In Vitro Spectrum of Activity of Finafloxacin, a Novel, pH-Activated Fluoroquinolone, under Standard and Acidic Conditions

Abstract

Finafloxacin is a novel fluoroquinolone that exhibits enhanced antibacterial activity under acidic conditions. The aim of this study was to define the in vitro pH-activity relationship. Finafloxacin exhibited optimal antibacterial activity between pH 5.0 and 6.0 at which MICs were 4-to 8-fold lower than those determined at neutral pH. These observations were then confirmed against a larger collection of bacteria. These data suggest that finafloxacin could potentially offer a therapeutic advantage within acidic foci of infection.Fluoroquinolones are a widely utilized class of antibacterial agent. However, a number of attempts to develop new, more potent, members of this class have failed due to concerns over safety and tolerability that have resulted in a halt to development, withdrawal from the market, or restriction of the market (12). Finafloxacin is a new fluoroquinolone belonging to a novel 8-cyano subclass that exhibited a low potential for toxicity or tolerability issues in preclinical tests (14) and in later clinical trials (13). Finafloxacin was also highly effective when tested in in vivo infection models, perhaps more so than would have been predicted from its in vitro MIC (7,8). This effect was

Activity of the investigational fluoroquinolone finafloxacin and seven other antimicrobial agents against 114 obligately anaerobic bacteria

“…Finafloxacin shares a number of properties, e.g. broad spectrum of activity [1], rapid bactericidal action [2] and a low propensity to select for resistant variants [3], with currently marketed members of the fluoroquinolone class. However, a considerable divergence of antibacterial and pharmacodynamic properties exists amongst these different fluoroquinolones.…”

High Efficacy of Finafloxacin on Helicobacter pylori Isolates at pH 5.0 Compared with That of Other Fluoroquinolones

“…Finafloxacin has an advantage over other fluoroquinolones in terms of efficacy, especially for the acidic foci of infection (13,15), and has shown minimal toxicity issues during preclinical and clinical trials (15,16). Given that background, the present investigators assumed that finafloxacin might have better activity than conventional fluoroquinolones for treatment of H. pylori infections.…”

“…Usually, the efficacy of common fluoroquinolones is weakened in an acidic environment, but the efficacy of finafloxacin is not weakened under those conditions (13,14). The spectrum of in vitro activity and the antimicrobial efficacy of finafloxacin in many other microorganisms were demonstrated previously (13)(14)(15)(16). In addition, many studies have shown considerable finafloxacin antimicrobial efficacy under slightly acidic conditions, such as pH 5.0 (14,16).…”

Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones

“…This constitutes an advantage for the treatment of infections localized in an acidic environment like the urinary and genital tracts, the gastric mucosa, the airways of patients suffering from chronic inflammatory diseases, or abscesses (99) as well as against intracellular infections with phagolysosomal bacteria like S. aureus (98). Finafloxacin MICs against ciprofloxacin-susceptible or resistant Gram-negative bacteria are similar to those of ciprofloxacin at neutral pH but 3-5 dilutions lower at pH 5.2 (99)(100)(101)(102). It is, however, less active than ciprofloxacin on Pseudomonas aeruginosa or other ESKAPE pathogens like Klebsiella or Enterobacter spp.…”

“…It is, however, less active than ciprofloxacin on Pseudomonas aeruginosa or other ESKAPE pathogens like Klebsiella or Enterobacter spp. (101). In contrast to ciprofloxacin, finafloxacin is not a substrate for the fluoroquinolone efflux system by QepA1 of Escherichia coli (possibly related to its lower hydrophilicity) and is not affected the AAC(6')-Ib-cr acetylase, as it does not display the piperazine ring substrate for this enzyme in position 7 (100).…”