Mechanisms and frequency of resistance to temafloxacin.

The bactericidal activity of temafloxacin and other fluoroquinolones is attributed to inhibition of bacterial DNA gyrase (topoisomerase II), an enzyme that regulates supercoiling and uncoiling of DNA. Because of this unique bactericidal mechanism of action, resistance to fluoroquinolones is limited to spontaneous mutations. In vitro studies were conducted to determine the frequency at which spontaneous resistance to temafloxacin occurs and to determine whether cross-resistance to other antimicrobial agents develops. In 13 strains of bacteria, the frequency of spontaneous resistance mutation to concentrations of temafloxacin at four and eight times the minimal inhibitory concentration (MIC) ranged from less than 1 x 10(-10) to 1.4 x 10(-7). Temafloxacin demonstrated a lower frequency of resistance to both methicillin-resistant and methicillin-sensitive Staphylococcus aureus compared with ciprofloxacin and ofloxacin. Cross resistance with other fluoroquinolones was observed.