OBJECTIVEHelicobacter pylori (H. pylori) eradication remains a challenge with increasing antibiotic resistance. Hybrid therapy has attracted widespread attention because of initial report with good efficacy and safety. However, many issues on hybrid therapy are still unclear such as the eradication efficacy, safety, compliance, influencing factors, correlation with antibiotic resistance, and comparison with other regimens. Therefore, a comprehensive review on the evidence of hybrid therapy for H. pylori infection was conducted.

DATA SOURCESThe data used in this review were mainly from PubMed articles published in English up to September 30, 2015, searching by the terms of "Helicobacter pylori" or "H. pylori", and "hybrid".

STUDY SELECTIONClinical research articles were selected mainly according to their level of relevance to this topic.

RESULTSTotally, 1871 patients of 12 studies received hybrid therapy. The eradication rates were 77.6-97.4% in intention-to-treat and 82.6-99.1% in per-protocol analyses. Compliance was 93.3-100.0%, overall adverse effects rate was 14.5-67.5%, and discontinued medication rate due to adverse effects was 0-6.7%. H. pylori culture and sensitivity test were performed only in 13.3% patients. Pooled analysis showed that the eradication rates with dual clarithromycin and metronidazole susceptible, isolated metronidazole or clarithromycin resistance, and dual clarithromycin and metronidazole resistance were 98.5%, 97.6%, 92.9%, and 80.0%, respectively. Overall, the efficacy, compliance, and safety of hybrid therapy were similar with sequential or concomitant therapy. However, hybrid therapy might be superior to sequential therapy in Asians.

CONCLUSIONSHybrid therapy showed wide differences in the efficacy but consistently good compliance and safety across different regions. Dual clarithromycin and metronidazole resistance were the key factor to efficacy. Hybrid therapy was similar to sequential or concomitant therapy in the efficacy, safety, and compliance.

Clarithromycin ; administration & dosage ; adverse effects ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Helicobacter pylori ; drug effects ; Humans ; Medication Adherence ; Metronidazole ; administration & dosage ; adverse effects ; Proton Pump Inhibitors ; administration & dosage

BACKGROUND/AIMS: We can expect to reduce costs and decrease adverse events by using low-dose triple therapy for H. pylori eradication. However, the efficacy of low-dose triple therapy for Koreans is questionable. In this study, we compared the efficacy of low-dose triple therapy with standard-dose triple therapy. METHODS: We enrolled 480 patients who were diagnosed as suffering with H. pylori infection via endoscopy with biopsy or CLO testing. Thirty patients were excluded due to malignancy or having undergone previous antibiotics medication. Two hundred and eighty patients received standard-dose triple therapy (pantoprazole 40 mg b.d, amoxicillin 1,000 mg b.d., and clarithromycin 500 mg b.d.), and 170 patients received low-dose triple therapy (pantoprazole 40 mg b.d., amoxicillin 750 mg b.d., and clarithromycin 250 mg b.d.). Eradication was evaluated 4~6 weeks after administering the medication. RESULTS: The H. pylori eradication rate was 77.9% in the standard-dose group, and 74.7% in the low-dose group. There was no significant difference in the H. pylori eradication rate between the two groups (p=0.444). The adverse events were significantly more frequent in the standard-dose group. One patient each in both groups discontinued medication because of an adverse event. CONCLUSIONS: The efficacy of low-dose therapy is similar to standard-dose therapy, and the adverse events are less frequent with low-dose therapy. This suggests that low-dose therapy would be preferred when considering the cost- benefit and low rate of adverse drug events.
Amoxicillin ; Anti-Bacterial Agents ; Biopsy ; Clarithromycin ; Drug-Related Side Effects and Adverse Reactions ; Endoscopy ; Helicobacter pylori* ; Helicobacter* ; Humans

