50, EC90, and Emax SCY-078 MIC range was between 0.0625 - 1 μg/mL and generally similar to CASP. Antifungal carryover was not observed for SCY-078. SCY-078 was fungicidal against 7 isolates at ≥4x MIC (kill ≥3log10) and achieved a 1.7 log10 reduction in CFUs/mL against C. albicans 90028. CASP behaved similarly against each isolate and achieved a 1.5 log10 reduction in CFUs/mL against C. albicans 90028. Reductions of 50% in CFUs/mL were achieved rapidly (1-2.8 h); fungicidal endpoints were reached at 12.1 - 21.8 h at ≥4x MIC. EC90 was reached at ∼5x MIC at each time point to 24 h. EC50 and EC90 were generally similar (8-24 h). Time-kill behavior of CASP was similar to SCY-078. FLC and VRC were fungistatic. Overall, SCY-078 has primarily fungicidal activity against Candida spp. and behaved comparably to CASP.
This report describes the results of radiological, histological and molecular examination of three farm-reared red-legged partridges (Alectoris rufa) affected by candidiasis.
OBJECTIVE: To discuss the epidemiology of Trichomonas vaginalis (TV) and HIV co-infections, the role of TV in acquisition and transmission of HIV, special treatment considerations for TV among women with HIV and the prevention of TV among HIV-infected persons. DESIGN: Systematic review. DATA SOURCE: Review of literature of EMBASE and PubMed databases from January 1990 to February 2013. Search keywords included TV, HIV co-infections, HIV acquisition, HIV transmission, HIV shedding, TV treatment, HIV and couples studies. REVIEW METHOD: We included studies of any design that contained the selected search words and were published during the specified time frame. We then searched the reference lists of included papers for additional papers and included these when relevant. RESULTS: There is strong evidence that TV increases both transmission and acquisition of HIV among women, and that successful treatment for TV can reduce HIV genital shedding. Single dose metronidazole (MTZ) should no longer be used for HIV+ women with TV given the high rates of asymptomatic bacterial vaginosis co-infections and other factors that may render MTZ less effective in HIV+ women. Prevention of TV among HIV+ persons is similar to among HIV, including promotion of condoms as well as regular screening and prompt treatment. There may be a role for expedited partner treatment for the prevention of repeat infections, but most repeat infections are clinical treatment failures. Diligence in screening and treating TV among both HIV- susceptible and HIV+ persons is an important public health strategy.
BACKGROUND: Oral lichen planus (OLP) is seen frequently in patients with hepatitis C virus (HCV) infection. The aim of this study was to evaluate the occurrence of oral candidiasis, other mucosal lesions, and xerostomia during interferon (IFN) therapy for HCV infection. METHODS: Of 124 patients with HCV-infected liver diseases treated with IFN therapy in our hospital, 14 (mean age 56.00 +/- 12.94 years) who attended to receive administration of IFN once a week were identified and examined for Candida infection and other oral lesions and for the measurement of salivary flow. Serological assays also were carried out. RESULTS: Cultures of Candida from the tongue surfaces were positive in 7 (50.0%) of the 14 patients with HCV infection at least once during IFN therapy. C. albicans was the most common species isolated. The incidence of Candida during treatment with IFN did not increase above that before treatment. Additional oral mucosal lesions were observed in 50.0% (7/14) of patients: OLP in three (21.4%), angular cheilitis in three (21.4%) and recurrent aphthous stomatitis in one (7.1%). OLP occurred in one patient before treatment with IFN, in one during treatment and in one at the end of treatment. 85.7% of the oral lesions were treated with topical steroids. We compared the characteristics of the 7 patients in whom Candida was detected at least once during IFN therapy (group 1) and the 7 patients in whom Candida was not detected during IFN therapy (group 2). The prevalence of oral mucosal lesions (P=0.0075) and incidence of external use of steroids (P=0.0308) in group 1 were significantly higher than in group 2. The average body weight of group 1 decreased significantly compared to group 2 (P=0.0088). Salivary flow decreased in all subjects throughout the course of IFN treatment and returned at 6th months after the end of treatment. In group 1, the level of albumin at the beginning of the 6th month of IFN administration was lower than in group 2 (P=0.0550). According to multivariate analysis, one factor, the presence of oral mucosal lesions, was associated with the detection of Candida. The adjusted odds ratio for the factor was 36.00 (95% confidence interval 2.68-1485.94). CONCLUSION: We should pay more attention to oral candidiasis as well as other oral mucosal lesions, in patients with weight loss during IFN treatment.
