Figure 1.

Levofloxacin concentration-effect against Mycobacterium tuberculosis (Mtb). Mtb cultures were co-incubated for 7 days, with 3 replicates for each drug concentration. Shown are mean values; error bars are for standard deviation. The stasis line indicates bacterial burden at the start of treatment. Each drug concentration is expressed as a multiple of minimum inhibitory concentration (MIC). (A) Levofloxacin effect against extracellular log-phase growth Mtb demonstrated a steep decline in bacterial burden below the MIC, with no increased killing at the concentration of 1 times MIC or above. Maximal kill (E_max) was >7 log₁₀ colony-forming units (CFU)/mL below stasis. (B) We infected activated THP-1 cells and co-incubated them with levofloxacin for 7 days. The concentration-effect pattern was similar to that seen with extracellular Mtb co-incubation, with the difference that microbial kill below stasis was 2 log₁₀ CFU/mL less than against extracellular bacilli, which means less efficacy against intracellular bacilli. A lower E_max of intracellular vs extracellular Mtb has also been seen with other quinolones such as moxifloxacin. Abbreviations: MIC, minimum inhibitory concentration; Mtb, Mycobacterium tuberculosis.