The efficacy and safety of clarithromycin, roxithromycin and erythromycin stearate in mild pneumonia were compared in an open randomized trial. Eighty-six male patients, doing their obligatory military service, ranging between 19 and 24 years of age (mean 20), were randomly treated: 29 with clarithromycin 500 mg 12-hourly, 30 with roxithromycin 150 mg 12-hourly, and 27 with erythromycin stearate 500 mg 6-hourly, each course being administered for 10 days. Seventy-eight patients were able to be evaluated for efficacy, 28 receiving clarithromycin, 28 roxithromycin, and 22 erythromycin stearate. There were no significant differences among the groups in terms of clinical success rates (clinical cure or improvement: 89% for clarithromycin, 82% for roxithromycin, and 73% for erythromycin stearate, p = 0.32). However, we found that there were significant differences among the groups in terms of clinical cure rates (75% for clarithromycin, 64% for roxithromycin, and 41% for erythromycin stearate, p = 0.04). Adverse events, mostly gastrointestinal, caused discontinuation of treatment in 3.4% of the patients in the clarithromycin group, in 6.6% of the patients in the roxithromycin group, and in 18.5% of the patients in the erythromycin stearate group. The results indicate that there were no statistically significant differences among the three treatment groups in terms of clinical success rates, but that clarithromycin and roxithromycin were better tolerated.
Adult ; Antibiotics, Macrolide/therapeutic use* ; Antibiotics, Macrolide/adverse effects ; Clarithromycin/therapeutic use* ; Clarithromycin/adverse effects ; Comparative Study ; Erythromycin/therapeutic use* ; Erythromycin/analogs & derivatives* ; Erythromycin/adverse effects ; Female ; Human ; Male ; Pneumonia/radiography ; Pneumonia/physiopathology* ; Pneumonia/microbiology ; Pneumonia/drug therapy* ; Radiography, Thoracic ; Roxithromycin/therapeutic use* ; Roxithromycin/adverse effects

BACKGROUNDThe emergence of bacterial resistance to commonly used antibiotics, such as macrolides, is complicating the management of respiratory tract infections (RTIs). Telithromycin, a ketolide antimicrobial structurally related to macrolides, is approved for the treatment of community-acquired RTIs, and shows lower pathogen resistance rates. The purpose of this study was to compare the efficacy and safety of telithromycin with clarithromycin, a macrolide routinely used as therapy for RTIs.

METHODSWe performed a meta-analysis of relevant randomized-controlled trials (RCTs) identified in PubMed, the Cochrane Library, Embase, CNKI and VIP databases. The primary efficacy outcome was clinical treatment success assessed at the test-of-cure time in the per-protocol population, and the primary safety outcome was drug related adverse effects.

RESULTSSeven RCTs, involving 2845 patients with RTIs, were included in the meta-analysis. Oral telithromycin and clarithromycin showed a similar clinical treatment success in modified intention to treat and per-protocol population (cure and improvement) (odds ratios (ORs): 0.84, 95% confidence intervals (CI): 0.64 - 1.11 and OR: 1.14, 95%CI: 0.71 - 1.85, respectively). Similar findings were obtained for secondary efficacy outcomes: clinical treatment success at a late post-therapy visit (OR: 0.92, 95%CI: 0.57 - 1.48) and microbiological treatment success at the test-of-cure time (OR: 1.14; 95%CI: 0.71 - 1.85). The safety outcome analysis indicated telithromycin had a similar risk of drug-related adverse effect and serious adverse effect with clarithromycin.

CONCLUSIONSOur findings indicate that oral telithromycin and clarithromycin have similar treatment efficacy and adverse effect. The advantages of lower antimicrobial resistance rates, once-daily short-duration dosing and reported lower health-care costs make oral telithromycin a useful option for the empiric management of mild-to-moderate RTIs.

Anti-Bacterial Agents ; therapeutic use ; Clarithromycin ; adverse effects ; therapeutic use ; Community-Acquired Infections ; drug therapy ; Humans ; Ketolides ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Respiratory Tract Infections ; drug therapy

AIMTo prepare clarithromycin emulsion and investigate its pharmacokinetics in rats. And to do irritation test of the emulsion.

METHODSHigh pressure homogenization method was used to prepare clarithromycin emulsion, and the Nicomp380 machine was used to test the mean particle size and zeta-potential of clarithromycin emulsion. Irritation of emulsion was also evaluated compared with the positive control of clarithromycin solution using rat paw lick test and rabbit ear vein irritation test. Microbiological assay method was used for determining the drug concentration in plasma. Pharmacokinetics of two dosage forms in rats was also studied.

