9 results on '"Baker, Stephen"'
Search Results
2. Rapid Detection of Antimicrobial Resistance Genes in Critically Ill Children Using a Custom TaqMan Array Card.
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Clark, John A., Curran, Martin D., Gouliouris, Theodore, Conway Morris, Andrew, Bousfield, Rachel, Navapurkar, Vilas, Kean, Iain R. L., Daubney, Esther, White, Deborah, Baker, Stephen, and Pathan, Nazima
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CRITICALLY ill children ,DRUG resistance in microorganisms ,RAPID diagnostic tests ,RESPIRATORY infections in children ,GENES - Abstract
Bacteria are identified in only 22% of critically ill children with respiratory infections treated with antimicrobial therapy. Once an organism is isolated, antimicrobial susceptibility results (phenotypic testing) can take another day. A rapid diagnostic test identifying antimicrobial resistance (AMR) genes could help clinicians make earlier, informed antimicrobial decisions. Here we aimed to validate a custom AMR gene TaqMan Array Card (AMR-TAC) for the first time and assess its feasibility as a screening tool in critically ill children. An AMR-TAC was developed using a combination of commercial and bespoke targets capable of detecting 23 AMR genes. This was validated using isolates with known phenotypic resistance. The card was then tested on lower respiratory tract and faecal samples obtained from mechanically ventilated children in a single-centre observational study of respiratory infection. There were 82 children with samples available, with a median age of 1.2 years. Major comorbidity was present in 29 (35%) children. A bacterial respiratory pathogen was identified in 13/82 (16%) of children, of which 4/13 (31%) had phenotypic AMR. One AMR gene was detected in 49/82 (60%), and multiple AMR genes were detected in 14/82 (17%) children. Most AMR gene detections were not associated with the identification of phenotypic AMR. AMR genes are commonly detected in samples collected from mechanically ventilated children with suspected respiratory infections. AMR-TAC may have a role as an adjunct test in selected children in whom there is a high suspicion of antimicrobial treatment failure. [ABSTRACT FROM AUTHOR]
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- 2023
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3. What Should We Be Recommending for the Treatment of Enteric Fever?
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Parry, Christopher M, Qamar, Farah N, Rijal, Samita, McCann, Naina, Baker, Stephen, Basnyat, Buddha, Parry, Christopher M [0000-0001-7563-7282], and Apollo - University of Cambridge Repository
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RCTs ,XDR typhoid ,systematic reviews ,enteric fever ,antimicrobial resistance - Abstract
Patients with suspected enteric (typhoid and paratyphoid) fever are predominantly managed as outpatients in endemic regions. Nonspecific clinical presentation, lack of accurate diagnostic tools, and widespread antimicrobial resistance makes management challenging. Resistance has been described for all antimicrobials including chloramphenicol, amoxycillin, trimethoprim-sulfamethoxazole, ciprofloxacin, ceftriaxone, and azithromycin. No significant differences have been demonstrated between these antimicrobials in their ability to treat enteric fever in systematic reviews of randomized controlled trials (RCTs). Antimicrobial choice should be guided by local resistance patterns and national guidance. Extensively drug-resistant typhoid isolates require treatment with azithromycin and/or meropenem. Combining antimicrobials that target intracellular and extracellular typhoid bacteria is a strategy being explored in the Azithromycin and Cefixime in Typhoid Fever (ACT-SA) RCT, in progress in South Asia. Alternative antimicrobials, such as the oral carbapenem, tebipenem, need clinical evaluation. There is a paucity of evidence to guide the antimicrobial management of chronic fecal carriers.
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- 2023
4. The Gut Microbiome of Healthy Vietnamese Adults and Children Is a Major Reservoir for Resistance Genes Against Critical Antimicrobials.
