In vitro anti-Helicobacter pylori activity of ilaprazole used alone and in combination with other components of quadruple therapy.

Ilaprazole, a proton pump inhibitor, has been approved and marketed in Korea and China for the treatment of gastric ulcer, duodenal ulcer, gastroesophageal reflux disease, and erosive esophagitis. This study evaluated the in vitro antibacterial activity of ilaprazole against Helicobacter pylori (H. pylori), both as a single agent and in combination with other components used in the standard quadruple therapy. The antibacterial activity of ilaprazole was tested on 25 H. pylori strains, including the clinical isolates resistant to clarithromycin (CLA), amoxicillin (AMX), levofloxacin, and/or metronidazole. Antibacterial activities and killing kinetics were evaluated by the minimal inhibitory concentration (MIC) and time-kill curve determination, respectively. Synergistic effects were assessed in checkerboard and time-kill assays. Resistance development was assessed through serial passage over 12 cycles. Ilaprazole exhibited potent in vitro antibacterial activity against H. pylori, with MIC₅₀ and MIC₉₀ values of 8 µg/mL, demonstrating activity against drug-resistant strains. When combined with CLA, ilaprazole showed synergistic effects against 36% of the tested strains. Notably, the quadruple combination of ilaprazole + AMX + CLA + bismuth potassium citrate exhibited an obvious synergistic effect. Importantly, repeated exposure to ilaprazole over 12 passages did not induce resistance. These findings highlight the promising in vitro antibacterial activity of ilaprazole against H. pylori, including drug-resistant strains, and its potential to enhance the efficacy of quadruple therapy. The study supports the inclusion of ilaprazole in treatment regimens for H. pylori infections, offering a compelling rationale for its clinical use.IMPORTANCEH. pylori infection remains a major global health issue, contributing to a wide range of gastric diseases. Despite current treatment regimens, rising antibiotic resistance limits their effectiveness, emphasizing the need for novel therapeutic approaches. This study highlights the promising in vitro antibacterial activity of ilaprazole against H. pylori, including drug-resistant strains. Ilaprazole not only exhibits direct antimicrobial effects but also enhances the efficacy of combination therapy, particularly in quadruple therapy regimens, which are recommended as first-line treatment. The findings demonstrate that ilaprazole, in combination with clarithromycin, shows synergistic effects, offering a potential solution to overcome antibiotic resistance challenges. Importantly, repeated exposure to ilaprazole did not induce resistance, a critical factor for its long-term use. These results provide compelling evidence for ilaprazole's inclusion in clinical treatment strategies, contributing to improved eradication rates and better patient outcomes in H. pylori management.