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43
result(s) for
"Sheth, Prameet M"
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Carnobacterium inhibens isolated in blood culture of an immunocompromised, metastatic cancer patient: a case report and literature review
2021
Background
Carnobacterium
species are lactic acid-producing Gram-positive bacteria that have been approved by the US Food and Drug Administration and Health Canada for use as a food bio-preservative. The use of live bacteria as a food additive and its potential risk of infections in immunocompromised patients are not well understood.
Case presentation
An 81-year-old male with a history of metastatic prostate cancer on androgen deprivation therapy and chronic steroids presented to our hospital with a 2-week history of productive cough, dyspnea, altered mentation, and fever. Extensive computed tomography imaging revealed multifocal pneumonia without other foci of infection. He was diagnosed with pneumonia and empirically treated with ceftriaxone and vancomycin. Blood cultures from admission later returned positive for
Carnobacterium inhibens
. He achieved clinical recovery with step-down to oral amoxicillin/clavulanic acid for a total 7-day course of antibiotics.
Conclusions
This is the fourth reported case of bacteremia with
Carnobacterium
spp. isolated from humans. This case highlights the need to better understand the pathogenicity and disease spectrum of bacteria used in the food industry for bio-preservation, especially in immunocompromised patients.
Journal Article
Evidence of transmission of Clostridium difficile in asymptomatic patients following admission screening in a tertiary care hospital
2019
Clostridium difficile (CD) is the leading cause of infectious health-care associated diarrhea. However, little is known regarding CD carriage and transmission amongst asymptomatic colonizers. We evaluated carriage, characterized strains and examined epidemiologic linkages in asymptomatic colonized CD patients.
Rectal swabs from asymptomatic patients admitted to the general medicine ward from April 1-June 30 2012 were collected. PCR-confirmed CD colonies were ribotyped and characterized by Modified-Multi Locus Variable Number Tandem Repeat Analysis (MMLVA).
1549-swabs were collected from 474-patients. Overall, 50/474(10.6%) were CD PCR-positive, 24/50 were colonized at admission, while 26/50 were first identified > = 72 hours after admission. Amongst the 50 CD PCR-positive patients, 90% were asymptomatically colonized and 80% of individuals carried toxigenic CD-strains, including ribotype-027 (5/45:11%). MMLVA revealed five-clusters involving 15-patients harboring toxigenic (4/5) and non-toxigenic CD strains (1/5). In two clusters, patients were CD positive on admission while in the other three clusters involving 10 patients, we observed CD transmission from asymptomatically colonized patients to 8 previously CD-negative patients.
We identified increasing rates of colonization during admission to medical wards. MMLVA typing effectively discriminated between strains and suggests that 20% of patients with CD colonization acquired their strain(s) from asymptomatically colonized individuals in hospital.
Journal Article
Molecular Characterization of Klebsiella pneumoniae Carbapenemase (KPC)-Producing Enterobacteriaceae in Ontario, Canada, 2008-2011
by
Sheth, Prameet M.
,
Melano, Roberto G.
,
Tijet, Nathalie
in
Aged
,
Analysis
,
Antibacterial agents
2014
Due to the lack of detailed reports of Klebsiella pneumoniae carbapenemase (KPC)-producing enterobacteria in Ontario, Canada, we perform a molecular characterization of KPC-producing Enterobacteriaceae submitted to the provincial reference laboratory from 2008 to 2011. Susceptibility profiles were accessed by E-test. Molecular types of isolates were determined by pulse-field gel electrophoresis (PFGE) and multilocus sequence typing. Screening of ß-lactamase genes was performed by multiplex PCR and alleles were identified by DNA sequencing. The genetic platform of blaKPC gene was analyzed by PCR. Plasmid replicons were typed using PCR-based typing approach. KPC-plasmids were also evaluated by S1 nuclease-PFGE and Southern blot. Thirty unique clinical isolates (26 Klebsiella pneumoniae, 2 Enterobacter cloacae, 1 Citrobacter freundii and 1 Raoultella ornithinolytica) were identified as blaKPC positive: 4 in 2008, 3 in 2009, 10 in 2010 and 13 in 2011. The majority exhibited resistance to carbapenems, cephalosporins and fluoroquinolones and two isolates were also resistant to colistin. The isolates harbored blaKPC-2 (n = 23) or blaKPC-3 (n = 7). blaTEM-1 (n = 27) was commonly detected and occasionally blaOXA-1 (n = 3) and blaCTX-M-15 (n = 1). As expected, all K. pneumoniae isolates carried blaSHV-11. blaKPC genes were identified on Tn4401a (n = 20) or b (n = 10) isoforms, on plasmids of different sizes belonging to the incompatibility groups IncFIIA (n = 19), IncN (n = 3), IncI2 (n = 3), IncFrep (n = 2) and IncA/C (n = 1). The occurrence of KPC ß-lactamase in Ontario was mainly associated with the spread of the K. pneumoniae clone ST258.
