Skip to main content

Advertisement

SpringerLink
Log in

Time to detection of the growth of Mycobacterium tuberculosis in MGIT 960 for determining the early bactericidal activity of antituberculosis agents

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Evaluation of early bactericidal activity (EBA) by the determination of a fall in viable colony-forming units (CFU) of Mycobacterium tuberculosis in sputum is a first step in the clinical study of new antituberculosis agents. The time to detection (TTD) of growth in liquid media is more sensitive and could substitute for CFU counting on solid media. Overnight sputum samples collected during the evaluation of the novel agent TMC207 in comparison to isoniazid and rifampicin were studied. For the determination of CFU, we incubated 10-fold dilutions of homogenized sputum on selective 7H10 agar. The TTD was measured by incubating decontaminated sputum in the BACTEC MGIT 960 system. The fall in bacillary load over 7 days determined by CFU counting closely matched the prolongation of the TTD in the BACTEC MGIT 960 system. The CFU counts correlated significantly with the TTD. While the ranking of agents and different dosages of TMC207 was similar, the highest dose of TMC207 showed markedly better activity when measured by the TTD than CFU counting when compared to the activity of isoniazid. Automated TTD could augment, or, in future, replace, CFU counting to determine sputum bacillary load in EBA clinical trials pending a more formal evaluation of the correlation of the measurements.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Mitchison DA, Sturm WA (1997) The measurement of early bactericidal activity. In: Malin A, McAdam K (eds) Bailliere’s Clinical Infectious Diseases: Mycobacterial Diseases Part II. Bailliere Tindall, London, pp 185–206

    Google Scholar 

  2. Global Alliance for TB Drug Development (2001) Tuberculosis. Scientific blueprint for tuberculosis drug development. Tuberculosis (Edinb) 81(Suppl 1):1–52

    Google Scholar 

  3. Donald PR, Sirgel FA, Venter A, Parkin DP, Seifart HI, van de Wal BW, Maritz JS, Fourie PB (2003) Early bactericidal activity of antituberculosis agents. Expert Rev Anti Infect Ther 1:141–155

    Article  CAS  PubMed  Google Scholar 

  4. Donald PR, Diacon AH (2008) The early bactericidal activity of anti-tuberculosis drugs: a literature review. Tuberculosis (Edinb) 88(Suppl 1):S75–S83

    Article  CAS  Google Scholar 

  5. Jindani A, Aber VR, Edwards EA, Mitchison DA (1980) The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis 121:939–949

    CAS  PubMed  Google Scholar 

  6. Somoskövi A, Magyar P (1999) Comparison of the mycobacteria growth indicator tube with MB redox, Löwenstein–Jensen, and Middlebrook 7H11 media for recovery of mycobacteria in clinical specimens. J Clin Microbiol 37:1366–1369

    PubMed  Google Scholar 

  7. Pfyffer GE, Welscher HM, Kissling P, Cieslak C, Casal MJ, Gutierrez J, Rüsch-Gerdes S (1997) Comparison of the Mycobacteria Growth Indicator Tube (MGIT) with radiometric and solid culture for recovery of acid-fast bacilli. J Clin Microbiol 35:364–368

    CAS  PubMed  Google Scholar 

  8. Hanna BA, Ebrahimzadeh A, Elliott LB, Morgan MA, Novak SM, Rüsch-Gerdes S, Acio M, Dunbar DF, Holmes TM, Rexer CH, Savthyakumar C, Vannier AM (1999) Multicenter evaluation of the BACTEC MGIT 960 system for recovery of mycobacteria. J Clin Microbiol 37:748–752

    CAS  PubMed  Google Scholar 

  9. Epstein MD, Schluger NW, Davidow AL, Bonk S, Rom WN, Hanna B (1998) Time to detection of Mycobacterium tuberculosis in sputum culture correlates with outcome in patients receiving treatment for pulmonary tuberculosis. Chest 113:379–386

    Article  CAS  PubMed  Google Scholar 

  10. Carroll NM, Uys P, Hesseling A, Lawrence K, Pheiffer C, Salker F, Duncan K, Beyers N, van Helden PD (2008) Prediction of delayed treatment response in pulmonary tuberculosis: use of time to positivity values of Bactec cultures. Tuberculosis (Edinb) 88:624–630

    Article  CAS  Google Scholar 

  11. Pheiffer C, Carroll NM, Beyers N, Donald P, Duncan K, Uys P, van Helden P (2008) Time to detection of Mycobacterium tuberculosis in BACTEC systems as a viable alternative to colony counting. Int J Tuberc Lung Dis 12:792–798

