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 journalArticlepeer-review

30 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 languageEnglish
Pages (from-to)448-455
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number2
Early online date25 Oct 2014
DOIs
Publication statusPublished - Feb 2015

Keywords

  • TTP
  • M. tuberculosis
  • TB

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