The FDA's rationale for approving bedaquiline in MDR-TB via the Breakthrough Therapy pathway created by the GAIN legislation - on the basis of preliminary Phase II evidence of culture-conversion - included this:
[ Nonetheless, treatment for resistant TB is complex, costly, toxic and prolonged, requiring at least 5 second-line drugs for up to 2 years. Second-line drugs include injectable drugs (amikacin, kanamycin, capreomycin) and oral fluoroquinolones (FQs) and other second line drugs; the optimal use of which has not been well studied in randomized controlled trials, and whose safety when used in concert with various doses and regimens is not sufficiently described. ]
Note the "... and whose safety when used in concert with various doses and regimens is not sufficiently described."
Bedaquiline and the mainstay antibiotics used to treat the 12 million people Worldwide at any given moment with active TB infection are tablets.
They rely upon building a concentration of the drug in the bloodstream - and then maintaining it for as long as it takes for enough antibiotic to move from the bloodstream into the airways in the lungs, and then into the pulmonary macrophages to kill the mycobacteria sheltering within.
The immune system of a normal healthy individual is easily capable of suppressing potentially harmful concentrations of bacteria in the body.
When that isn't happening it's because there's an underlying problem, e.g. old age, malnutrition, Cystic Fibrosis, Non-CF bronchiectasis, COPD, AIDS and other debilitating conditions.
Pulmonary mycobacterial infection is a major killer in AIDS. People being treated for AIDS are walking around with a cocktail of drugs in the bloodstream.
Hence the FDA concerns. Few, if any, of the antibiotics currently used to treat TB have been in clinical trials to establish the adverse effects resulting from interaction with, and cumulative toxicity from, other drugs in the bloodstream.