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

Abstract

Finafloxacin is a novel fluoroquinolone with improved antimicrobial efficacy, especially in an acidic environment. The efficacy of finafloxacin for the inhibition of Helicobacter pylori infection was compared with the efficacies of levofloxacin and moxifloxacin at neutral and acidic pH. The impacts of gyrA point mutation on the efficacy of those three fluoroquinolones were also investigated. A total of 128 clinical H. pylori strains were utilized. MICs of levofloxacin, moxifloxacin, and finafloxacin were determined at pH 5.0 and pH 7.0 by the agar dilution method. The impact of gyrA point mutations that are responsible for fluoroquinolone resistance was analyzed; the results showed 50 strains with an Asn-87 point mutation, 48 strains with an Asp-91 point mutation, and the remaining 30 strains with no gyrA mutations. The use of finafloxacin led to MIC values at pH 5.0 that were lower than the values seen at pH 7.0 for 112 strains (112/128, 87.5%), and this proportion was higher than that seen with moxifloxacin (21/128, 16.4%, P < 0.001). Finafloxacin also demonstrated a rate of susceptibility (MIC, <1 g/ml) (37.5%, 48/128) at pH 5.0 that was higher than that seen with moxifloxacin (2.3%, 3/128) (P < 0.001). The trends were similar regardless of which of the Asn-87, Asp-91, and A2143 point mutations were present. In conclusion, the superior antimicrobial efficacy of finafloxacin against H. pylori in an acidic environment suggests the possible use of finafloxacin for treatment of H. pylori infection, as has been proposed by its developer, Merlion Pharma. Helicobacter pylori infection is a cause of recurrent peptic ulcer disease, chronic gastritis, and gastric malignancies (1). It has been proven that the eradication of H. pylori can prevent peptic ulcer recurrence (2). However, drug instability and insufficient diffusion to gastric mucosa and mucus in that highly acidic environment require the combination of antibiotics with a proton pump inhibitor (PPI) for H. pylori eradication (3). PPI-clarithromycin-containing triple therapy was the first-line eradication treatment until recently (4). However, as the failure rate of the 7-day triple therapy has increased progressively, sequential or concomitant therapy has come to be used (3, 5). Unfortunately, the 7-day triple therapy is still regarded as the standard primary therapy in South Korea because there is no proven alternative regimen that can provide more efficient and safer eradication (6, 7). The unsatisfactory response of alternative eradication regimens was mainly caused by antimicrobial resistance and was particularly due to clarithromycin resistance (5, 8). Therefore, the Maastricht IV consensus has recommended that PPI-clarithromycin-containing triple therapy without prior susceptibility testing should be avoided when the clarithromycin resistance rate is higher than 15% to 20% (2). Moreover, the current high prevalence of metronidazole resistance in South Korea (9) indicates the necessity of reestablishment of a new standard first-line eradication therapy.In...

Antibiotics in the clinical pipeline at the end of 2015

“…90 Finafloxacin (9) is differentiated from other quinolones due to its improved activity at slightly acidic pH, which is more representative of physiological conditions. [91][92][93][94] Avycaz (CAZ104, CAZ-AVI) is a combination of the thirdgeneration cephalosporin ceftazidime (10) 95 and the new DBO-type β-lactamase inhibitor avibactam (11) [96][97][98] that has in vitro activity against Enterobacteriaceae in the presence of some β-lactamases and extended-spectrum β-lactamases (ESBLs) including AmpC, TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA), though it is not active against bacteria that produce metallo-β-lactamases or that overexpress efflux pumps. The combination restored the activity of ceftazidime in animal models of infection caused by ESBL, KPC and AmpC producing bacteria.…”

Discovery of a Novel Mutation in DNA Gyrase and Changes in the Fluoroquinolone Resistance of Helicobacter pylori over a 14-Year Period: A Single Center Study in Korea

“…The main mechanism of fluoroquinolone resistance in bacteria is to disrupt DNA replication by interfering with DNA gyrase or topoisomerase activities [22]. In fact, H. pylori do have neither parC nor parE genes, which encode topoisomerase IV, and a drug efflux system is considered not to have a major role in showing the resistance [24]. Thus, DNA gyrase has been considered responsible for fluoroquinolone resistance in H. pylori.…”

Risk factors of rescue bismuth quadruple therapy failure for Helicobacter pylori eradication

“…3,12,25 It has been reported that resistance to fluoroquinolone can significantly decrease the success rate of fluoroquinolone-containing therapy. 1,26,27 However, a clear relationship between resistance and treatment failure has not been found for metronidazole-containing treatment. 11 Metronidazole resistance reduces eradication rates by~25% in triple therapies but less in quadruple therapies when proton pump inhibitors are included in the regimen.…”

“…There is general consensus that the presence of clarithromycin resistance significantly impairs the efficacy of clarithromycin‐containing therapy . It has been reported that resistance to fluoroquinolone can significantly decrease the success rate of fluoroquinolone‐containing therapy . However, a clear relationship between resistance and treatment failure has not been found for metronidazole‐containing treatment .…”