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.
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.
- Medical mycology : official publication of the International Society for Human and Animal Mycology
- Published almost 7 years ago
Candida glabrata is an infrequent cause of candidemia in Brazilian public hospitals. We investigated putative differences in the epidemiology of candidemia in institutions with different sources of funding. Prospective laboratory-based surveillance of candidemia was conducted in seven private and two public Brazilian tertiary care hospitals. Among 4,363 episodes of bloodstream infection, 300 were caused by Candida spp. (6.9%). Incidence rates were significantly higher in public hospitals, i.e., 2.42 vs. 0.91 episodes per 1,000 admissions (P< 0.01). Patients in private hospitals were older, more likely to be in an intensive care unit and to have been exposed to fluconazole before candidemia. Candida parapsilosis was more frequently recovered as the etiologic agent in public (33% vs. 16%, P< 0.001) hospitals, whereas C. glabrata was more frequently isolated in private hospitals (13% vs. 3%, P < 0.001). Fluconazole resistance among C. glabrata isolates was more frequent in private hospitals (76.5% vs. 20%, P = 0.02). The 30-day mortality was slightly higher among patients in public hospitals (53% vs. 43%, P = 0.10). Candida glabrata is an emerging pathogen in private institutions and in this setting, fluconazole should not be considered as a safe option for primary therapy of candidemia.
Candida famata (also known as Debaryomyces hansenii and Torulopsis candida) is a commensal yeast found in cheese, dairy products and the environment. C. famata accounts for 0.2%-2% of invasive candidiasis. The purpose of this study was to provide an overview of the treatment of C. famata bloodstream infections.
Candidal adhesion has been implicated as the initial step in the pathogenesis of oral candidiasis and cell surface hydrophobicity (CSH) has been implicated in adhesion to mucosal surfaces. Candida dubliniensis is an opportunistic pathogen associated with recurrent oral candidiasis. Chlorhexidine gluconate is by far the commonest antiseptic mouth wash prescribed in dentistry. At dosage intervals the intraoral concentration of this antiseptic fluctuates considerably and reaches sub-therapeutic levels due to the dynamics of the oral cavity. Hence, the organisms undergo only a limited exposure to the antiseptic during treatment. The impact of this antiseptic following such exposure on CSH of C. dubliniensis isolates has not been investigated. Hence, the main objective of this study was to investigate the effect of brief exposure to sub-therapeutic concentrations of chlorhexidine gluconate on the CSH of C. dubliniensis isolates. Twelve oral isolates of C. dubliniensis were briefly exposed to three sub-therapeutic concentrations of 0.005%, 0.0025% and 0.00125% chlorhexidine gluconate for 30 min. Following subsequent removal of the drug, the CSH of the isolates was determined by a biphasic aqueous-hydrocarbon assay. Compared with the controls, exposure to 0.005% and 0.0025% chlorhexidine gluconate suppressed the relative CSH of the total sample tested by 44.49% (P < 0.001) and 21.82% (P < 0.018), respectively, with all isolates being significantly affected. Although exposure to 0.00125% of chlorhexidine gluconate did not elicit a significant suppression on the total sample tested (7.01%; P > 0.05), four isolates of the group were significantly affected. These findings imply that exposure to sub-therapeutic concentrations of chlorhexidine gluconate may suppress CSH of C. dublinienis isolates, thereby reducing its pathogenicity and highlights further the pharmacodynamics of chlorhexidine gluconate.
Establishment of an effective prophylaxis against oral candidiasis by local treatment is essential for immunocompromised patients. The aim of the study is to assess effectiveness and stability of antifungal suspensions for mouthrinses. The assessed suspensions are compounded by one solvent among sterile water, spring water or sodium bicarbonate associated with amphotericin B (Fungizone(®)) or nystatine (Mycostatine(®)). Two others mixes are assessed: Mycostatine(®)-bicarbonate and Mycostatine(®)-Hextril(®)-bicarbonate as well as the two straight antifungal. In vitro activity is tested on five Candida species (C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis) after a five minutes contact between yeasts and the assessed suspension. A galenic study is realized during 3 days. Mixes associating a polyene with sodium bicarbonate have no effectiveness on Candida albicans, others mixes shows intermediate effectiveness (the percentage of yeast growth inhibition lies between 35% and 68%). Effectiveness results of Hextril(®)-based mixes are not explainable because of alcohol in its composition. Spring water-based mixes must be evicted due to microbiologic contaminations after 48hours. Mycostatine(®)-Hextril(®)-bicarbonate mix is not stable during 3 days. All those mouthrinses, poorly effective, excepted on C. glabrata, should be avoided. Straight Mycostatine(®)shows a good antifungal effectiveness excepted on C. krusei and its use should be recommended.
The search for new compounds with antifungal activity is accelerating due to rising yeast and fungal resistance to commonly prescribed drugs. Among the molecules being investigated, plant lectins can be highlighted. The present work shows the potential of six plant lectins which were tested in vitro against yeasts of medical importance, Candida albicans, Candida tropicalis, Candida parapsilosis, Cryptococcus gattii, Cryptococcus neoformans, Malassezia pachydermatis, Rhodotorula sp. and Trichosporon sp. Broth microdilution susceptibility testing was performed in accordance with standard protocols to evaluate antifungal activity. Minimum inhibitory concentration (MIC) was determined at 80 % yeast growth inhibition, whereas the minimum fungicidal concentration (MFC) was evaluated after making the subcultures of each dilution. Only C. parapsilosis growth was inhibited by the lectins tested. Abelmoschus esculentus lectin showed the highest MIC (0.97 μg ml(-1)). Lectins from Canavalia brasiliensis, Mucuna pruriens and Clitoria fairchildiana presented the highest MFC at (3.90 μg ml(-1)). These results encourage further studies with wider yeast strain selections, and open new perspectives for the development of pharmacological molecules.
Candida albicans has a variety of virulence factors, including secreted aspartyl proteases (Saps), which are determinant factors in the pathogenesis of this yeast in immunocompromised patients.
Moxifloxacin (MXF), is a fluoroquinolone drug thought to have some antifungal activity against Candida albicans. The aim of our study was to investigate whether intravitreally and orally administered MXF has an effective penetration into the aqueous and vitreous in an experimental model of C. albicans endophthalmitis.
Comparison of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis adhesive properties and pathogenicity
- International journal of medical microbiology : IJMM
- Published over 6 years ago
Retrospective studies indicate that Candida metapsilosis and Candida orthopsilosis each represents 1-10% of the infections/colonisations attributed to C. parapsilosis by conventional biochemical tests. Little is known on the virulence properties of these fungi and on their role in the establishment/progression of the infection. In this study, the adhesive properties of clinical isolates belonging to the ‘psilosis’ species were assessed in an in vitro model of co-incubation with human buccal epithelial cells (HBECs). Ectophosphatase activity was also measured for all isolates, since the activity of this enzyme has previously been linked to adhesion properties in C. parapsilosis. The results indicate that whilst C. parapsilosis and C. orthopsilosis strains showed similar adhesion abilities, C. metapsilosis isolates displayed a significantly lower ability to adhere to HBECs (P<0.05). No evidence of a correlation between ectophosphatase activity and adhesion was observed, and this finding was also confirmed by phosphatase inhibition experiments. Experimental vaginal candidiasis induced in oestrogen-treated mice with representative isolates of the 3 species indicated that mice infected with C. metapsilosis displayed a reduced vaginal fungal burden, especially in the early stages of the infection. The overall findings confirm that C. orthopsilosis has a comparable behaviour to C. parapsilosis, whilst C. metapsilosis seems to possess a reduced virulence potential.