title: Improving existing tools for Mycobacterium xenopi treatment: assessment of drug combinations and characterization of mouse models of infection and chemotherapy.
abstract: BACKGROUND
  Mycobacterium xenopi is a common agent of non-tuberculous mycobacterial lung diseases in Europe. However, an optimal treatment regimen for M. xenopi infection has not yet been established. Appropriate in vitro and in vivo model systems are needed for characterization of the activity of potential drugs and drug combinations against M. xenopi.
  
  
  METHODS
  We utilized three experimental platforms to analyse the anti-M. xenopi activity of single and combination drug regimens. First, we determined the bacteriostatic and bactericidal activities of drugs alone and in combination in vitro. Second, we used serum from treated mice to evaluate drug activities ex vivo. Third, we analysed M. xenopi growth in four strains of mice (BALB/c, C57BL/6, beige and athymic nude) and developed a mouse model of chemotherapy for this infection.
  
  
  RESULTS
  Two-drug combinations of ethambutol with rifampicin, rifapentine or moxifloxacin, and of clarithromycin with moxifloxacin were bactericidal in vitro, and the combination of ethambutol and rifampicin with either clarithromycin or moxifloxacin showed significant bactericidal activity ex vivo. Nude mice were the most susceptible strain to M. xenopi infection, and in this model amikacin-containing regimens were the most effective against M. xenopi. No difference in activity was found between regimens containing clarithromycin and moxifloxacin in vivo.
  
  
  CONCLUSIONS
  The ethambutol/rifampicin combination with clarithromycin or moxifloxacin had significant bactericidal activity against M. xenopi. The nude mouse, being highly susceptible to M. xenopi, can be utilized for in vivo chemotherapy studies for this infection.
authors.affiliation: Johns Hopkins University School of Medicine, Center for Tuberculosis Research, 1550 Orleans Street, Baltimore, MD 21231, USA. clandrejak@gmail.com
authors.forename: Claire
authors.initials: C
authors.lastname: Andréjak
authors.forename: Deepak V
authors.initials: DV
authors.lastname: Almeida
authors.forename: Sandeep
authors.initials: S
authors.lastname: Tyagi
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Converse
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Ammerman
authors.forename: Jacques H
authors.initials: JH
authors.lastname: Grosset
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy*; D019912:Mycobacterium xenopi / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000995:Antitubercular Agents