<i>In vitro</i> anti- <i>Helicobacter pylori</i> 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 <i>in vitro</i> antibacterial activity of ilaprazole against <i>Helicobacter pylori</i> (<i>H. pylori</i>), 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 <i>H</i>. <i>pylori</i> 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 <i>in vitro</i> antibacterial activity against <i>H. pylori</i>, 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 <i>in vitro</i> antibacterial activity of ilaprazole against <i>H. pylori</i>, 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 <i>H. pylori</i> infections, offering a compelling rationale for its clinical use. IMPORTANCE <i>H. pylori</i> 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 <i>in vitro</i> antibacterial activity of ilaprazole against <i>H. pylori</i>, 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 <i>H. pylori</i> management.