9 results on '"Zhang, Sean X."'
Search Results
2. Can Multidrug-Resistant Candida auris Be Reliably Identified in Clinical Microbiology Laboratories?
- Author
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Mizusawa M, Miller H, Green R, Lee R, Durante M, Perkins R, Hewitt C, Simner PJ, Carroll KC, Hayden RT, and Zhang SX
- Subjects
- Candida drug effects, Candidiasis microbiology, Humans, Candida classification, Candida isolation & purification, Candidiasis diagnosis, Drug Resistance, Multiple, Fungal, Microbiological Techniques methods, Mycological Typing Techniques methods, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
- Published
- 2017
- Full Text
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3. The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood.
- Author
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Metzgar D, Frinder MW, Rothman RE, Peterson S, Carroll KC, Zhang SX, Avornu GD, Rounds MA, Carolan HE, Toleno DM, Moore D, Hall TA, Massire C, Richmond GS, Gutierrez JR, Sampath R, Ecker DJ, and Blyn LB
- Subjects
- Algorithms, Anti-Bacterial Agents therapeutic use, DNA Primers, Drug Resistance, Bacterial, Drug Resistance, Fungal, Humans, Limit of Detection, Polymerase Chain Reaction, Reproducibility of Results, Sensitivity and Specificity, Sepsis microbiology, Spectrometry, Mass, Electrospray Ionization, Bacteria isolation & purification, Bacterial Infections blood, Biological Assay methods, Candida isolation & purification, Candidiasis blood, Sepsis blood
- Abstract
Unlabelled: Bloodstream infection (BSI) and sepsis are rising in incidence throughout the developed world. The spread of multi-drug resistant organisms presents increasing challenges to treatment. Surviving BSI is dependent on rapid and accurate identification of causal organisms, and timely application of appropriate antibiotics. Current culture-based methods used to detect and identify agents of BSI are often too slow to impact early therapy and may fail to detect relevant organisms in many positive cases. Existing methods for direct molecular detection of microbial DNA in blood are limited in either sensitivity (likely the result of small sample volumes) or in breadth of coverage, often because the PCR primers and probes used target only a few specific pathogens. There is a clear unmet need for a sensitive molecular assay capable of identifying the diverse bacteria and yeast associated with BSI directly from uncultured whole blood samples. We have developed a method of extracting DNA from larger volumes of whole blood (5 ml per sample), amplifying multiple widely conserved bacterial and fungal genes using a mismatch- and background-tolerant PCR chemistry, and identifying hundreds of diverse organisms from the amplified fragments on the basis of species-specific genetic signatures using electrospray ionization mass spectrometry (PCR/ESI-MS). We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. The assay generated matching results in 80% of culture-positive cases (86% when common contaminants were excluded from the analysis), and twice the total number of positive detections. The described method is capable of providing organism identifications directly from uncultured blood in less than 8 hours., Disclaimer: The IRIDICA BAC BSI Assay is not available in the United States.
- Published
- 2016
- Full Text
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4. Multicenter evaluation of Candida QuickFISH BC for identification of Candida species directly from blood culture bottles.
- Author
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Abdelhamed AM, Zhang SX, Watkins T, Morgan MA, Wu F, Buckner RJ, Fuller DD, Davis TE, Salimnia H, Fairfax MR, Lephart PR, Poulter MD, Regi SB, and Jacobs MR
- Subjects
- Candida genetics, Humans, Sensitivity and Specificity, Blood microbiology, Candida classification, Candida isolation & purification, Candidemia diagnosis, Candidemia microbiology, In Situ Hybridization, Fluorescence methods, Microbiological Techniques methods, Molecular Diagnostic Techniques methods
- Abstract
Candida species are common causes of bloodstream infections (BSI), with high mortality. Four species cause >90% of Candida BSI: C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis. Differentiation of Candida spp. is important because of differences in virulence and antimicrobial susceptibility. Candida QuickFISH BC, a multicolor, qualitative nucleic acid hybridization assay for the identification of C. albicans (green fluorescence), C. glabrata (red fluorescence), and C. parapsilosis (yellow fluorescence), was tested on Bactec and BacT/Alert blood culture bottles which signaled positive on automated blood culture devices and were positive for yeast by Gram stain at seven study sites. The results were compared to conventional identification. A total of 419 yeast-positive blood culture bottles were studied, consisting of 258 clinical samples (89 C. glabrata, 79 C. albicans, 23 C. parapsilosis, 18 C. tropicalis, and 49 other species) and 161 contrived samples inoculated with clinical isolates (40 C. glabrata, 46 C. albicans, 36 C. parapsilosis, 19 C. tropicalis, and 20 other species). A total of 415 samples contained a single fungal species, with C. glabrata (n = 129; 30.8%) being the most common isolate, followed by C. albicans (n = 125; 29.8%), C. parapsilosis (n = 59; 14.1%), C. tropicalis (n = 37; 8.8%), and C. krusei (n = 17; 4.1%). The overall agreement (with range for the three major Candida species) between the two methods was 99.3% (98.3 to 100%), with a sensitivity of 99.7% (98.3 to 100%) and a specificity of 98.0% (99.4 to 100%). This study showed that Candida QuickFISH BC is a rapid and accurate method for identifying C. albicans, C. glabrata, and C. parapsilosis, the three most common Candida species causing BSI, directly from blood culture bottles., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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5. Target enzyme mutations confer differential echinocandin susceptibilities in Candida kefyr.
