The temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for defining intervention, as well ...as planning sustainable prevention strategies.
To identify the phenotypic trends in AMR, 13,833 individual S. Typhi isolates, reported from 1973 to 2018 in 62 publications, were analysed to determine the AMR preponderance over time. Separate analyses of molecular resistance determinants present in over 4,000 isolates reported in 61 publications were also conducted. Multi-drug resistant (MDR) typhoid is in decline in Asia in a setting of high fluoroquinolone resistance while it is on the increase in Africa. Mutations in QRDRs in gyrA (S83F, D87N) and parC (S80I) are the most common mechanisms responsible for fluoroquinolone resistance. Cephalosporin resistant S. Typhi, dubbed extensively drug-resistant (XDR) is a real threat and underscores the urgency in deploying the Vi-conjugate vaccines.
From these observations, it appears that AMR in S. Typhi will continue to emerge leading to treatment failure, changes in antimicrobial policy and further resistance developing in S. Typhi isolates and other Gram-negative bacteria in endemic regions. The deployment of typhoid conjugate vaccines to control the disease in endemic regions may be the best defence.
A typical prokaryote population sequencing study can now consist of hundreds or thousands of isolates. Interrogating these datasets can provide detailed insights into the genetic structure of ...prokaryotic genomes. We introduce Roary, a tool that rapidly builds large-scale pan genomes, identifying the core and accessory genes. Roary makes construction of the pan genome of thousands of prokaryote samples possible on a standard desktop without compromising on the accuracy of results. Using a single CPU Roary can produce a pan genome consisting of 1000 isolates in 4.5 hours using 13 GB of RAM, with further speedups possible using multiple processors.
Roary is implemented in Perl and is freely available under an open source GPLv3 license from http://sanger-pathogens.github.io/Roary
roary@sanger.ac.uk
Supplementary data are available at Bioinformatics online.
Antibiotic resistance in bacteria has emerged as a global challenge over the past 90 years, compromising our ability to effectively treat infections. There has been a dramatic increase in antibiotic ...resistance-associated determinants in bacterial populations, driven by the mobility and infectious nature of such determinants. Bacterial genome flexibility and antibiotic-driven selection are at the root of the problem. Genome evolution and the emergence of highly successful multidrug-resistant clades in different pathogens have made this a global challenge. Here, we describe some of the factors driving the origin, evolution, and spread of the antibiotic resistance genotype.
Antibiotic resistance is a major problem in
serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with ...the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel
Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR
Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the
extended-spectrum β-lactamase, and carrying the
fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of
Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally.
Typhoid fever is a severe disease caused by the Gram-negative bacterium
serovar Typhi. Antibiotic-resistant
Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR)
Typhi clone in Sindh, Pakistan. The XDR
Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in
Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR
Typhi to investigate the phylogenetic relationship between these isolates and a global collection of
Typhi isolates and to identify multiple genes linked to antibiotic resistance. This
Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in
Typhi observed here adds urgency to the need for typhoid prevention measures.
The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate ...individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.
As whole-genome sequencing capacity becomes increasingly decentralized, there is a growing opportunity for collaboration and the sharing of surveillance data within and between countries to inform ...typhoid control policies. This vision requires free, community-driven tools that facilitate access to genomic data for public health on a global scale. Here we present the Pathogenwatch scheme for Salmonella enterica serovar Typhi (S. Typhi), a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are highly concordant with phenotypic susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from >4,300 public genomes available in the application. Pathogenwatch provides an intuitive entry point to monitor of the emergence and spread of S. Typhi high risk clones.
We report a typhoid fever case with a Salmonella enterica serovar Typhi isolate showing extended spectrum β-lactamase (ESBL) production in the Democratic Republic of the Congo. Whole genome ...sequencing revealed that the strain carried a plasmid-mediated CTX-M-15 ESBL gene and did not belong to the dominant H58 Salmonella Typhi clade.
Previous observational work revealed that transient populations in a sustainable building disposed of waste more accurately when compared to patrons in a non-sustainable building. The current study ...uses an experimental design to replicate this observed effect and to investigate whether or not the built environment influences motivational factors to impact behavior. We find support that a building designed and built to communicate an atmosphere of sustainability can influence waste disposal behavior. Participants in the sustainable building used the garbage receptacle significantly less and compensated by tending to select the containers and organics receptacle more, which actually resulted in more errors overall. Our findings suggest that building atmospherics can motivate people to recycle more. However, atmospherics alone do not appear to be sufficient to elicit the desired performance outcome.
Salmonella species commonly causes infection in humans and on occasion leads to serious complications, such as mycotic aneurysms. Here, we present the first case reported of a patient with a mycotic ...aneurysm likely secondary to Salmonella Rissen infection.
The patient presented with 4 weeks of lower back pain, chills and a single episode of diarrhoea 2 months prior during a 14-day trip to Hong Kong and Taiwan. Magnetic resonance imaging revealed an aneurysmal left internal iliac artery with adjacent left iliacus rim-enhancing collection. A stool culture was positive for Salmonella Rissen ST 469 EBG 66 on whole genome sequencing. The patient underwent an emergency bifurcated graft of his internal iliac aneurysm and was successfully treated with appropriate antibiotics.
This case highlights the importance of considering the diagnosis of a mycotic aneurysm in an unusual presentation of back pain with features of infection.
Abstract
Objective
Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO
2
), carbon dioxide generation (VCO
2
), and ...respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients.
Methods
This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled.
Results
We included 4 post-surgery and 6 critical care patients. Of those, 3 critical care patients died. The longest measurement reached to 12 h and 15 min and 50 cycles of repeat measurements were performed. VO
2
of the post-surgery patients were 234 ± 14, 262 ± 27, 212 ± 16, and 192 ± 20 mL/min, and those of critical care patients were 122 ± 20, 189 ± 9, 191 ± 7, 191 ± 24, 212 ± 12, and 135 ± 21 mL/min, respectively. The value of VO
2
was more variable in the post-surgery patients and the range of each patient was 44, 126, 71, and 67, respectively. SOFA scores were higher in non-survivors and there were negative correlations of RQ with SOFA.
Conclusions
We developed an accurate system that enables continuous and repeat measurements of VO
2
, VCO
2
, and RQ. Critical care patients may have less activity in metabolism represented by less variable values of VO
2
and VCO
2
over time as compared to those of post-cardiothoracic surgery patients. Additionally, an alteration of these values may mean a systemic distinction of the metabolism of critically ill patients.
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