Predicting the outcomes of new short-course regimens for multidrug-resistant tuberculosis using intrahost and pharmacokinetic-pharmacodynamic modeling

Tan N. Doan, Pengxing Cao, Theophilus I. Emeto, James M. McCaw, Emma S. McBryde

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Short-course regimens for multidrug-resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug bedaquiline (BDQ) may have the potential to shorten MDR-TB treatment to less than 6 months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modeling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modeling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (4 months) while still maintaining a very high treatment success rate (100% for daily BDQ for 2 weeks, or 95% for daily BDQ for 1 week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes, then we anticipate clear cost savings and a subsequent improvement in the efficiency of national TB programs.

Original languageEnglish
Article numbere01487-18
Number of pages11
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number12
DOIs
Publication statusPublished - Dec 2018
Externally publishedYes

Keywords

  • Bedaquiline
  • Mathematical modeling
  • Multidrug resistance
  • Short-course regimen
  • Tuberculosis

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