BACKGROUND: Incorporation of the solubilizing excipient, sulfobutylether-beta-cyclodextrin (SBECD), in the intravenous (IV) formulation of voriconazole has resulted in the recommendation that this formulation be used with caution in patients with creatinine clearances (Clcr) < 50 mL/min. This study evaluated the safety of IV voriconazole compared with two other IV antifungals not containing SBECD in patients with compromised renal function. METHODS: A total of 128 patients aged 11--93 years who had a baseline Clcr < 50 mL/min between January 1, 2007 and December 31, 2010 were identified from a database of a university-affiliated inpatient healthcare system; of these, 55 patients received caspofungin, 54 patients received fluconazole, and 19 patients received voriconazole. Changes in serum creatinine (Scr) and Clcr levels while on therapy were compared with baseline values and between groups. RESULTS: The groups had similar characteristics apart from the larger proportion of females that received fluconazole. Baseline Scr was higher in those receiving caspofungin, but maximal increases of Scr and decreases in Clcr were greatest for the fluconazole group. Acute kidney injury (AKI), assessed by RIFLE criteria, was more frequent in the fluconazole vs. the caspofungin group (p < 0.01); incidence of AKI in the voriconazole group was not significantly different than found in the other two groups. The infecting organism was a predictor of AKI and formulation with SBECD was not. CONCLUSIONS: Treatment of fungal infections in patients with compromised renal function with an SBECD-containing antifungal agent was not associated with AKI in clinical practice. Since the infecting organism was associated with AKI, decision on which antifungal to use should be determined by susceptibilities to the organism and not the incorporation of SBECD in the IV formulation.
Microbial communities are important to human health. Bacterial vaginosis (BV) is a disease associated with the vagina microbiome. While the causes of BV are unknown, the microbial community in the vagina appears to play a role. We use three different machine-learning techniques to classify microbial communities into BV categories. These three techniques include genetic programming (GP), random forests (RF), and logistic regression (LR). We evaluate the classification accuracy of each of these techniques on two different datasets. We then deconstruct the classification models to identify important features of the microbial community. We found that the classification models produced by the machine learning techniques obtained accuracies above 90% for Nugent score BV and above 80% for Amsel criteria BV. While the classification models identify largely different sets of important features, the shared features often agree with past research.
Development of resistant variants to existing antifungal drugs continues to be the serious problem in Candida albicans-induced fungal pathogenesis, which has a considerable impact on animal and human health. Identification and characterization of newer drugs against C. albicans is, therefore, essential. MMGP1 is a direct cell-penetrating peptide recently identified from marine metagenome, which was found to possess potent antifungal activity against C. albicans.
Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases, and there are controversial reports regarding the diversity of the associated vaginal microbiota. We determined the vaginal microbial community in patients with VVC, bacterial vaginosis (BV), and mixed infection of VVC and BV using Illumina sequencing of 16S rRNA tags. Our results revealed for the first time the highly variable patterns of the vaginal microbiome from VVC patients. In general, the alpha-diversity results of species richness and evenness showed the following order: normal control < VVC only < mixed BV and VVC infection < BV only. The beta-diversity comparison of community structures also showed an intermediate composition of VVC between the control and BV samples. A detailed comparison showed that, although the control and BV communities had typical patterns, the vaginal microbiota of VVC is complex. The mixed BV and VVC infection group showed a unique pattern, with a relatively higher abundance of Lactobacillus than the BV group and higher abundance of Prevotella, Gardnerella, and Atopobium than the normal control. In contrast, the VVC-only group could not be described by any single profile, ranging from a community structure similar to the normal control (predominated with Lactobacillus) to BV-like community structures (abundant with Gardnerella and Atopobium). Treatment of VVC resulted in inconsistent changes of the vaginal microbiota, with four BV/VVC samples recovering to a higher Lactobacillus level, whereas many VVC-only patients did not. These results will be useful for future studies on the role of vaginal microbiota in VVC and related infectious diseases.
The increasing applicability of antifungal treatments, the limited range of available drug classes and the emergence of drug resistance in Candida spp. suggest the need for new treatment options. To explore the applicability of C. albicans photoinactivation, we examined nine structurally different imidazoacridinone derivatives as photosensitizing agents. The most effective derivatives showed a >104-fold reduction of viable cell numbers. The fungicidal action of the three most active compounds was compared at different radiant powers(3.5 to 63 mW/cm2), and this analysis indicated that 7 mW/cm2 was the most efficient. The intracellular accumulation of these compounds in fungal cells correlated with the fungicidal activity of all 9 derivatives. The lack of effect of verapamil, an inhibitor targeting Candida ABC efflux pumps, suggests that these imidazoacridinones are not substrates for ABC transporters. Thus, unlike azoles, a major class of antifungals used against Candida, ABC transporter-mediated resistance is unlikely. Electron paramagnetic resonance (EPR)-spin trapping data suggested that the fungicidal light-induced action of these derivatives might depend on the production of superoxide anion. The highest generation rate of superoxide anion was observed for 1330H, 1610H, and 1611. Singlet oxygen production was also detected upon the irradiation of imidazoacridinone derivatives with UV laser light, with a low to moderate yield, depending on the type of compound. Thus, imidazoacridinone derivatives examined in the present study might act via mixed type I/type II photodynamic mechanism. The presented data indicate lack of direct correlation between the structures of studied imidazoacridinones, cell killing ability, and ROS production. However, we showed for the first time that for imidazoacridinones not only intracellular accumulation is necessary prerequisite of lethal photosensitization of C. albicans, but also localization within particular cellular structures. Our findings present IA derivatives as efficient antifungal photosensitizers with a potential to be used in local treatment of Candida infection.
Vulvovaginal candidiasis (VVC) is an important problem due to Candida spp. The aim of this study was molecular identification, phylogenetic analysis, and evaluation of antifungal susceptibility of non-albicans Candida isolates from VVC.