Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-7 (of 7 Records) |
Query Trace: Vishnu A [original query] |
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Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections.
Ghannoum M , Arendrup MC , Chaturvedi VP , Lockhart SR , McCormick TS , Chaturvedi S , Berkow EL , Juneja D , Tarai B , Azie N , Angulo D , Walsh TJ . Antibiotics (Basel) 2020 9 (9) Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC(50) and MIC(90)) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections. |
Laboratory Analysis of an Outbreak of Candida auris in New York from 2016 to 2018-Impact and Lessons Learned.
Zhu Y , O'Brien B , Leach L , Clark A , Bates M , Adams E , Ostrowsky B , Quinn M , Dufort E , Southwick K , Erazo R , Haley VB , Bucher C , Chaturvedi V , Limberger RJ , Blog D , Lutterloh E , Chaturvedi S . J Clin Microbiol 2019 58 (4) Candida auris is a multidrug-resistant yeast which has emerged in healthcare facilities worldwide, however little is known about identification methods, patient colonization, environmental survival, spread, and drug resistance. Colonization on both biotic (patients) and abiotic (healthcare objects) surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in New York (NY) from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/non-selective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of the internal transcribed spacer (ITS) and D1/D2 regions of the ribosomal gene for C. auris genotyping. Results included: a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates, as well as identification of 277 clinical cases and 350 colonized cases from 151 healthcare facilities including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, c) demonstration of relatively heavier colonization of C. auris in nares compared to the axilla/groin, and d) predominance of the South Asia clade I with intrinsic resistance to fluconazole and elevated minimum inhibitory concentration (MIC) to voriconazole (81%), amphotericin B (61%), 5-FC (3%) and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak. |
Protracted Outbreak of Salmonella Newport Infections Linked to Ground Beef: Possible Role of Dairy Cows - 21 States, 2016-2017.
Marshall KEH , Tewell M , Tecle S , Leeper M , Sinatra J , Kissler B , Fung A , Brown K , Wagner D , Trees E , Hise KB , Chaturvedi V , Schlater LK , Morningstar-Shaw BR , Whitlock L , Holt K , Becker K , Nichols M , Williams IT , Jhung M , Wise ME , Gieraltowski L . MMWR Morb Mortal Wkly Rep 2018 67 (15) 443-446 In January 2017, CDC identified a cluster of Salmonella enterica serotype Newport infections with isolates sharing an indistinguishable pulsed-field gel electrophoresis (PFGE) pattern, JJPX01.0010 (pattern 10), through PulseNet, the national molecular subtyping network for foodborne disease surveillance. This report summarizes the investigation by CDC, state and local health and agriculture departments, and the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS) and discusses the possible role of dairy cows as a reservoir for strains of Salmonella that persistently cause human illness. This investigation combined epidemiologic and whole genome sequencing (WGS) data to link the outbreak to contaminated ground beef; dairy cows were hypothesized to be the ultimate source of Salmonella contamination. |
Laboratory Investigation of <i>Salmonella enterica</i> serovar Poona Outbreak in California: Comparison of Pulsed-Field Gel Electrophoresis (PFGE) and Whole Genome Sequencing (WGS) Results.
Kozyreva VK , Crandall J , Sabol A , Poe A , Zhang P , Concepcion-Acevedo J , Schroeder MN , Wagner D , Higa J , Trees E , Chaturvedi V . PLoS Curr 2016 8 INTRODUCTION: Recently, Salmonella enterica serovar Poona caused a multistate outbreak, with 245 out of 907 cases occurring in California. We report a comparison of pulsed-field gel electrophoresis (PFGE) results with whole genome sequencing (WGS) for genotyping of Salmonella Poona isolates. METHODS: CA Salmonella Poona isolates, collected from July to August 2015, were genotyped by PFGE using XbaI restriction enzyme. WGS was done using Nextera XT library kit with 2x300 bp or 2x250 bp sequencing chemistry on the Illumina MiSeq Sequencer. Reads were mapped to the de novo assembled serovar Poona draft genome (48 contigs, N50= 223,917) from the outbreak using CLCbio GW 8.0.2. The phylogenetic tree was generated based on hqSNPs calling. Genomes were annotated with CGE and PHAST online tools. In silico MLST was performed using the CGE online tool. RESULTS: Human (14) and cucumber (2) Salmonella Poona isolates exhibited 3 possibly related PFGE patterns (JL6X01.0018 [predominant], JL6X01.0375, JL6X01.0778). All isolates that were related by PFGE also clustered together according to the WGS. One isolate with a divergent PFGE pattern (JL6X01.0776) served as an outlier in the phylogenetic analysis and substantially differed from the outbreak clade by WGS. All outbreak isolates were assigned to MLST sequence type 447. The majority of the outbreak-related isolates possessed the same set of Salmonella Pathogenicity Islands with few variations. One outbreak isolate was sequenced and analyzed independently by CDC and CDPH laboratories; there was 0 SNP difference in results. Additional two isolates were sequenced by CDC and the raw data was processed through CDPH and CDC analysis pipelines. Both data analysis pipelines also generated concordant results. Discussion: PFGE and WGS results for the recent CA Salmonella enterica serovar Poona outbreak provided concordant assignment of the isolates to the outbreak cluster. WGS allowed more robust determination of genetic relatedness, provided information regarding MLST-type, pathogenicity genes, and bacteriophage content. WGS data obtained independently at two laboratories showed complete agreement. |
