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Difference in persi...
Difference in persistent tuberculosis bacteria between in vitro and sputum from patients : implications for translational predictions
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- Faraj, Alan (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Clewe, Oskar (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Svensson, Robin J. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Mukamolova, Galina V. (författare)
- Univ Leicester, Dept Resp Sci, Leicester TB Res Grp, Leicester, Leics, England.
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- Barer, Michael R. (författare)
- Univ Leicester, Dept Resp Sci, Leicester TB Res Grp, Leicester, Leics, England.;Univ Leicester, Dept Microbiol, Leicester, Leics, England.
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- Simonsson, Ulrika S. H., Professor (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- 2020-09-23
- 2020
- Engelska.
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Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- This study aimed to investigate the number of persistent bacteria in sputum from tuberculosis patients compared to in vitro and to suggest a model-based approach for accounting for the potential difference. Sputum smear positive patients (n=25) provided sputum samples prior to onset of chemotherapy. The number of cells detected by conventional agar colony forming unit (CFU) and most probable number (MPN) with Rpf supplementation were quantified. Persistent bacteria was assumed to be the difference between MPNrpf and CFU. The difference in persistent bacteria between in vitro and human sputum prior to chemotherapy was quantified using different model-based approaches. The persistent bacteria in sputum was 17% of the in vitro levels, suggesting a difference in phenotypic resistance, whereas no difference was found for multiplying bacterial subpopulations. Clinical trial simulations showed that the predicted time to 2 log fall in MPNrpf in a Phase 2a setting using in vitro pre-clinical efficacy information, would be almost 3 days longer if drug response was predicted ignoring the difference in phenotypic resistance. The discovered phenotypic differences between in vitro and humans prior to chemotherapy could have implications on translational efforts but can be accounted for using a model-based approach for translating in vitro to human drug response.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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