The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations

Ruth Bowness; Martin J Boeree; Rob Aarnoutse; Rodney Dawson; Andreas Diacon; Chacha Mangu; Norbert Heinrich; Nyanda E Ntinginya; Anke Kohlenberg; Bariki Mtafya; Patrick P J Phillips; Andrea Rachow; Georgette Plemper van Balen; Stephen H Gillespie

doi:10.1093/jac/dku415

The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations

Ruth Bowness, Martin J Boeree, Rob Aarnoutse, Rodney Dawson, Andreas Diacon, Chacha Mangu, Norbert Heinrich, Nyanda E Ntinginya, Anke Kohlenberg, Bariki Mtafya, Patrick P J Phillips, Andrea Rachow, Georgette Plemper van Balen, Stephen H Gillespie

Research output: Contribution to journal › Article › peer-review

54 Citations (Scopus)

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Abstract

Objectives

The relationship between cfu and Mycobacterial Growth Indicator Tube (MGIT) time to positivity (TTP) is uncertain. We attempted to understand this relationship and create a mathematical model to relate these two methods of determining mycobacterial load.

Methods

Sequential bacteriological load data from clinical trials determined by MGIT and cfu were collected and mathematical models derived. All model fittings were conducted in the R statistical software environment (version 3.0.2), using the lm and nls functions.

Results

TTP showed a negative correlation with log₁₀ cfu on all 14 days of the study. There was an increasing gradient of the regression line and y-intercept as treatment progressed. There was also a trend towards an increasing gradient with higher doses of rifampicin.

Conclusions

These data suggest that there is a population of mycobacterial cells that are more numerous when detected in liquid than on solid medium. Increasing doses of rifampicin differentially kill this group of organisms. These findings support the idea that increased doses of rifampicin are more effective.

Original language	English
Pages (from-to)	448-455
Number of pages	8
Journal	Journal of Antimicrobial Chemotherapy
Volume	70
Issue number	2
Early online date	25 Oct 2014
DOIs	https://doi.org/10.1093/jac/dku415
Publication status	Published - Feb 2015

Keywords

TTP
M. tuberculosis
TB

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/jac/dku415

bowness2014jantimicrobchemo-accepted
© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Antimicrobial Chemotherapy following peer review. The version of record The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations, Bowness, R., Boeree, M. J., Aarnoutse, R., Dawson, R., Diacon, A., Mangu, C., Heinrich, N., Ntinginya, N. E., Kohlenberg, A., Mtafya, B., Phillips, P. P. J., Rachow, A., Plemper van Balen, G. & Gillespie, S. H. 2014 In : Journal of Antimicrobial Chemotherapy is available online at: http://jac.oxfordjournals.org/content/early/2014/10/24/jac.dku415.abstract
Accepted author manuscript, 803 KB
bowness2014jantimicrobchemo-accepted-supplementAccepted author manuscript, 481 KB

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1 Finished

IMI PREDICT TB 100%: IMI Pre-DiCT-TB
Gillespie, S. H. (PI)
European Commission
1/05/12 → 31/10/17
Project: Standard

Stephen Henry Gillespie
- shg3st-andrews.acuk
Person: Academic

Cite this

Bowness, R., Boeree, M. J., Aarnoutse, R., Dawson, R., Diacon, A., Mangu, C., Heinrich, N., Ntinginya, N. E., Kohlenberg, A., Mtafya, B., Phillips, P. P. J., Rachow, A., Plemper van Balen, G., & Gillespie, S. H. (2015). The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations. Journal of Antimicrobial Chemotherapy, 70(2), 448-455. https://doi.org/10.1093/jac/dku415

@article{604a7382f89c43ab8255da83fa3fdf50,

title = "The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations",

abstract = "ObjectivesThe relationship between cfu and Mycobacterial Growth Indicator Tube (MGIT) time to positivity (TTP) is uncertain. We attempted to understand this relationship and create a mathematical model to relate these two methods of determining mycobacterial load.MethodsSequential bacteriological load data from clinical trials determined by MGIT and cfu were collected and mathematical models derived. All model fittings were conducted in the R statistical software environment (version 3.0.2), using the lm and nls functions.ResultsTTP showed a negative correlation with log10 cfu on all 14 days of the study. There was an increasing gradient of the regression line and y-intercept as treatment progressed. There was also a trend towards an increasing gradient with higher doses of rifampicin.ConclusionsThese data suggest that there is a population of mycobacterial cells that are more numerous when detected in liquid than on solid medium. Increasing doses of rifampicin differentially kill this group of organisms. These findings support the idea that increased doses of rifampicin are more effective.",

