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: OBJECTIVE
  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.
authors.affiliation: School of Medicine, University of St Andrews, Fife KY16 9AJ, UK rec9@st-andrews.ac.uk.
authors.forename: Ruth
authors.initials: R
authors.lastname: Bowness
authors.affiliation: Radboud University Medical Center, Department of Pulmonary Diseases, Nijmegen, The Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Boeree
authors.affiliation: Radboud University Medical Center, Department of Clinical Pharmacy, Nijmegen, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Aarnoutse
authors.affiliation: Division of Pulmonology, Department of Medicine and University of Cape Town Lung Institute, Cape Town, South Africa.
authors.forename: Rodney
authors.initials: R
authors.lastname: Dawson
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Andreas
authors.initials: A
authors.lastname: Diacon
authors.affiliation: NIMR-Mbeya Medical Research Centre, PO Box 2410, Mbeya, Tanzania.
authors.forename: Chacha
authors.initials: C
authors.lastname: Mangu
authors.affiliation: Department for Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany DZIF German Centre for Infection Research, Munich, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Heinrich
authors.affiliation: NIMR-Mbeya Medical Research Centre, PO Box 2410, Mbeya, Tanzania.
authors.forename: Nyanda E
authors.initials: NE
authors.lastname: Ntinginya
authors.affiliation: NIMR-Mbeya Medical Research Centre, PO Box 2410, Mbeya, Tanzania Department for Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Kohlenberg
authors.affiliation: NIMR-Mbeya Medical Research Centre, PO Box 2410, Mbeya, Tanzania.
authors.forename: Bariki
authors.initials: B
authors.lastname: Mtafya
authors.affiliation: Medical Research Council (MRC) Clinical Trials Unit at UCL, London, UK.
authors.forename: Patrick P J
authors.initials: PP
authors.lastname: Phillips
authors.affiliation: Department for Infectious Diseases and Tropical Medicine, University of Munich, Munich, Germany DZIF German Centre for Infection Research, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rachow
authors.affiliation: Radboud University Medical Center, Department of Pulmonary Diseases, Nijmegen, The Netherlands.
authors.forename: Georgette
authors.initials: G
authors.lastname: Plemper van Balen
authors.affiliation: School of Medicine, University of St Andrews, Fife KY16 9AJ, UK.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gillespie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use; D058491:Bacterial Load; D066264:Datasets as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D010641:Phenotype; D013183:Sputum / Q000382:microbiology*; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents
keywords: M. tuberculosis; TB; TTP