Journal Article
Small-molecule metabolome identifies potential therapeutic targets against COVID-19
2022
Respiratory viruses are transmitted and acquired via the nasal mucosa, and thereby may influence the nasal metabolome composed of biochemical products produced by both host cells and microbes. Studies of the nasal metabolome demonstrate virus-specific changes that sometimes correlate with viral load and disease severity. Here, we evaluate the nasopharyngeal metabolome of COVID-19 infected individuals and report several small molecules that may be used as potential therapeutic targets. Specimens were tested by qRT-PCR with target primers for three viruses: Influenza A (INFA), respiratory syncytial virus (RSV), and SARS-CoV-2, along with unaffected controls. The nasopharyngeal metabolome was characterized using an LC–MS/MS-based screening kit capable of quantifying 141 analytes. A machine learning model identified 28 discriminating analytes and correctly categorized patients with a viral infection with an accuracy of 96% (R
2
= 0.771, Q
2
= 0.72). A second model identified 5 analytes to differentiate COVID19-infected patients from those with INFA or RSV with an accuracy of 85% (R
2
= 0.442, Q
2
= 0.301). Specifically, Lysophosphatidylcholines-a-C18:2 (LysoPCaC18:2) concentration was significantly increased in COVID19 patients (
P
< 0.0001), whereas beta-hydroxybutyric acid, Methionine sulfoxide, succinic acid, and carnosine concentrations were significantly decreased (
P
< 0.0001). This study demonstrates that COVID19 infection results in a unique nasopharyngeal metabolomic signature with carnosine and LysoPCaC18:2 as potential therapeutic targets.
Journal Article
Emergence of a mutation in the nucleocapsid gene of SARS-CoV-2 interferes with PCR detection in Canada
by
R. Barker, Kevin
,
Boissinot, Karel
,
McGeer, Allison J.
in
631/181/757
,
692/699/255
,
Canada - epidemiology
2022
The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) was met with rapid development of robust molecular-based detection assays. Many SARS-CoV-2 molecular tests target multiple genetic regions of the virus to maximize detection and protect against diagnostic escape. Despite the relatively moderate mutational rate of SARS-CoV-2, numerous mutations with known negative impact on diagnostic assays have been identified. In early 2021, we identified four samples positive for SARS-CoV-2 with a nucleocapsid (N) gene drop out on Cepheid Xpert® Xpress SARS-CoV-2 assay. Sequencing revealed a single common mutation in the N gene C29200T. Spatiotemporal analysis showed that the mutation was found in at least six different Canadian provinces from May 2020 until May 2021. Phylogenetic analysis showed that this mutation arose multiple times in Canadian samples and is present in six different variants of interest and of concern. The Cepheid testing platform is commonly used in Canada including in remote regions. As such, the existence of N gene mutation dropouts required further investigation. While commercial SARS-CoV-2 molecular detection assays have contributed immensely to the response effort, many vendors are reluctant to make primer/probe sequences publicly available. Proprietary primer/probe sequences create diagnostic ‘blind spots’ for global SARS-CoV-2 sequence monitoring and limits the ability to detect and track the presence and prevalence of diagnostic escape mutations. We hope that our industry partners will seriously consider making primer/probe sequences available, so that diagnostic escape mutants can be identified promptly and responded to appropriately to maintain diagnostic accuracy.
