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In silico evaluation and exploration of antibiotic tuberculosis treatment regimens

Overview of attention for article published in BMC Systems Biology, November 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#17 of 1,107)
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • High Attention Score compared to outputs of the same age and source (95th percentile)

Mentioned by

news
3 news outlets
twitter
3 tweeters

Citations

dimensions_citation
26 Dimensions

Readers on

mendeley
43 Mendeley
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Title
In silico evaluation and exploration of antibiotic tuberculosis treatment regimens
Published in
BMC Systems Biology, November 2015
DOI 10.1186/s12918-015-0221-8
Pubmed ID
Authors

Elsje Pienaar, Véronique Dartois, Jennifer J. Linderman, Denise E. Kirschner

Abstract

Improvement in tuberculosis treatment regimens requires selection of antibiotics and dosing schedules from a large design space of possibilities. Incomplete knowledge of antibiotic and host immune dynamics in tuberculosis granulomas impacts clinical trial design and success, and variations among clinical trials hamper side-by-side comparison of regimens. Our objective is to systematically evaluate the efficacy of isoniazid and rifampin regimens, and identify modifications to these antibiotics that improve treatment outcomes. We pair a spatio-temporal computational model of host immunity with pharmacokinetic and pharmacodynamic data on isoniazid and rifampin. The model is calibrated to plasma pharmacokinetic and granuloma bacterial load data from non-human primate models of tuberculosis and to tissue and granuloma measurements of isoniazid and rifampin in rabbit granulomas. We predict the efficacy of regimens containing different doses and frequencies of isoniazid and rifampin. We predict impacts of pharmacokinetic/pharmacodynamic modifications on antibiotic efficacy. We demonstrate that suboptimal antibiotic concentrations within granulomas lead to poor performance of intermittent regimens compared to daily regimens. Improvements from dose and frequency changes are limited by inherent antibiotic properties, and we propose that changes in intracellular accumulation ratios and antimicrobial activity would lead to the most significant improvements in treatment outcomes. Results suggest that an increased risk of drug resistance in fully intermittent as compared to daily regimens arises from higher bacterial population levels early during treatment. Our systems pharmacology approach complements efforts to accelerate tuberculosis therapeutic development.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Russia 1 2%
Unknown 41 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 21%
Student > Ph. D. Student 6 14%
Student > Doctoral Student 5 12%
Other 4 9%
Student > Master 4 9%
Other 8 19%
Unknown 7 16%
Readers by discipline Count As %
Medicine and Dentistry 7 16%
Biochemistry, Genetics and Molecular Biology 4 9%
Chemistry 4 9%
Engineering 4 9%
Agricultural and Biological Sciences 4 9%
Other 14 33%
Unknown 6 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 24. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 July 2016.
All research outputs
#862,842
of 15,916,297 outputs
Outputs from BMC Systems Biology
#17
of 1,107 outputs
Outputs of similar age
#23,693
of 367,862 outputs
Outputs of similar age from BMC Systems Biology
#4
of 98 outputs
Altmetric has tracked 15,916,297 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,107 research outputs from this source. They receive a mean Attention Score of 3.4. This one has done particularly well, scoring higher than 98% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 367,862 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 98 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.