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Michael A Pfaller - One of the best experts on this subject based on the ideXlab platform.
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antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases
Journal of Clinical Microbiology, 2005Co-Authors: Sandra S Richter, Rudolph P Galask, S A Messer, R J Hollis, Daniel J Diekema, Michael A PfallerAbstract:There are limited data regarding the antifungal susceptibility of yeast causing vulvovaginal candidiasis, since cultures are rarely performed. Susceptibility testing was performed on vaginal yeast isolates collected from January 1998 to March 2001 from 429 patients with suspected vulvovaginal candidiasis. The charts of 84 patients with multiple positive cultures were reviewed. The 593 yeast isolates were Candida albicans (n = 420), Candida glabrata (n = 112), Candida parapsilosis (n = 30), Candida krusei (n = 12), Saccharomyces cerevisiae ( n = 9), Candida tropicalis (n = 8), Candida lusitaniae (n = 1), and Trichosporon sp. (n = 1). Multiple species suggesting mixed infection were isolated from 27 cultures. Resistance to fluconazole and flucytosine was observed infrequently (3.7% and 3.0%); 16.2% of isolates were resistant to itraconazole (MIC ≥ 1 μg/ml). The four imidazoles (econazole, clotrimazole, miconazole, and ketoconazole) were active: 94.3 to 98.5% were susceptible at ≤1 μg/ml. Among different species, elevated fluconazole MICs (≥16 μg/ml) were only observed in C. glabrata (15.2% resistant [R], 51.8% susceptible-dose dependent [S-DD]), C. parapsilosis (3.3% S-DD), S. cerevisiae (11.1% S-DD), and C. krusei (50% S-DD, 41.7% R, considered intrinsically fluconazole resistant). Resistance to itraconazole was observed among C. glabrata (74.1%), C. krusei (58.3%), S. cerevisiae (55.6%), and C. parapsilosis (3.4%). Among 84 patients with recurrent episodes, non-albicans species were more common (42% versus 20%). A ≥4-fold rise in fluconazole MIC was observed in only one patient with C. parapsilosis. These results support the use of azoles for empirical therapy of uncomplicated Candidal vulvovaginitis. Recurrent episodes are more often caused by non-albicans species, for which azole agents are less likely to be effective.
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development of interpretive breakpoints for antifungal susceptibility testing conceptual framework and analysis of in vitro in vivo correlation data for fluconazole itraconazole and Candida infections
Clinical Infectious Diseases, 1997Co-Authors: Michael A Pfaller, Thomas J. Walsh, John N Galgiani, Marilyn S Bartlett, Ana Espinelingroff, Mahmoud A Ghannoum, M Lancaster, F C Odds, Michael G Rinaldi, A L BarryAbstract:The availability of reproducible antifungal susceptibility testing methods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints. In this paper, we have examined the conceptual framework underlying interpretation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respective manufacturers that correlate fluconazole and itraconazole MICs with outcome of Candidal infections. Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinical Laboratory Standards' M27-T broth macrodiltition methodology are proposed: isolates for which MICs are 8 .tg/mL are susceptible to fluconazole, whereas those for which MICs are ,64 itg/mL appear resistant. Isolates for which the MIC of fluconazole is 16-32 tcg/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response when > 100 mg of fluconazole per day is given. These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resistant to fluconazole. Tentative interpretive MIC breakpoints for itraconazole apply only to mucosal Candidal infections and are as follows: susceptible, -_0.125 tcg/mL; S-DD, 0.25 0.5 ttg/mL; and resistant, .- 1.0 iug/mL. These tentative breakpoints are now open for public commentary.
Ilse D. Jacobsen - One of the best experts on this subject based on the ideXlab platform.
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Candida: Platelet Interaction and Platelet Activity in vitro.
Journal of Innate Immunity, 2018Co-Authors: Claudia Eberl, Ilse D. Jacobsen, Magdalena Hagleitner, Cornelia Speth, Hemalata Deshmukh, Christoph G. Ammann, Martin Hermann, Cornelia Lass-flörl, Gunter RambachAbstract:Over the last 2 decades, platelets have been recognized as versatile players of innate immunity. The interaction of platelets with fungal pathogens and subsequent processes may critically influence the clinical outcome of invasive mycoses. Since the role of platelets in Candida infections is poorly characterized and controversially discussed, we studied interactions of human platelets with yeast cells, (pseudo-)hyphae, biofilms and secretory products of human pathogenic Candida species applying platelet rich plasma and a whole blood model. Incubation of Candida with platelets resulted in moderate mutual interaction with some variation between different species. The rate of platelets binding to -Candida (pseudo-) hyphae and Candidal biofilm was comparably low as that to the yeast form. Candida-derived secretory products did not affect platelet activity - neither stimulatory nor inhibitory. The small subset of platelets that bound to Candida morphotypes was consequently activated. However, this did not result in reduced growth or viability of the different Candida species. A whole blood model simulating in vivo conditions confirmed platelet activation in the subpopulation of Candida-bound platelets. Thus, the inability of platelets to efficiently react on Candida presence might favor fungal survival in the blood and contribute to high morbidity of Candida sepsis.