RESULTSThe mean particle size and zeta potential of clarithromycin emulsion were 156 nm and -31.8 mV, respectively. The emulsion was stable during the storage time at 4 degrees C for 6 month. The pain caused by emulsion reduced significantly compared with that of clarithromycin solution based on the results of rat paw lick test and rabbit ear vein test. The drug concentration-time curves of clarithromycin emulsion and clarithromycin solution were similar and could be described by two compartment model. AUC(0-1) of clarithromycin emulsion and clarithromycin solution were (66.76 +/- 16.34) and (59.00 +/- 11.20) microg x h x mL(-1), respectively.

CONCLUSIONStable emulsion could be prepared using high pressure homogenization method, and irritation caused by i.v. injection could be reduced significantly by using clarithromycin emulsion.

Animals ; Anti-Bacterial Agents ; administration & dosage ; adverse effects ; pharmacokinetics ; Area Under Curve ; Clarithromycin ; adverse effects ; blood ; pharmacokinetics ; Drug Compounding ; methods ; Emulsions ; Female ; Injections ; Male ; Pain ; chemically induced ; Pain Measurement ; methods ; Particle Size ; Rabbits ; Rats ; Rats, Wistar ; Solutions

OBJECTIVETo evaluate the clinical effect of a 10-day sequential therapy which was made up of omeprazole, clarithromycin, amoxicillin-clavulanate and metronidazole for the eradication of Helicobacter pylori (Hp) infection in children.

METHODA total of 214 children with abdominal pain, who were confirmed to have Hp infection through endoscopy, biopsy, and Hp culture. The 214 cases were randomly divided into four groups. A 10-day sequential therapy group accepted omeprazole 0.8 - 1.0 mg/(kg·d) plus amoxicillin-clavulanate 50 mg/(kg·d) for five days and omeprazole 0.8 - 1.0 mg/(kg·d), clarithromycin 20 mg/(kg·d) and metronidazole 20 mg/(kg·d) for the remaining five days. The 7-day triple therapy group, 10-day triple therapy group and 14-day triple therapy group received omeprazole 0.8 - 1.0 mg/(kg·d), amoxicillin-clavulanate 50 mg/(kg·d) and clarithromycin 20 mg/(kg·d) for 7 days,10 days,14 days, respectively. All drugs were given twice daily. All these patients received (13)C urea breath test ((13)C-UBT) four weeks after the treatment.

RESULTFinally, 199 patients were followed up, and the total rate of loss to follow-up was 7.0% (15/214). Hp eradication rate was 85.2% and 90.2% in the 10-day sequential therapy group on intention to treat (ITT) and per protocol (PP) analyses, 66.0% and 71.4% in the 7-day triple therapy group on ITT and PP analyses; 60.0% and 67.3% in 10-day triple therapy group on ITT and PP analyses, and 78.8% and 82.0% in patients who received the 10-day sequential regimen on ITT and PP analyses, respectively. By ITT analysis, there was significantly difference between the 10-day sequential therapy group and 7-day or 10-day triple therapy group (P < 0.05), while no significant difference was found between the 10-day sequential therapy group and 14-day triple therapy group (P > 0.05). The results of the ITT analysis and the PP analysis were the same. The four groups had neither significant difference in abdominal pain relief (P > 0.05) nor in incidence of adverse reactions (P > 0.05).

CONCLUSIONThe 10-day sequential regimen was significantly more effective than both 7-day triple regimen and 10-day triple regimen, while had the same eradication rate compared with the 14-day sequential therapy. But 10-day triple regimen to eradicate Hp infection in children had the advantages such as short course of treatment and better compliance.

Administration, Oral ; Adolescent ; Amoxicillin ; administration & dosage ; adverse effects ; Anti-Bacterial Agents ; administration & dosage ; adverse effects ; Anti-Ulcer Agents ; administration & dosage ; Breath Tests ; methods ; Child ; Child, Preschool ; Clarithromycin ; administration & dosage ; adverse effects ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Helicobacter Infections ; drug therapy ; Helicobacter pylori ; drug effects ; isolation & purification ; Humans ; Male ; Metronidazole ; administration & dosage ; adverse effects ; Microbial Sensitivity Tests ; Omeprazole ; administration & dosage ; adverse effects ; Time Factors ; Treatment Outcome

