Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model

Sci Rep. 2018 Sep 10;8(1):13491. doi: 10.1038/s41598-018-31590-4.

Abstract

COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial colony forming units after 72 hours incubation). Celecoxib had no activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 ± 0.01ΔlogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA of standard TB drugs (mean cumulative WBA -0.10 ± 0.13ΔlogCFU versus -0.10 ± 0.12ΔlogCFU for TB drugs alone versus TB drugs and celecoxib; mean difference -0.01, 95% CI -0.02 to 0.00; p = 0.16). The lack of benefit of celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related responses are of limited importance in mycobacterial killing in the WBA assay.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use
  • Biological Assay
  • Blood Bactericidal Activity / drug effects
  • Celecoxib / pharmacology*
  • Celecoxib / therapeutic use
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Drug Administration Schedule
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • Female
  • Healthy Volunteers
  • Humans
  • Microbial Sensitivity Tests / methods
  • Mycobacterium tuberculosis / drug effects*
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Tuberculosis / drug therapy*
  • Tuberculosis / microbiology

Substances

  • Antitubercular Agents
  • Cyclooxygenase 2 Inhibitors
  • Celecoxib
  • Rifampin