BACKGROUND/AIMS: Although proton pump inhibitors (PPIs) have been widely used for the prevention and treatment of stress gastric ulcers in hospital settings, there are concerns that PPIs increase the risk of Clostridium difficile infection (CDI). However, little is known about the risk of CDI following PPI and histamine-2 receptor antagonist (H2RA) use. We evaluated the comparative hospital-acquired CDI occurrence risk associated with the concurrent use of PPIs versus H2RAs. METHODS: A systematic search of PubMed, MEDLINE/Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Google Scholar through August 19, 2016, identified 12 studies that reported the hospital-acquired CDI occurrence following H2RA and PPI use for the prevention and treatment of stress gastric ulcers. Random-effects pooled odds ratios and 95% confidence intervals were estimated. Heterogeneity was measured using I², and a meta-regression analysis was conducted. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the overall quality of the evidence. RESULTS: A total of 74,132 patients from 12 observational studies were analyzed. Compared to H2RAs, PPIs increased the risk of CDI by 38.6% (pooled odds ratio, 1.386; 95% confidence interval, 1.152 to 1.668; p=0.001; I²=42.81%). Subgroup analyses of the purpose of study medication use, study site, and study design confirmed the consistency of a greater CDI risk with PPIs than with H2RAs. The overall quality of evidence was rated as low. CONCLUSIONS: The use of PPIs for both the prevention and treatment of stress ulcers was associated with a 38.6% increased risk of hospital-acquired CDI occurrence compared to H2RA use.
Clostridium difficile* ; Clostridium* ; Histamine Antagonists ; Humans ; Nursing ; Odds Ratio ; Population Characteristics ; Proton Pump Inhibitors* ; Proton Pumps* ; Protons* ; Stomach Ulcer ; Ulcer*

Proton pump inhibitors (PPIs) are widely used in clinical practice from early 1990s for the treatment of acid- related diseases. PPIs are superior to histamine2-receptor antagonists or anticholinergic agents. These drugs have proven to be effective, safe and well-tolerated during the past two decades. This brief review presents the pharmacodynamics and pharmacokinetics of PPIs and presents clincal applications of the drugs in acid-related diseases.
Gastric Acid/*secretion ; Gastrointestinal Agents/pharmacokinetics/*pharmacology/therapeutic use ; Humans ; Proton Pumps/*antagonists & inhibitors

The development and introduction into clinical practice of proton pump inhibitors (PPIs) have influenced the management of acid-peptic disorders dramatically. PPIs inhibit the gastric hydrogen/potassium adenosine triphosphatase selectively and irreversibly which is the final step in acid secretion. PPIs are currently the most effective form of therapy in acid-peptic diseases. All PPIs are potent, effective and generally safe, but little different in equivalent doses. PPIs undergo hepatic metabolism by cytochrome P450 (CYP) system. Polymorphism of CYP2C19 influences the pharmacokinetics and pharmacodynamics of PPIs. Doses and dosing schemes of PPIs based on CYP2C19 genotype status is expected to increase the efficacy in clinical outcome. The major indication of PPIs are acid-related diseases such as peptic ulcers and their complications, gastroesophageal reflux diseases, Zollinger-Ellison syndrome and eradication of Helicobacter pylori with antibiotics and dyspepsia. The potency and cost-effectiveness of PPIs have extended their clinical uses. However, their widespread and long-term use may limit the therapeutic benefit between efficacy and clinical problems such as acid rebound hypersecretion, enhanced oxyntic gastritis, problems with carcinoids in rodents and long-term concern for gastric cancer development. Further studies are needed to minimize the side effects and to maximize the therapeutic effects of PPIs.
Animals ; Anti-Ulcer Agents/*therapeutic use ; Gastroesophageal Reflux/*drug therapy ; Helicobacter Infections/*drug therapy ; Humans ; Peptic Ulcer/*drug therapy ; Proton Pumps/*antagonists & inhibitors