- Author
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Staab JF, Neofytos D, Rhee P, Jiménez-Ortigosa C, Zhang SX, Perlin DS, and Marr KA
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- Amino Acid Sequence, Antifungal Agents pharmacology, Caspofungin, Drug Resistance, Fungal drug effects, Drug Resistance, Fungal genetics, Fungal Proteins genetics, Glucosyltransferases genetics, Humans, Lipopeptides pharmacology, Micafungin, Microbial Sensitivity Tests methods, Molecular Sequence Data, Sequence Analysis, Protein, Candida drug effects, Candida genetics, Echinocandins pharmacology, Mutation drug effects, Mutation genetics
- Abstract
Candida kefyr is an increasingly reported pathogen in patients with hematologic malignancies. We studied a series of bloodstream isolates that exhibited reduced echinocandin susceptibilities (RES). Clinical and surveillance isolates were tested for susceptibilities to all three echinocandins, and those isolates displaying RES to one or more echinocandins were selected for molecular and biochemical studies. The isolates were analyzed for genetic similarities, and a subset was analyzed for mutations in the echinocandin target gene FKS1 and glucan synthase echinocandin sensitivities using biochemical methods. The molecular typing did not indicate strong genetic relatedness among the isolates except for a series of strains recovered from a single patient. Two unrelated isolates with RES had previously uncharacterized FKS1 mutations: R647G and deletion of amino acid 641 (F641Δ). Biochemical analysis of the semipurified R647G glucan synthase generated differential echinocandin sensitivity (resistance to micafungin only), while the deletion of F641 resulted in a glucan synthase highly insensitive to all three echinocandins. The consecutive isolates from a single patient with RES all harbored the common S645P mutation, which conferred resistance to all three echinocandins. The MIC values paralleled the glucan synthase inhibition kinetic data, although the S645P isolates displayed relatively higher susceptibility to caspofungin (2 μg/ml) than the other two echinocandins (>8 μg/ml). These findings highlight novel and common FKS1 mutations in C. kefyr isolates. The observation of differential susceptibilities to echinocandins may provide important mechanistic insights for echinocandin antifungals., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
- Full Text
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6. Epidemiology of Candida kefyr in patients with hematologic malignancies.
