The Activity of Moxifloxacin against Acid-Phase and Non-Replicative Persister Phenotype Phase Mycobacterium tuberculosis in a Hollow Fiber Infection Model [Experimental Therapeutics]

A major goal for improving tuberculosis therapy is to identify drug regimens with improved efficacy and shorter treatment durations. Shorter therapies improve patient adherence to the antibiotic regimens that, in turn, decreases resistance emergence.

M. tuberculosis exists in multiple metabolic states. At the initiation of therapy, the bulk of the population is in Log-Phase growth. Consequently, it is logical to focus initial therapy on these organisms. Moxifloxacin has good early bactericidal activity against Log-Phase growth bacteria and is a logical component of initial therapy. It would be optimal if this agent also possessed activity against Acid-Phase and Non-Replicative Persister (NRP) Phenotype organisms. We studied multiple exposures to moxifloxacin (equivalent to 200 mg-800 mg daily) in our Hollow Fiber Infection Model against strain H37Rv in Acid-Phase and against strain 18b in streptomycin starvation, which is a model for NRP-Phase organisms.

Moxifloxacin possesses good activity against Acid-Phase organisms, generating from 3.75 Log₁₀(CFU/ml) cell kill (200 mg daily) to 5.16 Log₁₀(CFU/ml) cell kill (800 mg daily) over the 28 days of the experiment.

Moxifloxacin also has activity against the streptomycin-starved strain 18b. The 400 to 800 mg daily regimens achieved extinction at day 28, while the no-treatment control still had 1.96 Log₁₀(CFU/ml) culturable. The lowest dose (200 mg daily) still had 0.7 Log₁₀(CFU/ml) measurable at day 28, a net kill of 1.26 Log₁₀(CFU/ml).

Moxifloxacin is an attractive agent for early therapy, as it possesses activity against three metabolic states of M. tuberculosis.

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