    CAS  PubMed  Google Scholar 

  12. Andries K, Verhasselt P, Guillemont J, Göhlmann HW, Neefs JM, Winkler H, Van Gestel J, Timmerman P, Zhu M, Lee E, Williams P, de Chaffoy D, Huitric E, Hoffner S, Cambau E, Truffot-Pernot C, Lounis N, Jarlier V (2005) A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307:223–227

    Article  CAS  PubMed  Google Scholar 

  13. Matteelli A, Carvalho AC, Dooley KE, Kritski A (2010) TMC207: the first compound of a new class of potent anti-tuberculosis drugs. Future Microbiol 5:849–858

    Article  CAS  PubMed  Google Scholar 

  14. Rustomjee R, Diacon AH, Allen J, Venter A, Reddy C, Patientia RF, Mthiyane TC, De Marez T, van Heeswijk R, Kerstens R, Koul A, De Beule K, Donald PR, McNeeley DF (2008) Early bactericidal activity and pharmacokinetics of the diarylquinoline TMC207 in treatment of pulmonary tuberculosis. Antimicrob Agents Chemother 52:2831–2835

    Article  CAS  PubMed  Google Scholar 

  15. Lounis N, Gevers T, Van Den Berg J, Verhaeghe T, van Heeswijk R, Andries K (2008) Prevention of drug carryover effects in studies assessing antimycobacterial efficacy of TMC207. J Clin Microbiol 46:2212–2215

    Article  CAS  PubMed  Google Scholar 

  16. Mitchison DA, Coates AR (2004) Predictive in vitro models of the sterilizing activity of anti-tuberculosis drugs. Curr Pharm Des 10:3285–3295

    Article  CAS  PubMed  Google Scholar 

  17. Dhillon J, Lowrie DB, Mitchison DA (2004) Mycobacterium tuberculosis from chronic murine infections that grows in liquid but not on solid medium. BMC Infect Dis 4:51

    Article  PubMed  Google Scholar 

  18. Peres RL, Maciel EL, Morais CG, Ribeiro FC, Vinhas SA, Pinheiro C, Dietze R, Johnson JL, Eisenach K, Palaci M (2009) Comparison of two concentrations of NALC-NaOH for decontamination of sputum for mycobacterial culture. Int J Tuberc Lung Dis 13:1572–1575

    CAS  PubMed  Google Scholar 

  19. Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, Pistorius C, Krause R, Bogoshi M, Churchyard G, Venter A, Allen J, Palomino JC, De Marez T, van Heeswijk RP, Lounis N, Meyvisch P, Verbeeck J, Parys W, de Beule K, Andries K, McNeeley DF (2009) The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med 360:2397–2405

    Article  CAS  PubMed  Google Scholar 

  20. Li L, Mahan CS, Palaci M, Horter L, Loeffelholz L, Johnson JL, Dietze R, Debanne SM, Joloba ML, Okwera A, Boom WH, Eisenach KD (2010) Sputum Mycobacterium tuberculosis mRNA as a marker of bacteriologic clearance in response to antituberculosis therapy. J Clin Microbiol 48:46–51

    Article  CAS  PubMed  Google Scholar 

  21. Wallis RS, Doherty TM, Onyebujoh P, Vahedi M, Laang H, Olesen O, Parida S, Zumla A (2009) Biomarkers for tuberculosis disease activity, cure, and relapse. Lancet Infect Dis 9:162–172

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest statement

Tibotec sponsored the study from which a subset of data is analyzed in this report [14]. DFM and KA are employees of Tibotec, the manufacturer of TMC207. All other authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Human Genetics, and the MRC Centre for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa

    A. H. Diacon, J. S. Maritz, A. Venter & P. D. van Helden

  2. Tibotec BVBA, Mechelen, Belgium

    K. Andries

  3. Tibotec, Inc., Titusville, NJ, USA

    D. F. McNeeley

  4. Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Tygerberg, South Africa

    P. R. Donald

  5. Division of Physiology, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, P.O. Box 19063, 7505, Tygerberg, South Africa

    A. H. Diacon

Authors
  1. A. H. Diacon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. S. Maritz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Venter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. D. van Helden
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Andries
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. F. McNeeley
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. R. Donald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. H. Diacon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Diacon, A.H., Maritz, J.S., Venter, A. et al. Time to detection of the growth of Mycobacterium tuberculosis in MGIT 960 for determining the early bactericidal activity of antituberculosis agents. Eur J Clin Microbiol Infect Dis 29, 1561–1565 (2010). https://doi.org/10.1007/s10096-010-1043-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-010-1043-7

Keywords

Search

Navigation