minocycline and bedaquiline

Non-tuberculous mycobacteria (NTM) infections are increasingly being reported worldwide. They are a major concern for healthcare professionals for multiple reasons, ranging from the intrinsic resistance of NTM to most conventionally utilized antimicrobials to inharmonious diagnostic criteria utilized for evaluation of NTM-infected patients, leading to high morbidity. In this review, we highlight the paucity of drugs having potent anti-NTM activity amongst the new antimicrobials currently under various stages of development for anti-tubercular activity and issue a call for the establishment of a concerted dedicated drug discovery pipeline targeting NTM.

Topics: Adamantane; Aminopyridines; Anti-Bacterial Agents; Azepines; Benzamides; Clinical Trials as Topic; Diarylquinolines; Drug Discovery; Ethylenediamines; Fluoroquinolones; Humans; Minocycline; Mycobacterium Infections, Nontuberculous; Nitroimidazoles; Nontuberculous Mycobacteria; Oxazoles; Piperazines; Spiro Compounds; Thiazines; Tigecycline; Uridine

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.. 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.. 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.. 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.

Topics: Animals; Anti-Bacterial Agents; Colony Count, Microbial; Diarylquinolines; Disease Models, Animal; Female; Kidney; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Microbial Sensitivity Tests; Minocycline; Mycobacterium; Mycobacterium Infections; Spleen; Statistics, Nonparametric; Tigecycline