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Pereira-Dias, Joana, Minh, Chau Nguyen Ngoc, Hong, Chau Tran Thi, Nguyen, To Nguyen Thi, Thanh, Tuyen Ha, Zellmer, Caroline, The, Hao Chung, Pike, Lindsay, Higginson, Ellen E, Baker, Stephen, Nguyen Ngoc Minh, Chau, Tran Thi Hong, Chau, Nguyen Thi Nguyen, To, Ha Thanh, Tuyen, and Chung The, Hao
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GUT microbiome ,POPULATION density ,VIETNAMESE people ,SHOTGUN sequencing ,GENES ,OXYGEN consumption - Abstract
Antimicrobials are a key group of therapeutic agents. Given the animal/human population density and high antimicrobial consumption rate in Southeast Asia, the region is a focal area for monitoring antimicrobial resistance (AMR). Hypothesizing that the gastrointestinal tract of healthy individuals in Vietnam is a major source of AMR genes that may be transferred to pathogens, we performed shotgun metagenomic sequencing on fecal samples from 42 healthy Vietnamese people (21 children and 21 adults). We compared their microbiome profiles by age group and determined the composition of AMR genes. An analysis of the taxonomic profiles in the gut microbiome showed a clear differentiation by age, with young children (age <2 years) exhibiting a unique structure in comparison to adults and older children. We identified a total of 132 unique AMR genes, with macrolide, lincosamide, and streptogramin class resistance genes (ermB and lnuC) and tetracycline resistance genes being almost ubiquitous across the study population. Notably, samples from younger children were significantly associated with a greater number of AMR genes than other age groups, including key signature genes associated with AMR pathogens (eg, blaCTX-M, mphA). Our data suggest that the gut microbiome of those living in Vietnam, particularly young children, is a substantial reservoir of AMR genes, which can be transferred to circulating enteric pathogens. Our data support the generation of longitudinal cohort studies of those living in urban and rural areas of developing countries to understand the behavior of these AMR reservoirs and their role in generating multidrug-resistant and extensively drug-resistant pathogens. [ABSTRACT FROM AUTHOR]
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- 2021
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5. Genomic epidemiology, antimicrobial resistance and virulence factors of Enterobacter cloacae complex causing potential community-onset bloodstream infections in a tertiary care hospital of Nepal
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Manandhar, S, Nguyen, Q, Nguyen Thi Nguyen, T, Pham, DT, Rabaa, MA, Dongol, S, Basnyat, B, Dixit, SM, Baker, S, Karkey, A, Baker, Stephen [0000-0003-1308-5755], Karkey, Abhilasha [0000-0002-5179-650X], and Apollo - University of Cambridge Repository
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Vaccine Related ,Infectious Diseases ,Emerging Infectious Diseases ,Biodefense ,Prevention ,3207 Medical Microbiology ,32 Biomedical and Clinical Sciences ,Antimicrobial Resistance ,FOS: Health sciences ,Infection ,3202 Clinical Sciences ,Biotechnology - Abstract
Objectives Community-onset bloodstream infections (BSIs) caused by carbapenemase-producing Enterobacter cloacae complex (ECC) species are increasing internationally. This observation suggests that ECC are emerging pathogens, requiring for detailed understanding on their genomic epidemiology including transmission dynamics and antimicrobial resistance profiles. Patients and methods We performed WGS on 79 Enterobacter spp. isolated from the patients with clinically significant BSIs and admitted to emergency department of a major tertiary hospital in Nepal between April 2016 and October 2017. Results We identified 5 species and 13 STs of ECC. Enterobacter xiangfangensis ST171, one of the globally emerging carbapenem resistant ECC clones with epidemic potential, was the most prevalent (42%). Phylogenetic analysis showed a large (>19 400 SNPs) core genome SNP distance across major STs, which was minimal ( Conclusions Our study highlighted that MDR ECC clones are important pathogens of BSIs in community. Though of low prevalence, carbapenem resistance observed in our ECC isolates raised concern about further community dissemination, underscoring the need for community surveillance to identify MDR ECC clones with epidemic potential.
