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

## TL;DR

Ilaprazole shows strong antibacterial effects against Helicobacter pylori, including drug-resistant strains, and works well in combination therapies without causing resistance.

## Contribution

Ilaprazole demonstrates synergistic effects in quadruple therapy and does not induce resistance, offering a novel approach to H. pylori treatment.

## Key findings

- Ilaprazole exhibited potent in vitro activity against H. pylori with MIC50 and MIC90 values of 8 µg/mL.
- Combining ilaprazole with clarithromycin showed synergistic effects in 36% of tested strains.
- Quadruple therapy with ilaprazole, amoxicillin, clarithromycin, and bismuth potassium citrate showed strong synergy.

## Abstract

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.

H. 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.