Journal Article
Staphylococcus aureus nasal carriage is associated with faster symptom resolution following nasal allergen challenge in ragweed-allergic participants: a subset of the Allergic Rhinitis Microbiome Study
2025
In this letter, we report that ragweed-allergic participants with nasal
Staphylococcus aureus
carriage (n = 7) exhibited significantly smaller reductions in Peak Nasal Inspiratory Flow from baseline at 3 h (
P
= 0.013) and 5 h (
P
= 0.008) post–nasal allergen challenge compared to non-carriers (n = 12). There was no significant difference between carriers and non-carriers in the initial response within the first three hours following the challenge (all
P
> 0.05). Carriers also reported significantly lower Total Nasal Symptom Scores (
P
= 0.015) and Total Rhinoconjunctivitis Symptom Scores (
P
= 0.021) at 48 h. These findings suggest that
S. aureus
carriage does not exacerbate allergic responses and may instead be associated with more rapid symptom resolution.
Journal Article
Phylogenomics reveals viral sources, transmission, and potential superinfection in early-stage COVID-19 patients in Ontario, Canada
by
Perez-Patrigeon, Santiago
,
Ayub, Muhammad
,
Hudson, Melissa L.
in
631/208/182
,
631/208/212/2304
,
631/208/514/2254
2021
The emergence and rapid global spread of SARS-CoV-2 demonstrates the importance of infectious disease surveillance, particularly during the early stages. Viral genomes can provide key insights into transmission chains and pathogenicity. Nasopharyngeal swabs were obtained from thirty-two of the first SARS-CoV-2 positive cases (March 18–30) in Kingston Ontario, Canada. Viral genomes were sequenced using Ion Torrent (n = 24) and MinION (n = 27) sequencing platforms. SARS-CoV-2 genomes carried forty-six polymorphic sites including two missense and three synonymous variants in the spike protein gene. The D614G point mutation was the predominate viral strain in our cohort (92.6%). A heterozygous variant (C9994A) was detected by both sequencing platforms but filtered by the ARTIC network bioinformatic pipeline suggesting that heterozygous variants may be underreported in the SARS-CoV-2 literature. Phylogenetic analysis with 87,738 genomes in the GISAID database identified global origins and transmission events including multiple, international introductions as well as community spread. Reported travel history validated viral introduction and transmission inferred by phylogenetic analysis. Molecular epidemiology and evolutionary phylogenetics may complement contact tracing and help reconstruct transmission chains of emerging diseases. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to limit future pandemics.
Journal Article
Correction: Evidence of transmission of Clostridium difficile in asymptomatic patients following admission screening in a tertiary care hospital
2019
[This corrects the article DOI: 10.1371/journal.pone.0207138.].
Journal Article
Evaluating in vivo effectiveness of sotrovimab for the treatment of Omicron subvariant BA.2 versus BA.1: a multicentre, retrospective cohort study
by
Perez-Patrigeon, Santiago
,
Sheth, Prameet M.
,
Lowe, Christopher F.
in
Analysis
,
BA.2 subvariant
,
Biological products
2024
Background
In vitro data suggested reduced neutralizing capacity of sotrovimab, a monoclonal antibody, against Omicron BA.2 subvariant. However, limited in vivo data exist regarding clinical effectiveness of sotrovimab for coronavirus disease 2019 (COVID-19) due to Omicron BA.2.
Methods
A multicentre, retrospective cohort study was conducted at three Canadian academic tertiary centres. Electronic medical records were reviewed for patients ≥ 18 years with mild COVID-19 (sequencing-confirmed Omicron BA.1 or BA.2) treated with sotrovimab between February 1 to April 1, 2022. Thirty-day co-primary outcomes included hospitalization due to moderate or severe COVID-19; all-cause intensive care unit (ICU) admission, and all-cause mortality. Risk differences (BA.2 minus BA.1 group) for co-primary outcomes were adjusted with propensity score matching (e.g., age, sex, vaccination, immunocompromised status).
Results
Eighty-five patients were included (15 BA.2, 70 BA.1) with similar baseline characteristics between groups. Adjusted risk differences were non-statistically significant between groups for 30-day hospitalization (− 14.3%; 95% confidence interval (CI): − 32.6 to 4.0%), ICU admission (− 7.1%; 95%CI: − 20.6 to 6.3%), and mortality (− 7.1%; 95%CI: − 20.6 to 6.3%).
Conclusions
No differences were demonstrated in hospitalization, ICU admission, or mortality rates within 30 days between sotrovimab-treated patients with BA.1 versus BA.2 infection. More real-world data may be helpful to properly assess sotrovimab’s effectiveness against infections due to specific emerging COVID-19 variants.
Journal Article