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- 2022
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6. Mobility of antimicrobial resistance across serovars and disease presentations in non-typhoidal Salmonella from animals and humans in Vietnam
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Samuel Bloomfield, Vu Thuy Duong, Ha Thanh Tuyen, James I. Campbell, Nicholas R. Thomson, Julian Parkhill, Hoang Le Phuc, Tran Thi Hong Chau, Duncan J. Maskell, Gabriel G. Perron, Nguyen Minh Ngoc, Lu Lan Vi, Evelien M. Adriaenssens, Stephen Baker, Alison E. Mather, Parkhill, Julian [0000-0002-7069-5958], Baker, Stephen [0000-0003-1308-5755], and Apollo - University of Cambridge Repository
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plasmids ,Vietnam ,Salmonella ,chromosome arrangements ,Drug Resistance, Bacterial ,Animals ,Humans ,General Medicine ,Typhoid Fever ,Antimicrobial resistance ,Serogroup ,insertion sequences ,Anti-Bacterial Agents - Abstract
Non-typhoidal Salmonella (NTS) is a major cause of bacterial enterocolitis globally but also causes invasive bloodstream infections. Antimicrobial resistance (AMR) hampers the treatment of these infections and understanding how AMR spreads between NTS may help in developing effective strategies. We investigated NTS isolates associated with invasive disease, diarrhoeal disease and asymptomatic carriage in animals and humans from Vietnam. Isolates included multiple serovars and both common and rare phenotypic AMR profiles; long- and short-read sequencing was used to investigate the genetic mechanisms and genomic backgrounds associated with phenotypic AMR profiles. We demonstrate concordance between most AMR genotypes and phenotypes but identified large genotypic diversity in clinically relevant phenotypes and the high mobility potential of AMR genes (ARGs) in this setting. We found that 84 % of ARGs identified were located on plasmids, most commonly those containing IncHI1A_1 and IncHI1B(R27)_1_R27 replicons (33%), and those containing IncHI2_1 and IncHI2A_1 replicons (31%). The vast majority (95%) of ARGS were found within 10 kbp of IS6/IS26 elements, which provide plasmids with a mechanism to exchange ARGs between plasmids and other parts of the genome. Whole genome sequencing with targeted long-read sequencing applied in a One Health context identified a comparatively limited number of insertion sequences and plasmid replicons associated with AMR. Therefore, in the context of NTS from Vietnam and likely for other settings as well, the mechanisms by which ARGs move contribute to a more successful AMR profile than the specific ARGs, facilitating the adaptation of bacteria to different environments or selection pressures.
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- 2022
7. Exploiting genomics to mitigate the public health impact of antimicrobial resistance
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Claire Waddington, Megan E. Carey, Christine J. Boinett, Ellen Higginson, Balaji Veeraraghavan, Stephen Baker, Baker, Stephen [0000-0003-1308-5755], and Apollo - University of Cambridge Repository
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Public health ,Vaccines ,Surveillance ,Review ,Genomics ,Antimicrobial resistance ,Anti-Bacterial Agents ,Anti-Infective Agents ,Drug Resistance, Bacterial ,Genetics ,Molecular Medicine ,Animals ,Humans ,The impact of genomics on precision public health ,Molecular Biology ,Diagnostics ,Genetics (clinical) - Abstract
Antimicrobial resistance (AMR) is a major global public health threat, which has been largely driven by the excessive use of antimicrobials. Control measures are urgently needed to slow the trajectory of AMR but are hampered by an incomplete understanding of the interplay between pathogens, AMR encoding genes, and mobile genetic elements at a microbial level. These factors, combined with the human, animal, and environmental interactions that underlie AMR dissemination at a population level, make for a highly complex landscape. Whole-genome sequencing (WGS) and, more recently, metagenomic analyses have greatly enhanced our understanding of these processes, and these approaches are informing mitigation strategies for how we better understand and control AMR. This review explores how WGS techniques have advanced global, national, and local AMR surveillance, and how this improved understanding is being applied to inform solutions, such as novel diagnostic methods that allow antimicrobial use to be optimised and vaccination strategies for better controlling AMR. We highlight some future opportunities for AMR control informed by genomic sequencing, along with the remaining challenges that must be overcome to fully realise the potential of WGS approaches for international AMR control.
