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John R. Perfect - One of the best experts on this subject based on the ideXlab platform.
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Candida Glabrata endophthalmitis following penetrating keratoplasty.
Journal of cataract and refractive surgery, 2009Co-Authors: Matthew C. Caldwell, John R. Perfect, Alan N. Carlson, Alan D. ProiaAbstract:We report a case of Candida Glabrata endophthalmitis following penetrating keratoplasty in a 57-year-old man. The infection was thought to be treated successfully with intravitreal amphotericin B but flared 7 months later following cataract extraction and eventually required explantation of the intraocular lens and therapeutic keratoplasty. The literature regarding this rare infection is reviewed. Candida Glabrata, an uncommon ocular pathogen, is being reported with increasing frequency and with a notable predilection for post-keratoplasty eyes. In the 10 reported cases, there is 100% concordance between host and donor tissue cultures. In half the cases, there was a latent period of several months. These infections can be difficult to treat because C Glabrata is often resistant to the antifungal agents commonly used to treat Candida albicans.
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Candida Glabrata fungemia in transplant patients receiving voriconazole after fluconazole
Transplantation, 2005Co-Authors: Barbara D Alexander, Wiley A Schell, Jackie L Miller, Gwynn D Long, John R. PerfectAbstract:The clinical impact of voriconazole resistance in Candida Glabrata is not well described. Five hematopoietic stem cell transplant recipients that developed breakthrough Candida Glabrata bloodstream infections while receiving voriconazole are described and the clinical management and susceptibility profiles of their isolates are reported. All patients were markedly immunosuppressed, and in all cases, voriconazole use was preceded by prolonged fluconazole exposure (median 60 days); median voriconazole exposure prior to candidemia was 48 days. Isolates from 4 patients were shown to be resistant to fluconazole and itraconazole when tested in vitro; these same isolates had MICs to voriconazole and posaconazole > or = 2 microg/ml. Clinical failure to voriconazole may result from deficits in host defense, retained infected foci, and adaptation of the organism to environmental pressures, the specific sequence and mechanisms of which warrant further study. Clinicians must maintain a high index of suspicion for these infections in highly susceptible hosts despite voriconazole therapy, particularly when voriconazole use is preceded by prolonged fluconazole exposure.
Alan D. Proia - One of the best experts on this subject based on the ideXlab platform.
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Candida Glabrata endophthalmitis following penetrating keratoplasty.
Journal of cataract and refractive surgery, 2009Co-Authors: Matthew C. Caldwell, John R. Perfect, Alan N. Carlson, Alan D. ProiaAbstract:We report a case of Candida Glabrata endophthalmitis following penetrating keratoplasty in a 57-year-old man. The infection was thought to be treated successfully with intravitreal amphotericin B but flared 7 months later following cataract extraction and eventually required explantation of the intraocular lens and therapeutic keratoplasty. The literature regarding this rare infection is reviewed. Candida Glabrata, an uncommon ocular pathogen, is being reported with increasing frequency and with a notable predilection for post-keratoplasty eyes. In the 10 reported cases, there is 100% concordance between host and donor tissue cultures. In half the cases, there was a latent period of several months. These infections can be difficult to treat because C Glabrata is often resistant to the antifungal agents commonly used to treat Candida albicans.
Lakshman P. Samaranayake - One of the best experts on this subject based on the ideXlab platform.
