Early Clinical Assessment of the Antimicrobial Activity of Finafloxacin Compared to Ciprofloxacin in Subsets of Microbiologically Characterized Isolates

Abstract

Two phase II studies were performed with patients with uncomplicated urinary tract infections (uUTIs) and complicated urinary tract infections (cUTIs) or acute pyelonephritis (PN) to compare finafloxacin (300 mg twice a day [b.i.d.] orally for uUTI and 800 mg once a day [q.d.] intravenously [i.v.] for cUTI/PN) and ciprofloxacin (250 mg b.i.d. orally for uUTI and 400 mg b.i.d. i.v. for cUTI/PN). The early response to the study medications was evaluated in the microbiological intent-to-treat population (mITT) at day 3. A total of 21% of the isolates were ciprofloxacin resistant, 13.7% were primed pathogens carrying a mutation(s) potentially fostering fluoroquinolone resistance development, and 7.1% produced extended-spectrum β-lactamases (ESBLs). Finafloxacin demonstrated very good early clinical activity, with microbiological eradication rates of 88.6% ( = 132), compared to 78.7% ( = 61) for ciprofloxacin, and 69.6% ( = 23), compared to 35.7% ( = 14) for ciprofloxacin, in patients with ciprofloxacin-resistant uropathogens; 94.1% ( = 17), compared to 80.0% ( = 10) for ciprofloxacin, in patients infected with uropathogens primed for fluoroquinolone resistance uropathogens; and 91.7% ( = 11), compared to 0% for ciprofloxacin, in patients infected with ESBL producers. Finafloxacin demonstrated early and rapid activity against uropathogens, including fluoroquinolone-resistant and/or multiresistant pathogens or ESBL producers, while ciprofloxacin was less active against this subset of resistant pathogens. Susceptibilities of pathogens were quantitated by broth microdilution. Isolates were subgrouped according to their susceptibility patterns, in particular first-step quinolone resistance, quinolone resistance, and ESBL production. Eradication was defined as the elimination or reduction of study entry pathogens to <10 CFU/ml in urine culture. (The studies described in this paper have been registered at ClinicalTrials.gov under identifiers NCT00722735 and NCT01928433.).

The Fluoroquinolone Finafloxacin Protects BALB/c Mice Against an Intranasal Infection With Francisella tularensis Strain SchuS4

“…One day of treatment with finafloxacin offered an extension in time to death when compared to ciprofloxacin and resulted in a reduction in bacterial load in the spleen, liver, and lungs. This again may be attributed to finafloxacin having a rapid and improved antibacterial activity in environments where ciprofloxacin is not as effective, demonstrated previously in vitro and more recently in urine samples infected with fluoroquinolone resistant pathogens (Lemaire et al, 2011; Vente et al, 2018). No differences were observed between finafloxacin and ciprofloxacin in terms of protection afforded in mice infected with F. tularensis or resulting bacterial load when the two antibiotics were administered for 3 or 7 days.…”

Demonstration of the Broad-Spectrum In Vitro Activity of Finafloxacin against Pathogens of Biodefense Interest

“…The availability of formulations of finafloxacin that can be delivered orally and systemically makes finafloxacin a worthy alternative for the treatment of a range of infections. In addition to good safety and efficacy data obtained in patients suffering from complicated urinary tract infections and pyelonephritis, previous studies have also demonstrated efficacy against the biothreat agents Burkholderia pseudomallei and Francisella tularensis in vitro and in vivo (6, 9–11). The aim of this study was to further evaluate the in vitro activity of finafloxacin against larger strain panels of biodefense pathogens.…”

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones—Shaping the Fifth Generation

“…At the same time, finafloxacin is in various stages of clinical trials to evaluate the efficacy of oral and intravenous formulations. These forms are intended for the treatment of uncomplicated and complicated urinary tract infections, pyelonephritis and Helicobacter pylori infections [ 99 , 144 , 145 , 146 , 147 ]. Finafloxacin has demonstrated broad-spectrum activity against a range of pathogens [ 148 ].…”