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- 2022
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8. A genomic snapshot of Salmonella enterica serovar Typhi in Colombia
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To Nguyen Thi Nguyen, Duy Pham Thanh, Paula Diaz Guevara, Megan E Carey, Enrique Perez, Thanh Ho Ngoc Dan, Edna Catering Rodríguez, Mailis Maes, Stephen Baker, Carolina Duarte, Isabel Chinen, Lucy Angeline Montaño, Josefina Campos, Maes, Mailis [0000-0002-0266-6557], Thanh, Duy Pham [0000-0001-7029-9210], Duarte, Carolina [0000-0001-7596-8292], Rodriguez, Edna Catering [0000-0001-5537-1923], Montaño, Lucy Angeline [0000-0002-0083-211X], Carey, Megan E. [0000-0002-7797-9080], Campos, Josefina [0000-0003-1409-0441], Perez, Enrique [0000-0002-7730-899X], Apollo - University of Cambridge Repository, Baker, Stephen [0000-0003-1308-5755], and Carey, Megan E [0000-0002-7797-9080]
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Bacterial Diseases ,Epidemiology ,Single Nucleotide Polymorphisms ,RC955-962 ,Salmonella typhi ,Pathology and Laboratory Medicine ,Salmonella Typhi ,Geographical locations ,0302 clinical medicine ,Medical Conditions ,Salmonella ,Arctic medicine. Tropical medicine ,Typhoid ,030212 general & internal medicine ,Clade ,Data Management ,Genetics ,0303 health sciences ,Computer and information sciences ,Genomics ,3. Good health ,Bacterial Pathogens ,Anti-Bacterial Agents ,Phylogenetics ,Infectious Diseases ,Medical Microbiology ,Population Surveillance ,Pathogens ,Public aspects of medicine ,RA1-1270 ,Research Article ,Biology ,Colombia ,Disease Surveillance ,Microbiology ,complex mixtures ,Typhoid fever ,03 medical and health sciences ,Antibiotic resistance ,Enterobacteriaceae ,Microbial Control ,Drug Resistance, Bacterial ,Pulsed-field gel electrophoresis ,medicine ,Evolutionary Systematics ,Typhoid Fever ,Genotyping ,Microbial Pathogens ,030304 developmental biology ,Taxonomy ,Whole genome sequencing ,Pharmacology ,Medicine and health sciences ,Genetic diversity ,Evolutionary Biology ,Bacteria ,Biology and life sciences ,Public Health, Environmental and Occupational Health ,Organisms ,South America ,medicine.disease ,bacterial infections and mycoses ,Antimicrobial Resistance ,People and places - Abstract
Little is known about the genetic diversity of Salmonella enterica serovar Typhi (S. Typhi) circulating in Latin America. It has been observed that typhoid fever is still endemic in this part of the world; however, a lack of standardized blood culture surveillance across Latin American makes estimating the true disease burden problematic. The Colombian National Health Service established a surveillance system for tracking bacterial pathogens, including S. Typhi, in 2006. Here, we characterized 77 representative Colombian S. Typhi isolates collected between 1997 and 2018 using pulse field gel electrophoresis (PFGE; the accepted genotyping method in Latin America) and whole genome sequencing (WGS). We found that the main S. Typhi clades circulating in Colombia were clades 2.5 and 3.5. Notably, the sequenced S. Typhi isolates from Colombia were closely related in a global phylogeny. Consequently, these data suggest that these are endemic clades circulating in Colombia. We found that AMR in S. Typhi in Colombia was uncommon, with a small subset of organisms exhibiting mutations associated with reduced susceptibility to fluoroquinolones. This is the first time that S. Typhi isolated from Colombia have been characterized by WGS, and after comparing these data with those generated using PFGE, we conclude that PFGE is unsuitable for tracking S. Typhi clones and mapping transmission. The genetic diversity of pathogens such as S. Typhi is limited in Latin America and should be targeted for future surveillance studies incorporating WGS., Author summary Salmonella Typhi is the causative agent of typhoid fever, with between 9–13 million cases and 116,800 associated deaths annually. Typhoid fever is still a public health problem mainly in low and middle-income countries (LMICs), including in Latin America, which has a modelled incidence of up to 169 (32–642) cases per 100,000 person-years. Several international studies have aimed to fill data gaps regarding the global distribution and genetic landscape of typhoid; however, in spite of these efforts Latin America is still underrepresented. The globally dominant lineages of S. Typhi (e.g., H58), which often carry multi-drug resistance (MDR) plasmids, decreased fluoroquinolone susceptibility, and now azithromycin resistance, are not detectable by the accepted method (PFGE) used to track outbreaks of typhoid in Latin America. We compared PFGE with whole genome sequence (WGS) and found it correlated poorly, resulting in the over clustering of cases. We additionally found that unlike in most endemic countries, S. Typhi in Colombia are highly antimicrobial susceptible and restricted to a limited number of genotypes that are not as commonly identified in other S. Typhi endemic countries. Our study provides the first enhanced insights into the molecular epidemiology of S. Typhi in Colombia, using WGS data for the first time to investigate the population structure in Colombia and identifying predominant circulating genotypes. Our work demonstrates that routine surveillance with the integration of WGS is necessary not only to improve disease burden estimates, but also to track the national and regional transmission dynamics of S. Typhi.
