Comparative in vitro activities of the new quinolone nemonoxacin (TG-873870), gemifloxacin and other quinolones against clinical isolates of Mycobacterium tuberculosis

Sir, The emergence of resistance of Mycobacterium tuberculosis to fluoroquinolones in patients with newly diagnosed infection has been a concern, especially in patients who have prior exposure to fluoroquinolones.1 Furthermore, the usage of fluoroquinolones in community-acquired infection has been reported to delay the diagnosis of tuberculosis (TB).2,3 The development of a new quinolone that retains the antibacterial activity spectrum of classic fluoroquinolones but with a relatively low activity against M. tuberculosis might have a role to play in removing the concern of potentially delaying the diagnosis of TB. Nemonoxacin (TG-873870) is a non-fluorinated quinolone that is currently being developed in oral and intravenous formulations. This agent has good in vitro activities against major pathogens from respiratory tract and skin infections, including penicillin-resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. This agent differs from fluoroquinolones in that it lacks the fluorine in the C6 position; the fluorine atom at C6 improves cell penetration and gyrase affinity.4 Nemonoxacin acts by inhibiting bacterial DNA gyrase and topoisomerase IV and retains potent broad-spectrum activities against Gram-positive and -negative bacteria.5 As there is no evidence of the topoisomerase IV gene in the genome of M. tuberculosis, gyrase appears to be the sole target for quinolones in M. tuberculosis.4,6