Viable influenza a virus in airborne particles from human coughs
Lindsley WG , Noti JD , Blachere FM , Thewlis RE , Martin SB , Othumpangat S , Noorbakhsh B , Goldsmith WT , Vishnu A , Palmer JE , Clark KE , Beezhold DH . J Occup Environ Hyg 2015 12 (2) 107-13 Patients with influenza release aerosol particles containing the virus into their environment. However, the importance of airborne transmission in the spread of influenza is unclear, in part because of a lack of information about the infectivity of the airborne virus. The purpose of this study was to determine the amount of viable influenza A virus that was expelled by patients in aerosol particles while coughing. Sixty-four symptomatic adult volunteer outpatients were asked to cough 6 times into a cough aerosol collection system. Seventeen of these participants tested positive for influenza A virus by viral plaque assay (VPA) with confirmation by viral replication assay (VRA). Viable influenza A virus was detected in the cough aerosol particles from 7 of these 17 test subjects (41%). Viable influenza A virus was found in the smallest particle size fraction (0.3 mum to 8 mum), with a mean of 142 plaque-forming units (SD 215) expelled during the 6 coughs in particles of this size. These results suggest that a significant proportion of patients with influenza A release small airborne particles containing viable virus into the environment. Although the amounts of influenza A detected in cough aerosol particles during our experiments were relatively low, larger quantities could be expelled by influenza patients during a pandemic when illnesses would be more severe. Our findings support the idea that airborne infectious particles could play an important role in the spread of influenza. |
Is bleach-sedimented smear microscopy an alternative to direct microscopy under programme conditions in India?
Vishnu PH , Bhat P , Bansal A , Satyanarayana S , Alavadi U , Ohri BS , Rao Shrinivas MS , Desikan P , Jaju J , Rao VG , Moonan PK . Public Health Action 2013 3 (1) 23-25 This cross-sectional multi-centric study compared the yield of and potential benefit for detecting smear-positive pulmonary tuberculosis (PTB) by bleach sedimentation (2% sodium-hypochlorite) versus direct microscopy under programme conditions in India. Among 3168 PTB suspects, 684 (21.6%) were detected by bleach sedimentation vs. 625 (19.7%) by direct microscopy, with a proportional overall agreement of 96% ( = 0.88). While 594 patients were smear-positive with both methods, 31 patients detected by direct microscopy were missed and an additional 90 patients were detected by bleach sedimentation. Overall, bleach sedimentation increased the yield of smear-positive TB detection; however; it also increased the time to results. (2013 The Union.) |
Measurements of airborne influenza virus in aerosol particles from human coughs
Lindsley WG , Blachere FM , Thewlis RE , Vishnu A , Davis KA , Cao G , Palmer JE , Clark KE , Fisher MA , Khakoo R , Beezhold DH . PLoS One 2010 5 (11) e15100 Influenza is thought to be communicated from person to person by multiple pathways. However, the relative importance of different routes of influenza transmission is unclear. To better understand the potential for the airborne spread of influenza, we measured the amount and size of aerosol particles containing influenza virus that were produced by coughing. Subjects were recruited from patients presenting at a student health clinic with influenza-like symptoms. Nasopharyngeal swabs were collected from the volunteers and they were asked to cough three times into a spirometer. After each cough, the cough-generated aerosol was collected using a NIOSH two-stage bioaerosol cyclone sampler or an SKC BioSampler. The amount of influenza viral RNA contained in the samplers was analyzed using quantitative real-time reverse-transcription PCR (qPCR) targeting the matrix gene M1. For half of the subjects, viral plaque assays were performed on the nasopharyngeal swabs and cough aerosol samples to determine if viable virus was present. Fifty-eight subjects were tested, of whom 47 were positive for influenza virus by qPCR. Influenza viral RNA was detected in coughs from 38 of these subjects (81%). Thirty-five percent of the influenza RNA was contained in particles >4 microm in aerodynamic diameter, while 23% was in particles 1 to 4 microm and 42% in particles <1 microm. Viable influenza virus was detected in the cough aerosols from 2 of 21 subjects with influenza. These results show that coughing by influenza patients emits aerosol particles containing influenza virus and that much of the viral RNA is contained within particles in the respirable size range. The results support the idea that the airborne route may be a pathway for influenza transmission, especially in the immediate vicinity of an influenza patient. Further research is needed on the viability of airborne influenza viruses and the risk of transmission. |
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