In Vivo Evaluation of Antibiotic Activity Against Mycobacterium abscessus

• Published in: The Journal of infectious diseases Vol. 209; no. 6; pp. 905 - 912
• Main Authors: Lerat, Isabelle, Cambau, Emmanuelle, Bettoni, Romain Roth dit, Gaillard, Jean-Louis, Jarlier, Vincent, Truffot, Chantal, Veziris, Nicolas
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.03.2014
• Subjects: Animal models; Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Biological and medical sciences; Colony Count, Microbial; Diarylquinolines - pharmacology; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Fungal infections; Infections; Infectious diseases; Kidney - microbiology; Kidneys; Lesions; Liver; Lung - microbiology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Nude; Microbial Sensitivity Tests; Microbiology; Minocycline - analogs & derivatives; Minocycline - pharmacology; Mycobacterium; Mycobacterium - drug effects; Mycobacterium Infections - drug therapy; Mycobacterium Infections - microbiology; Spleen; Spleen - microbiology; Statistics, Nonparametric; Infection; Antibiotic; Mycobacteriales; Mycobacteriaceae; Bacteria; Actinomycetes; Mycobacterium abscessus; amikacin; cefoxitin; nude mouse; cystic fibrosis; tigecycline; clarithromycin; murine model; TMC207; bedaquiline
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jit614

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.