Significant progress and new insights have been gained since Helicobacter pylori was found in 1982. Even with currently most effective treatment regimen, about 10-20% of patients will fail to obtain the eradication of H. pylori infection. This review will focus on the empirical treatment for H. pylori infection in Korea. Seven days triple therapy (proton pump inhibitor, amoxicillin and clarithromycin) has been the main first line therapy for H. pylori infection in Korea after the recommendation by Korean H. pylori study group in 1998. Such triple therapy has been the effective regimen for eradication of H. pylori infection. However, the efficacy of 7 days proton pump inhibitor-amoxicillin-clarithromycin therapy becomes lower and various eradication rates probably reflects the increase in antimicrobial resistance, recently. The recent multi-center prospective randomized study and meta- analysis showed 14 days proton pump inhibitor-amoxicillin-clarithromycin therapy is more effective than 7 days or 10 days therapy. In the case of failure, quadruple therapy (proton pump inhibitor, a bismuth salt, metronidazole and tetracycline) is a very effective second-line regimen. After the failure of two or more eradication treatments, bacterial resistance to antibiotics should be evaluated and the regimen of third-line therapy should be selected according to each antimicrobial susceptibility. The empirical third-line therapies, recommended in the cases that antimicrobial susceptibility test is unavailable, are unclear of its validity at present in Korea. The triple therapies including rifabutin, moxifloxacin, or levofloxacin or dual therapy including high dose proton pump inhibitor and amoxicillin are needed to be proven as possible candidates for the empirical third-line therapy. Multiple eradication failures should be handled on a case-by-case basis by specialists.
Anti-Bacterial Agents/therapeutic use ; Anti-Ulcer Agents/therapeutic use ; Drug Therapy, Combination ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Proton Pumps/*antagonists & inhibitors

BACKGROUND/AIMS: Proton-pump inhibitor (PPI)-based triple therapy for Helicobacter pylori eradication is widely used with considerable failure rate. Bismuth-based, second-line therapy is also associated with failures in more than 20% of cases in Korea. Our aim was to evaluate the efficacy and tolerability of third-line therapy containing moxifloxacin as a rescue in Korea. METHODS: The subjects consisted of 201 patients infected with H. pylori, who were treated with PPI-based therapy, 42 patients treated with bismuth-based after failure of initial PPI triple therapy, and 10 patients treated with moxifloxacin-containing triple therapy after failure of successive initial and second-line therapy. Eradication rate, compliance and side effect rates were compared. RESULTS: The eradication rates of initial, second-line, and third-line therapy were as follows: 67.2%/83.3%, 54.8%/76.7%, 80.0%/88.9% by intention-to-treat and per protocol analysis, respectively. The compliance of patients for each treatment was 98.2%, 90.9%, 100%, respectively. The side effect rate was significantly higher in the bismuth triple therapy than in the PPI- or moxifloxacin-containing triple therapy (p<0.05). CONCLUSIONS: Moxifloxacin-containing triple therapy shows high eradication rate with fewer side effects and good compliance. Thus, this regimen could be used as a rescue therapy.
Adult ; Aged ; Antacids/administration & dosage ; Anti-Bacterial Agents/administration & dosage ; Aza Compounds/*administration & dosage ; Bismuth/administration & dosage ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Proton Pumps/antagonists & inhibitors ; Quinolines/*administration & dosage