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Genotypic, phenotypic and proteomic characterization of Candida Glabrata during sequential fluconazole exposure
Journal of investigative and clinical dentistry, 2011Co-Authors: Y. H. Samaranayake, Becky P. K. Cheung, J. Y. Y. Yau, Kim Wai Yeung, Lakshman P. SamaranayakeAbstract:Aim: Candida Glabrata is a major pathogen in humans known to be intrinsically resistant to fluconazole. However, genotypic, phenotypic, and proteomic changes associated with reduced susceptibility to fluconazole are not properly understood. The aim of this study was to observe specific phenotypic, chromosomal, and proteomic alterations in a Candida Glabrata strain sequentially exposed to fluconazole. Methods: Candida Glabrata was exposed to increased concentrations of fluconazole in RPMI for 55 days. Phenotypic changes were evaluated using standard assays. Molecular/proteomic changes in C. Glabrata were analyzed by contour-clamped homogeneous electric field electrophoresis, reverse transcription–polymerase chain reaction, and mass spectrometry. Results: Candida Glabrata demonstrated increased fluconazole resistance (>256 μg/mL), with extensive cross-resistance to ketoconazole (0.38–3.0 μg), itraconazole (8 to >32 μg), and voriconazole (0.125–1.5 μg). Morphologically dissimilar colonies on RPMI/fluconazole agar demonstrated variable chromosomal profiles compared with the control isolate. Stable chromosomal changes were associated with a significantly higher (P
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Proteomics of drug resistance in Candida Glabrata biofilms
Proteomics, 2010Co-Authors: C. Jayampath Seneviratne, Yu Wang, Lijian Jin, Yoshimitsu Abiko, Lakshman P. SamaranayakeAbstract:Candida Glabrata is a fungal pathogen that causes a variety of mucosal and systemic infections among compromised patient populations with higher mortality rates. Previous studies have shown that biofilm mode of the growth of the fungus is highly resistant to antifungal agents compared with the free-floating or planktonic mode of growth. Therefore, in the present study, we used 2-D DIGE to evaluate the differential proteomic profiles of C. Glabrata under planktonic and biofilm modes of growth. Candida Glabrata biofilms were developed on polystyrene surfaces and age-matched planktonic cultures were obtained in parallel. Initially, biofilm architecture, viability, and antifungal susceptibility were evaluated. Differentially expressed proteins more than 1.5-fold in DIGE analysis were subjected to MS/MS. The transcriptomic regulation of these biomarkers was evaluated by quantitative real-time PCR. Candida Glabrata biofilms were highly resistant to the antifungals and biocides compared with the planktonic mode of growth. Candida Glabrata biofilm proteome when compared with its planktonic proteome showed upregulation of stress response proteins, while glycolysis enzymes were downregulated. Similar trend could be observed at transcriptomic level. In conclusion, C. Glabrata biofilms possess higher amount of stress response proteins, which may potentially contribute to the higher antifungal resistance seen in C. Glabrata biofilms.
Spencer W. Redding - One of the best experts on this subject based on the ideXlab platform.
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In Vitro Interaction of Posaconazole and Caspofungin against Clinical Isolates of Candida Glabrata
Antimicrobial agents and chemotherapy, 2005Co-Authors: Erica R. Oliveira, William R. Kirkpatrick, Brent J. Coco, Thomas F. Patterson, Annette W. Fothergill, Spencer W. ReddingAbstract:Combinations of caspofungin and posaconazole were evaluated by fractional inhibitory concentration index against 119 Candida Glabrata isolates. Synergy was seen in 18% of all isolates and in 4% of fluconazole-resistant isolates at 48 h without evidence of antagonism. This antifungal combination may have utility against this organism.
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Candida Glabrata sepsis secondary to oral colonization in bone marrow transplantation.
Medical mycology, 2004Co-Authors: Spencer W. Redding, Kieren A. Marr, William R. Kirkpatrick, Brent J. Coco, Thomas F. PattersonAbstract:Candida Glabrata has emerged as a common cause of fungal sepsis in bone marrow transplant patients, particularly those receiving fluconazole prophylaxis. Colonization of the lower GI tract and indwelling catheters have been thought to be the primary sources of systemic infection with Candida. We report on a bone marrow transplant patient who developed Candida Glabrata sepsis from pre-existing oral colonization.
David L. Paterson - One of the best experts on this subject based on the ideXlab platform.
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Emergence of novel mutations of caspofungin resistance in Candida Glabrata with prolonged therapy
Pathology, 2010Co-Authors: M.m. Sehu, Hanna Sidjabat, David Ellis, Joseph C. Mccormack, E. Geoffrey Playford, David L. PatersonAbstract:Background Resistance to echinocandin is rare but resistance emerging during therapy has been reported in the literature. In Candida Glabrata , mutations in the FKS1 and FKS2 regions of the glucan synthase complex has been reported. Two clinical isolates of Candida Glabrata from Queensland were noted to be caspofungin resistant after prolonged caspofungin therapy. Aim The aim of this study is to look at the resistance mutation in the Candida Glabrata isolates. Method The caspofungin minimum inhibitory concentration (MIC) for all isolates was confirmed using CLSI M27-A2 methodology. Isogenicity of the isolates was verified by multi-locus sequence typing (MLST). DNA was extracted from the isolates and the regions of interest of the glucan synthase enzyme complex were then sequenced against wild type sequences. Results The raised MIC to caspofungin of the clinical cases was confirmed. Isogenicity was verified with the presence of a persistent unique strain. Two novel mutations in the FKS2 glucan synthase enxyme complex were identified on sequencing, which has not been previously reported. Discussion Candidaemia by non- Candida albicans is increasing. Resistance to caspofungin may lead to treatment failure. It also leaves few alternatives for treatment of life-threatening candidiasis. Emerging resistance to caspofungin in C. Glabrata , especially in cases of prolonged caspofungin exposure, creates the need for increased surveillance and heightened suspicion in the microbiology laboratory as well as in the clinical setting.