finafloxacin and Urinary-Tract-Infections

Finafloxacin is a fluoroquinolone antimicrobial agent that exhibits optimum efficacy in slightly acidic environments. It is being developed by MerLion Pharmaceuticals to treat serious bacterial infections associated with an acidic environment, including urinary tract infections and Helicobacter pylori infections. An otic suspension of finafloxacin (Xtoro™), developed by Alcon (a division of Novartis), was recently approved in the USA for the treatment of acute otitis externa, and a Common Technical Document for this indication was also filed in Canada. Oral and/or intravenous formulations are in phase I and II evaluation in uncomplicated urinary tract infections (Germany and Singapore), complicated urinary tract infections and pyelonephritis (Germany and Poland) and H. pylori infection (Germany). This article summarizes the milestones in the development of finafloxacin leading to this first approval for otitis externa.

Topics: Animals; Anti-Bacterial Agents; Drug Approval; Fluoroquinolones; Helicobacter pylori; Humans; Internationality; Microbial Sensitivity Tests; Otitis Externa; Urinary Tract Infections

In the past decade, the indiscriminate use of fluoroquinolones in the prophylaxis and treatment of urinary tract infections (UTIs) has led to an increase of antibiotic resistance patterns. Finafloxacin is a new generation fluoroquinolone with interesting preclinical characteristics and pH-related efficacy.. This review summarizes finafloxacin's safety profile and prospectively evaluates its specific use in the treatment of UTIs. This article was based on a Medline English literature search.. In vitro and in vivo studies have shown that finafloxacin expresses its full antibacterial activity in acidic environments and is able to exert significant bactericidal effects in difficult-to-treat infections. Finafloxacin has a broad antibacterial spectrum and efficient pharmacokinetic absorption. Moreover, it undergoes extensive tissue distribution, resulting in good antibacterial activity for daily dosages from 400 to 800 mg. This novel compound has also been successfully tested on biofilm-related Escherichia coli. Finafloxacin has demonstrated a good safety and tolerability profile in humans when administered orally or intravenously and is thus an interesting compound for the treatment of UTIs. However, further prospective randomized clinical trials will be necessary to confirm these preliminary results before definitive conclusions can be made.

Topics: Animals; Anti-Infective Agents, Urinary; Fluoroquinolones; Humans; Urinary Tract Infections

The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic conditions. This phase II clinical study compared the efficacies and safeties of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with 800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a 10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68% for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients (64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent-to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin on patients with an acidic urine pH (80% of patients) were reduced, whereas the effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated. Overall, 43.4% of the patients in the FINA05 group, 42.7% in the FINA10 group, and 54.2% in the CIPRO10 group experienced mostly mild and treatment-emergent but unrelated adverse events. A short-course regimen of 5 days of finafloxacin resulted in high eradication and improved clinical outcome rates compared to those for treatment with ciprofloxacin for 10 days. In contrast to those of ciprofloxacin, the clinical effects of finafloxacin were not reduced by acidic urine pH. Hospitalized adults were randomized 1:1:1 to finafloxacin treatment (800 mg q.d.) for either 5 or 10 days or to ciprofloxacin treatment (400 mg/500 mg b.i.d.) for 10 days with an optional switch from intravenous (i.v.) to oral administration at day 3. The primary endpoint was the combined microbiological and clinical response at the TOC visit in the microbiological intent-to-treat population. (This study has been registered at ClinicalTrials.gov under identifier NCT01928433.).

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Ciprofloxacin; Female; Fluoroquinolones; Humans; Male; Middle Aged; Pyelonephritis; Urinary Tract Infections

The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing

Topics: Anti-Bacterial Agents; beta-Lactamases; Blood; Ciprofloxacin; Escherichia coli; Fluoroquinolones; Humans; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests; Urinary Tract Infections; Urine