BACKGROUND/AIMS: Quadruple therapy can be considered as a first-line therapy in areas where the resistance rate to clarithromycin is high. Comparison study of triple therapy and quadruple therapy for Helicobacter pylori (H. pylori) eradication is still lacking in Korea despite the increasing prevalence of antibiotic resistance. This study was conducted to compare the efficacy of triple and quadruple therapy as a first-line treatment in H. pylori infected patients with peptic ulcer. METHODS: Consecutive 149 cases of peptic ulcer disease associated with H. pylori infection were randomized either to proton pump inhibitor (PPI, bid), amoxicillin (1,000 mg, bid), and clarithromycin (500 mg, bid) (PAC group) or to PPI (bid), bismuth subcitrate (300 mg, qid), metronidazole (500 mg, tid), and tetracycline (500 mg, qid) (PBMT group) eradication treatments for 7 days. Outcome of eradication therapy was assessed by 13C-urea breath test performed 4-6 weeks after eradication. RESULTS: Eradication rates in PAC and PBMT group were 78.7% (59/75) and 71.6% (53/74) by intention to treat analysis, respectively (p=0.424). By per protocol analysis, eradication rates of PAC and PBMT group were 85.5% (59/69) and 85.5% (53/62), respectively (p=1.012). Adverse reactions occurred in 5 (6.6%) and 7 (9.5%) patients in PAC and PBMT group, respectively (p=0.346). CONCLUSIONS: One week-quadruple therapy as a first-line treatment for H. pylori infection does not offer any advantage over PPI-based triple therapy in Korean patients.
Adolescent ; Adult ; Aged ; Antacids/administration & dosage ; Anti-Infective Agents/administration & dosage ; Drug Therapy, Combination ; English Abstract ; Female ; Helicobacter Infections/complications/*drug therapy/microbiology ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Peptic Ulcer/microbiology ; Proton Pumps/antagonists & inhibitors

BACKGROUND/AIMS: At present, triple therapy schemes are recommended by national and international consensus conferences for the treatment of Helicobacter pylori (H. pylori) infection. However, even with the most effective current treatment regimens, about 10-20% of patients fail to eradicate H. pylori, necessitating alternative strategy to eradicate H. pylori in primary treatment failure. Therefore, we performed this study to evaluate the efficacy of quadruple therapy and to compare 1 and 2-week quadruple regimen as a second-line therapy. METHODS: The hospital records of 155 patients who failed to the standard triple therapy (proton pump inhibitor, amoxicillin, clarithromycin) were reviewed retrospectively, and divided the 1 or 2 weeks OBMT regimen (omeprazole 20 mg bid, bismuth salt 120 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid). Presence of H. pylori infection and side-effects of the treatment regimen were assessed 4 weeks after the cessation of treatment. CONCLUSIONS: One hundred and eight male and 47 female (mean age, 52.2+/-15.4) patients were enrolled. The overall eradication rate of H. pylori with quadruple therapy was 83.9% and the eradication rate was similar between 1 and 2 weeks of OBMT regimen (76.8% in OBMT 1 week, 87.9% in OBMT 2 weeks, respectively p=0.110). CONCLUSIONS: Quadruple therapy is an effective salvage regimen for H. pylori eradication after the failure of standard triple therapy. One week quadruple therapy is not significantly different from 2-weeks regimen as the second-line option for H. pylori eradication.
Adult ; Aged ; Anti-Bacterial Agents/administration & dosage ; Anti-Ulcer Agents/administration & dosage ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Proton Pumps/antagonists & inhibitors

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) is an important cause of various gastrointestinal diseases. H. pylori eradication is essential for the cure and prevention of associated diseases. Nowdays, proton pump inhibitor (PPI)-based triple therapy is the standard eradication regimen. The aims of this study were to compare the H. pylori eradication rate of different PPI-based triple therapies and to find out the factors influencing the eradication rate. METHODS: From May 2002 through Febraury 2004, H. pylori infected patients were treated with the eradication regimen based on one of the four PPIs (omeprazole, rabeprazole, esomeprazole and lansoprazole) for 1 or 2 weeks. After two weeks, drug compliance, adverse effects, and smoking history during the eradication therapy were obtained. The follow-up H. pylori test was performed 4 weeks after the completion of therapy. The data were analyzed by Chi-square test and multiple logistic regression analysis. RESULTS: Overall eradication rate was 83.5%. There was no significant difference in eradication rate among four PPIs (p=0.379). Odds ratio (OR) for omeprazole and rabeprazole was 1.15 (95% CI 0.50-2.68); for omeprazole and esomeprazole, OR 1.63 (95% CI 0.68-3.89); and for omeprazole and lansoprazole, OR 1.13 (95% CI 0.50-2.56). Smoking habit, site of ulcer, and the duration of therapy affected the eradication rate significantly. CONCLUSIONS: The efficacy of four different PPIs for H. pylori eradication is similar to each other. Smoking, site of ulcer, and the duration of treatment have significant effects on eradication rates.
Adult ; Anti-Infective Agents/*therapeutic use ; Anti-Ulcer Agents/*therapeutic use ; Comparative Study ; Drug Therapy, Combination ; English Abstract ; Female ; Helicobacter Infections/*drug therapy/microbiology ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Proton Pumps/*antagonists & inhibitors