keywords = "TTP, M. tuberculosis, TB",

author = "Ruth Bowness and Boeree, {Martin J} and Rob Aarnoutse and Rodney Dawson and Andreas Diacon and Chacha Mangu and Norbert Heinrich and Ntinginya, {Nyanda E} and Anke Kohlenberg and Bariki Mtafya and Phillips, {Patrick P J} and Andrea Rachow and {Plemper van Balen}, Georgette and Gillespie, {Stephen H}",

note = "This work was supported by EDCTP who fund the PanACEA consortium (IP.2007.32011.011, IP.2007.32011.012, IP.2007.32011.013) and PreDiCT-TB consortium [IMI Joint undertaking grant agreement number 115337, resources of which are composed of financial contribution from the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies{\textquoteright} in kind contribution].",

year = "2015",

month = feb,

doi = "10.1093/jac/dku415",

language = "English",

volume = "70",

pages = "448--455",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

publisher = "Oxford University Press",

number = "2",

}

Bowness, R, Boeree, MJ, Aarnoutse, R, Dawson, R, Diacon, A, Mangu, C, Heinrich, N, Ntinginya, NE, Kohlenberg, A, Mtafya, B, Phillips, PPJ, Rachow, A, Plemper van Balen, G & Gillespie, SH 2015, 'The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations', Journal of Antimicrobial Chemotherapy, vol. 70, no. 2, pp. 448-455. https://doi.org/10.1093/jac/dku415

The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations. / Bowness, Ruth; Boeree, Martin J; Aarnoutse, Rob et al.
In: Journal of Antimicrobial Chemotherapy, Vol. 70, No. 2, 02.2015, p. 448-455.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations

AU - Bowness, Ruth

AU - Boeree, Martin J

AU - Aarnoutse, Rob

AU - Dawson, Rodney

AU - Diacon, Andreas

AU - Mangu, Chacha

AU - Heinrich, Norbert

AU - Ntinginya, Nyanda E

AU - Kohlenberg, Anke

AU - Mtafya, Bariki

AU - Phillips, Patrick P J

AU - Rachow, Andrea

AU - Plemper van Balen, Georgette

AU - Gillespie, Stephen H

N1 - This work was supported by EDCTP who fund the PanACEA consortium (IP.2007.32011.011, IP.2007.32011.012, IP.2007.32011.013) and PreDiCT-TB consortium [IMI Joint undertaking grant agreement number 115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution].

PY - 2015/2

Y1 - 2015/2

N2 - ObjectivesThe relationship between cfu and Mycobacterial Growth Indicator Tube (MGIT) time to positivity (TTP) is uncertain. We attempted to understand this relationship and create a mathematical model to relate these two methods of determining mycobacterial load.MethodsSequential bacteriological load data from clinical trials determined by MGIT and cfu were collected and mathematical models derived. All model fittings were conducted in the R statistical software environment (version 3.0.2), using the lm and nls functions.ResultsTTP showed a negative correlation with log10 cfu on all 14 days of the study. There was an increasing gradient of the regression line and y-intercept as treatment progressed. There was also a trend towards an increasing gradient with higher doses of rifampicin.ConclusionsThese data suggest that there is a population of mycobacterial cells that are more numerous when detected in liquid than on solid medium. Increasing doses of rifampicin differentially kill this group of organisms. These findings support the idea that increased doses of rifampicin are more effective.

AB - ObjectivesThe relationship between cfu and Mycobacterial Growth Indicator Tube (MGIT) time to positivity (TTP) is uncertain. We attempted to understand this relationship and create a mathematical model to relate these two methods of determining mycobacterial load.MethodsSequential bacteriological load data from clinical trials determined by MGIT and cfu were collected and mathematical models derived. All model fittings were conducted in the R statistical software environment (version 3.0.2), using the lm and nls functions.ResultsTTP showed a negative correlation with log10 cfu on all 14 days of the study. There was an increasing gradient of the regression line and y-intercept as treatment progressed. There was also a trend towards an increasing gradient with higher doses of rifampicin.ConclusionsThese data suggest that there is a population of mycobacterial cells that are more numerous when detected in liquid than on solid medium. Increasing doses of rifampicin differentially kill this group of organisms. These findings support the idea that increased doses of rifampicin are more effective.

KW - TTP

KW - M. tuberculosis

KW - TB

U2 - 10.1093/jac/dku415

DO - 10.1093/jac/dku415

M3 - Article

C2 - 25344806

SN - 0305-7453

VL - 70

SP - 448

EP - 455

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 2

ER -

Bowness R, Boeree MJ, Aarnoutse R, Dawson R, Diacon A, Mangu C et al. The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations. Journal of Antimicrobial Chemotherapy. 2015 Feb;70(2):448-455. Epub 2014 Oct 25. doi: 10.1093/jac/dku415

The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations

Abstract

Keywords

UN SDGs

Access to Document

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Projects

IMI PREDICT TB 100%: IMI Pre-DiCT-TB

Profiles

Stephen Henry Gillespie

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