- Author
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Dufresne SF, Marr KA, Sydnor E, Staab JF, Karp JE, Lu K, Zhang SX, Lavallée C, Perl TM, and Neofytos D
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- Adolescent, Adult, Aged, Canada epidemiology, Candida classification, Candida genetics, DNA Fingerprinting, DNA, Fungal genetics, Female, Humans, Incidence, Male, Maryland epidemiology, Middle Aged, Molecular Typing, Mycological Typing Techniques, Retrospective Studies, Seasons, Young Adult, Candida isolation & purification, Candidiasis, Invasive epidemiology, Candidiasis, Invasive microbiology, Hematologic Neoplasms complications
- Abstract
Candida kefyr is an emerging pathogen among patients with hematologic malignancies (HM). We performed a retrospective study at Johns Hopkins Hospital to evaluate the epidemiology of C. kefyr colonization and infection in HM patients between 2004 and 2010. Eighty-three patients were colonized and/or infected with C. kefyr, with 8 (9.6%) having invasive candidiasis (IC). The yearly incidence of C. kefyr colonization and candidemia increased over the study period (P < 0.01), particularly after 2009. In 2010, C. kefyr caused 16.7% of candidemia episodes. The monthly incidence of C. kefyr was higher during the summer throughout the study. In a cohort of patients with acute myelogenic leukemia receiving induction chemotherapy, risks for C. kefyr colonization included the summer season (odds ratio [OR], 3.1; P = 0.03); administration of an azole (OR, 0.06; P < 0.001) or amphotericin B (OR, 0.35; P = 0.05) was protective. Fingerprinting of 16 isolates by repetitive sequence-based PCR showed that all were different genotypes. The epidemiology of C. kefyr candidemia was evaluated in another hospital in Montreal, Canada; data confirmed higher rates of C. kefyr infection in the summer. C. kefyr appears to be increasing in HM patients, with prominent summer seasonality. These findings raise questions about the effect of antifungal agents and health care exposures (e.g., yogurt) on the epidemiology of this yeast., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
- Full Text
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7. False-positive reaction of L-canavanine glycine bromothymol blue medium with Candida famata.
- Author
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Suwantarat N, Watkins T, Lee R, Carroll KC, and Zhang SX
- Subjects
- Bromthymol Blue metabolism, Canavanine metabolism, Child, Preschool, Dermatomycoses diagnosis, Dermatomycoses microbiology, Glycine metabolism, Humans, Male, Scalp Dermatoses diagnosis, Scalp Dermatoses microbiology, Candida classification, Candida isolation & purification, Culture Media chemistry, False Positive Reactions, Microbiological Techniques methods
- Published
- 2014
- Full Text
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8. Candida bracarensis bloodstream infection in an immunocompromised patient.
- Author
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Warren TA, McTaggart L, Richardson SE, and Zhang SX
- Subjects
- Antifungal Agents pharmacology, Bone Marrow Transplantation adverse effects, Candida classification, Candidiasis microbiology, Cluster Analysis, Culture Media chemistry, DNA, Fungal chemistry, DNA, Fungal genetics, DNA, Ribosomal chemistry, DNA, Ribosomal genetics, DNA, Ribosomal Spacer chemistry, DNA, Ribosomal Spacer genetics, Fungemia microbiology, Genes, rRNA, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Mycology methods, Phylogeny, RNA, Fungal genetics, RNA, Ribosomal genetics, Sequence Analysis, DNA, Candida isolation & purification, Candidiasis diagnosis, Fungemia diagnosis, Immunocompromised Host
- Abstract
Candida bracarensis is a recently described Candida species which is phenotypically similar to Candida glabrata. A case of C. bracarensis bloodstream infection in a bone marrow transplant patient is described and confirms this organism as an opportunistic human pathogen. The organism can be distinguished from C. glabrata by its white color on CHROMagar and by DNA sequence analysis using D1/D2 and internal transcribed spacer (ITS) primers.
- Published
- 2010
- Full Text
- View/download PDF
9. Streamlined instrument-free lysis for the detection of Candida auris.
- Author
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Jin, Mei, Trick, Alexander Y., Totten, Marissa, Lee, Pei-wei, Zhang, Sean X., and Wang, Tza-Huei
- Subjects
LYSIS ,HEART beat ,GLASS beads ,POLYMERASE chain reaction ,CANDIDA ,TURNAROUND time - Abstract
The continued spread of Candida auris in healthcare facilities has increased the demand for widely available screening to aid in containment and inform treatment options. Current methods of detection can be unreliable and require bulky and expensive instruments to lyse and identify fungal pathogens. Here, we present a quick, low-cost, instrument-free method for lysis of C. auris suitable for streamlined sample processing with polymerase chain reaction (PCR) detection. Chemical, thermal, and bead beating lysis techniques were evaluated for lysis performance and compatibility with nucleic acid extraction and downstream PCR reactions. Using only 10 s of manual shaking with glass beads, this method demonstrated a limit of detection (LOD) of C. auris at 500 colony forming units per mL, a 20-fold improvement compared to the LOD without manual shaking, and a 60-fold reduction in time compared to common fungal lysis kits, all while maintaining repeatability and reproducibility across multiple users. This work highlights a simple method for increasing sensitivity and reducing turnaround time of PCR-based C. auris detection and exhibits promise for integration into point-of-care platforms towards real-time triage of colonized patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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