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Candida survival strategies.
Advances in Applied Microbiology, 2015Co-Authors: Melanie Polke, Bernhard Hube, Ilse D. JacobsenAbstract:Abstract Only few Candida species, e.g., Candida albicans , Candida glabrata , Candida dubliniensis , and Candida parapsilosis , are successful colonizers of a human host. Under certain circumstances these species can cause infections ranging from superficial to life-threatening disseminated candidiasis. The success of C. albicans , the most prevalent and best studied Candida species, as both commensal and human pathogen depends on its genetic, biochemical, and morphological flexibility which facilitates adaptation to a wide range of host niches. In addition, formation of biofilms provides additional protection from adverse environmental conditions. Furthermore, in many host niches Candida cells coexist with members of the human microbiome. The resulting fungal–bacterial interactions have a major influence on the success of C. albicans as commensal and also influence disease development and outcome. In this chapter, we review the current knowledge of important survival strategies of Candida spp., focusing on fundamental fitness and virulence traits of C. albicans .
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Galleria mellonella as a model host to study virulence of Candida
Virulence, 2014Co-Authors: Ilse D. JacobsenAbstract:Candida spp. are among the most important human fun-gal pathogens, with infections ranging from relatively benign, superficial manifestation to life-threatening deep-seated candi-diasis and disseminated disease. Different mouse models have been developed to recapitulate the different forms of candidia-sis and murine models are considered to be the gold standard to study pathogenesis and analyze efficacy of antifungal treatment. However, economical, logistical, and ethical considerations limit the use of mammals in infection experiments, especially when the question at hand requires analysis of a large number of fun-gal strains. As an alternative approach, different invertebrate infection models have been developed, including Caenorhabditis elegans, Drosophila melanogaster, and larvae of the wax moth Galleria mellonella as hosts. G. mellonella are inexpensive to pur-chase and do not require specialized facilities for maintenance. The relatively large size of the larvae facilitates easy handling, injection of a defined inoculum, and sampling for downstream analyses. Furthermore, in contrast to other invertebrate hosts, G. mellonella larvae can be maintained at temperatures up to 37 °C, equivalent to the temperature in mammalian hosts. 1 As temperature has been shown to affect expression of Candida virulence traits, this feature is important when assessing viru-lence of Candida strains. 2 In addition, the larval immune system shows functional and structural similarity to the mammalian innate immune system: Pathogens are recognized by pathogen recognition receptors and can be phagocytosed by the insects' hemocytes, the functional equivalent to mammalian neutrophils. Similar to neutrophils, hemocytes use reactive oxygen species and lytic enzymes to eliminate microorganisms. 3 Antimicrobial pep-tides are produced by G. mellonella in response to infection and likely contribute to the host defense, as it has been shown for Candida epithelial infections using mammalian cells. 4,5 Thus, it is not surprising that G. mellonella larvae are used increasingly as a model for Candida infections, for example to determine the virulence of genetically modified C. albicans strains 6-11 and to determine the efficacy of antifungal treatment against both C. albicans and non-albicans Candida species. 12-16 Host mortality after infection with a distinct dose or determi-nation of the LD 50 is commonly used as the primary parameter to assess virulence of microorganisms and to rank the relative virulence of species and strains. Using this approach with sys-temically infected mice, C. albicans and C. tropicalis were found to be highly virulent while other Candida species such as C. gla-brata, C. parapsilosis, and C. krusei induced no mortality, 17 even in immunocompromised mice. 18,19 The high virulence of C. albi-cans in murine models correlates with the clinical situation, in which the majority of Candida infections are caused by C. albi-cans. However, infections with non-albicans Candida species are emerging, including species such as C. glabrata and C. parapsi-losis, which rarely cause lethal infections in mice. In the absence of mortality, fungal burden can be used to compare species and strains.
Antonio Cassone - One of the best experts on this subject based on the ideXlab platform.