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- 2021
9. The emergence of azithromycin-resistant Salmonella Typhi in Nepal
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To Nguyen Thi Nguyen, Duy Thanh Pham, Buddha Basnyat, Abhilasha Karkey, Trung Duc Pham, Maia A. Rabaa, Sabina Dongol, Guy E. Thwaites, Abhishek Giri, Quynh Pham Nhu Nguyen, Stephen Baker, Thanh Ngoc Dan Ho, Baker, Stephen [0000-0003-1308-5755], and Apollo - University of Cambridge Repository
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0301 basic medicine ,South asia ,030106 microbiology ,3207 Medical Microbiology ,32 Biomedical and Clinical Sciences ,Biology ,FOS: Health sciences ,Salmonella typhi ,Azithromycin ,complex mixtures ,Typhoid fever ,Microbiology ,Vaccine Related ,03 medical and health sciences ,Rare Diseases ,Phylogenetics ,Clinical Research ,Ampicillin ,Biodefense ,Clinical information ,medicine ,3202 Clinical Sciences ,Transmission (medicine) ,Chloramphenicol ,Prevention ,3 Good Health and Well Being ,medicine.disease ,bacterial infections and mycoses ,Virology ,Ciprofloxacin ,030104 developmental biology ,Infectious Diseases ,Emerging Infectious Diseases ,Antimicrobial Resistance ,Digestive Diseases ,Infection ,medicine.drug - Abstract
Background Typhoid fever remains a significant cause of morbidity and mortality in Asia and Africa. The emergence of azithromycin resistance in South Asia is concerning, as azithromycin is one of the last effective oral drugs for treating typhoid. Objectives To describe the molecular mechanism and phylogenetics of azithromycin-resistant (AzithR) Salmonella Typhi isolates from Patan Hospital, Kathmandu, Nepal. Methods Whole-genome sequences of three AzithR S. Typhi isolates (MIC >256 mg/L) were analysed and compared with a global collection to investigate the azithromycin resistance mechanism and phylogenetic structure. Clinical information is reported for one of the three patients infected with AzithR S. Typhi. Results The three AzithR isolates belonged to the H58 lineage and were genetically identical; they were distantly related to contemporaneous S. Typhi from Nepal and AzithR S. Typhi recently described in Bangladesh. Azithromycin resistance was mediated by a non-synonymous mutation in the acrB gene (R717L). The three AzithR isolates showed reduced susceptibility to ciprofloxacin (double mutation in the gyrA: S83F and D87G), and were susceptible to ampicillin, chloramphenicol and co-trimoxazole. Clinical information from one patient suggested non-response to azithromycin treatment. Conclusions This is the first molecular description of AzithR S. Typhi in Nepal. These organisms showed no phylogenetic link to AzithR S. Typhi in Bangladesh. Our data suggest that increasing use of azithromycin may pose a strong selective pressure driving the emergence of AzithR S. Typhi in South Asia. Further investigations are needed to evaluate treatment responses to azithromycin, predict evolutionary trajectories, and track the transmission of these organisms.
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- 2021
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