Selected Mutations by Nemonoxacin and Fluoroquinolone Exposure Among Relevant Gram-Positive Bacterial Strains in Taiwan

Abstract

Nemonoxacin is a nonfluorinated quinolone with good bactericidal effects against quinolone-resistant Gram-positive microorganisms. The <i>in vitro</i> inducible resistance of nemonoxacin against clinically relevant Gram-positive pathogens was compared with ciprofloxacin, levofloxacin, and moxifloxacin. Three strains of each bacterial species, including <i>Streptococcus pneumoniae</i>, <i>Staphylococcus aureus</i>, <i>Enterococcus faecium</i>, and <i>Enterococcus faecalis</i>, were cultured. All clinical isolates had wild-type <i>gyrA</i>, <i>gyrB</i> and <i>parC</i>, <i>parE</i> before further <i>in vitro</i> test. DNA sequencing for the quinolone resistance determination region (QRDR) of gyrase and topoisomerase genes was performed. Nemonoxacin had the lowest minimum inhibitory concentrations (MICs) among all quinolones. During exposure to nemonoxacin, the MIC values did not increase for <i>S. aureus</i>, <i>E. faecium</i>, and <i>E. faecalis</i>, and revealed fourfold increase of <i>S. pneumoniae</i> over three cycles of a stepwise resistance selection. DNA sequencing did not show inducible QRDR resistance of nemonoxacin group. Compared to other fluoroquinolones, nemonoxacin has a low potential for inducing resistant pathogens.