BACKGROUND/AIMS: This study was done to evaluate the efficacy of rabeprazole (proton-pump-inhibitor) and ranitidine (H2-receptor antagonist) in the symptom relief and treatment of erosive esophagitis diagnosed by endoscopy. METHODS: A total of 110 patients with typical gastroesophageal reflux disease (GERD) symptoms were enrolled in this multicenter study. They were randomized into rabeprazole group (53 patients) and ranitidine group (57 patients) respectively. The patients in rabeprazole group were given 10 mg of rabeprazole and ranitidine group received 300 mg of ranitidine before breakfast and dinner for 8 weeks. After the end of treatment, we evaluated the endoscopic healing rate of reflux esophagitis and symptomatic improvement. RESULTS: After 8 weeks of treatment, rabeprazole group showed significantly higher complete endoscopic cure rate than ranitidine group (86.8% [46/53] vs. 57.9% [33/57], p=0.001) and higher symptomatic improvement of heartburn (91.2% [31/34] vs. 76.2% [32/42], p=0.085), especially in the first 7 days (76.7% vs. 45.3%, p=0.008). Also, rabeprazole group showed significantly higher improvement of regurgitation symptom than ranitidine group (100% [35/35] vs. 83% [39/47], p=0.009). Both group showed no differences in the improvement of chest pain and globus sensation. All the adverse events (rabeprazole group 4 events vs. ranitidine group 3 events) were mild and there was no abnormality in laboratory test. CONCLUSIONS: In patients with GERD, rabeprazole 10 mg b.i.d. is superior to ranitidine 300 mg b.i.d. in healing of reflux esophagitis and resolving typical GERD symptoms. Rabeprazole is an effective and well-tolerated drug for GERD treatment.
2-Pyridinylmethylsulfinylbenzimidazoles ; Adult ; Anti-Ulcer Agents/*therapeutic use ; Benzimidazoles/*therapeutic use ; Esophagitis, Peptic/*drug therapy ; Female ; Histamine H2 Antagonists/*therapeutic use ; Humans ; Male ; Middle Aged ; Omeprazole/*analogs & derivatives/therapeutic use ; Proton Pumps/*antagonists & inhibitors ; Proton-Translocating ATPases/therapeutic use ; Ranitidine/*therapeutic use

We describe a 58-year-old woman who was incidentally found to have gastric and colonic polyposis, hypoalbuminemia, cutaneous hyperpigmentation and onychodystrophy (Cronkhite-Canada syndrome). Histology of polyps from the stomach showed features of juvenile or retention type (hamartomatous) polyps with Helicobacter pylori (H. pylori) infection. The large pedunculated colonic polyps showed hamartomatous polyps with adenomatous component and polypectomy was performed. After the treatment with H. pylori eradication and omeprazole, the gastric polyposis, hypoalbuminemia and anemia regressed, and endoscopic polypectomy of gastric polyps were performed. After the continuous use of omeprazole for 14 months, the patient showed complete resolution of clinical features of Cronkhite-Canada syndome. The experience of this case suggests that eradication of H. pylori and proton pump inhibitor treatment might be considered in patients with gastric polyposis combined with Cronkhite-Canada syndome.
Anti-Ulcer Agents/*therapeutic use ; Colonic Polyps/complications/microbiology/pathology ; Female ; Helicobacter Infections/complications/*drug therapy ; *Helicobacter pylori ; Humans ; Hyperpigmentation/pathology ; Middle Aged ; Nails, Malformed/pathology ; Omeprazole/*therapeutic use ; Polyps/*complications/microbiology/pathology ; Proton Pumps/antagonists & inhibitors ; Stomach Neoplasms/*complications/microbiology/pathology ; Syndrome