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A virosomal vaccine against Candidal vaginitis: Immunogenicity, efficacy and safety profile in animal models
Vaccine, 2012Co-Authors: Flavia De Bernardis, Silvia Arancia, Silvia Sandini, C. Gremion, Mario Amacker, Rinaldo Zurbriggen, Christian Moser, Antonio CassoneAbstract:A novel vaccine (PEV7) consisting of a truncated, recombinant aspartyl proteinase-2 of Candida albicans incorporated into influenza virosomes was studied. This vaccine Candidate generated a potent serum antibody response in mouse and rat following intramuscular immunization. Anti-Sap2 IgG and IgA were also detected in the vaginal fluid of rats following intravaginal or intramuscular plus intravaginal administration. In a rat model of Candidal vaginitis, PEV7 induced significant, long-lasting, likely antibody-mediated, protection following intravaginal route of immunization. PEV7 was also found to be safe in a repeated-dose toxicological study in rats. Overall, these data provide a sound basis to envisage the clinical development of this new Candidate vaccine against Candidal vaginitis. © 2012 Elsevier Ltd.
Sandra S Richter - One of the best experts on this subject based on the ideXlab platform.
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antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases
Journal of Clinical Microbiology, 2005Co-Authors: Sandra S Richter, Rudolph P Galask, S A Messer, R J Hollis, Daniel J Diekema, Michael A PfallerAbstract:There are limited data regarding the antifungal susceptibility of yeast causing vulvovaginal candidiasis, since cultures are rarely performed. Susceptibility testing was performed on vaginal yeast isolates collected from January 1998 to March 2001 from 429 patients with suspected vulvovaginal candidiasis. The charts of 84 patients with multiple positive cultures were reviewed. The 593 yeast isolates were Candida albicans (n = 420), Candida glabrata (n = 112), Candida parapsilosis (n = 30), Candida krusei (n = 12), Saccharomyces cerevisiae ( n = 9), Candida tropicalis (n = 8), Candida lusitaniae (n = 1), and Trichosporon sp. (n = 1). Multiple species suggesting mixed infection were isolated from 27 cultures. Resistance to fluconazole and flucytosine was observed infrequently (3.7% and 3.0%); 16.2% of isolates were resistant to itraconazole (MIC ≥ 1 μg/ml). The four imidazoles (econazole, clotrimazole, miconazole, and ketoconazole) were active: 94.3 to 98.5% were susceptible at ≤1 μg/ml. Among different species, elevated fluconazole MICs (≥16 μg/ml) were only observed in C. glabrata (15.2% resistant [R], 51.8% susceptible-dose dependent [S-DD]), C. parapsilosis (3.3% S-DD), S. cerevisiae (11.1% S-DD), and C. krusei (50% S-DD, 41.7% R, considered intrinsically fluconazole resistant). Resistance to itraconazole was observed among C. glabrata (74.1%), C. krusei (58.3%), S. cerevisiae (55.6%), and C. parapsilosis (3.4%). Among 84 patients with recurrent episodes, non-albicans species were more common (42% versus 20%). A ≥4-fold rise in fluconazole MIC was observed in only one patient with C. parapsilosis. These results support the use of azoles for empirical therapy of uncomplicated Candidal vulvovaginitis. Recurrent episodes are more often caused by non-albicans species, for which azole agents are less likely to be effective.
Flavia De Bernardis - One of the best experts on this subject based on the ideXlab platform.
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A virosomal vaccine against Candidal vaginitis: Immunogenicity, efficacy and safety profile in animal models
Vaccine, 2012Co-Authors: Flavia De Bernardis, Silvia Arancia, Silvia Sandini, C. Gremion, Mario Amacker, Rinaldo Zurbriggen, Christian Moser, Antonio CassoneAbstract:A novel vaccine (PEV7) consisting of a truncated, recombinant aspartyl proteinase-2 of Candida albicans incorporated into influenza virosomes was studied. This vaccine Candidate generated a potent serum antibody response in mouse and rat following intramuscular immunization. Anti-Sap2 IgG and IgA were also detected in the vaginal fluid of rats following intravaginal or intramuscular plus intravaginal administration. In a rat model of Candidal vaginitis, PEV7 induced significant, long-lasting, likely antibody-mediated, protection following intravaginal route of immunization. PEV7 was also found to be safe in a repeated-dose toxicological study in rats. Overall, these data provide a sound basis to envisage the clinical development of this new Candidate vaccine against Candidal vaginitis. © 2012 Elsevier Ltd.
