title: In vivo evaluation of antibiotic activity against Mycobacterium abscessus.
abstract: BACKGROUND
  The prognosis of Mycobacterium abscessus infections is poor due to the lack of effective drug treatment. The objective of this study was to set up an animal model suitable to test antibiotic activity against M. abscessus.
  
  
  METHODS
  The following mouse strains were evaluated: Swiss, BALB/c, C57BL/6, nude, beige, A/J, and GKO. Antibiotic activity was tested for clarithromycin, amikacin, cefoxitin, tigecycline, and bedaquiline (TMC207). Finally, we evaluated the 3-drug combination clarithromycin, cefoxitin, and amikacin.
  
  
  RESULTS
  Nude and GKO mice fulfilled criteria for the model but only nude mice offered sufficient availability for large therapeutic experiments. Among the 3 drugs usually combined for treatment of M. abscessus infection, cefoxitin was the most active because it improved survival and reduced bacillary loads in spleen whereas clarithromycin and amikacin prevented death but had little impact on bacillary loads. The triple-drug combination was not more active than cefoxitin alone. Tigecycline displayed bactericidal activity whereas bedaquiline was almost inactive.
  
  
  CONCLUSIONS
  Nude mice are an adequate model for in vivo chemotherapy studies. Among tested drugs, cefoxitin and tigecycline showed promising in vivo activity against M. abscessus. The best drug combination remains to be determined.
authors.affiliation: Laboratoire de Bactériologie-Hygiène, Faculté de Médecine, Université Pierre et Marie Curie.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lerat
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Cambau
authors.forename: Romain
authors.initials: R
authors.lastname: Roth Dit Bettoni
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gaillard
authors.forename: Vincent
authors.initials: V
authors.lastname: Jarlier
authors.forename: Chantal
authors.initials: C
authors.lastname: Truffot
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veziris
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D064687:Diarylquinolines / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007668:Kidney / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D009161:Mycobacterium / Q000187:drug effects*; D009164:Mycobacterium Infections / Q000188:drug therapy* / Q000382:microbiology*; D013154:Spleen / Q000382:microbiology; D018709:Statistics, Nonparametric; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D064687:Diarylquinolines; D000078304:Tigecycline; C493870:bedaquiline; D008911:Minocycline
keywords: Mycobacterium abscessus; TMC207; amikacin; bedaquiline; cefoxitin; clarithromycin; cystic fibrosis; murine model; nude mouse; tigecycline