BACKGROUND/AIMS: The frequency of nontuberculous mycobacteria pulmonary disease in HIV-negative patients is increasing; the most common pathogen in Korea is the Mycobacterium avium complex (MAC). However, few studies have evaluated the treatment outcome of MAC pulmonary disease in Korea. METHODS: The efficacy of a clarithromycin-containing regimen for MAC pulmonary disease was studied in 42 patients treated for more than 6 months between January 2005 and December 2008. All patients were treated with a regimen consisting of clarithromycin, rifampin, and ethambutol. Streptomycin was added in 10 patients. RESULTS: Among the 42 patients, a negative culture conversion was achieved in 33 (78.6%), and the median duration of treatment in these patients was 19 months (interquartile range [IQR], 16 to 22). Of the 33 patients with a negative culture conversion, 14 completed treatment. During the follow-up period (median, 10 months; IQR, 4 to 20) for the 14 patients, one relapsed at 24 months after treatment completion. The culture conversion rate was significantly higher in patients who were treated with more than 500 mg/day clarithromycin (87.1% vs. 54.5%, p = 0.038). CONCLUSIONS: The combined regimen including clarithromycin was effective against MAC pulmonary disease. High-dose clarithromycin of more than 500 mg/day may improve the outcome of patients with MAC pulmonary disease.
Aged ; Anti-Bacterial Agents/*administration & dosage ; Clarithromycin/*administration & dosage/adverse effects ; Drug Therapy, Combination ; Female ; Humans ; Lung Diseases/*drug therapy ; Male ; Middle Aged ; Mycobacterium avium-intracellulare Infection/*drug therapy ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo study the efficacy of esomeprazole-based 1 week or 2 weeks triple therapy for Helicobactor pylori (H. pylori) infection in children.

METHODSOne hundred and five children with H. pylori infection identified by 13C-UBT were randomly assigned into Group A (n=60) and Group B (n=45). The patients of the two groups were administered with 1 week or 2 weeks triple therapy consisting of esomeprazole, clarithromycin and amoxillin, respectively. They were followed up four weeks after drug withdrawal.

RESULTSRecurrent abdominal pain was relieved in all of patients. Fifty-five patients (91.7%) showed 13C-UBT negative in Group A and 42 (93.3%) presented negative in Group B. There was no significant difference in the eradication rate of H. pylori.

CONCLUSIONSEsomeprazole-based triple therapy for H. pylori infection is effective in children. The efficacy of esomeprazole-based 1 week or 2 weeks triple therapy for this disorder does not appear to be different.

Adolescent ; Amoxicillin ; administration & dosage ; Anti-Bacterial Agents ; adverse effects ; Anti-Ulcer Agents ; administration & dosage ; Child ; Child, Preschool ; Clarithromycin ; administration & dosage ; Drug Therapy, Combination ; Esomeprazole ; administration & dosage ; Female ; Helicobacter Infections ; drug therapy ; Helicobacter pylori ; Humans ; Male

BACKGROUND/AIMS: Trends in successful eradication of Helicobacter pylori using first-line triple therapy, consisting of a proton pump inhibitor, amoxicillin, and clarithromycin, have been understudied. We evaluated H. pylori eradication rates at a single center over the last 10 years and identified risk factors related to eradication failure. METHODS: This study included 1,413 patients who were diagnosed with H. pylori infection and received 7 days of triple therapy between January 2003 and December 2012. We investigated H. pylori eradication rates retrospectively with respect to the year of therapy, as well as demographic and clinical factors. H. pylori eradication was confirmed by a 13C-urea breath test or a rapid urease test at least 4 weeks after the completion of triple therapy. RESULTS: The overall H. pylori eradication rate was 84.9%. Annual eradication rates from 2003 to 2012 were 93.5%, 80.0%, 87.2%, 88.5%, 92.0%, 88.3%, 85.7%, 84.1%, 83.7%, and 78.8%, respectively, by per-protocol analysis. The eradication rate with first-line triple therapy decreased during the last 10 years (p = 0.015). Multivariate analysis showed that female gender (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.12 to 2.55) and smoking (OR, 1.61; 95% CI, 1.05 to 2.47) were associated with the failure of H. pylori eradication therapy. CONCLUSIONS: The efficacy of first-line triple therapy for H. pylori infection has decreased over the last 10 years, suggesting an increase in antibiotic-resistant H. pylori strains. Thus, other first-line therapies may be necessary for H. pylori eradication in the near future.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amoxicillin/therapeutic use ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Breath Tests ; Chi-Square Distribution ; Clarithromycin/therapeutic use ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Female ; Helicobacter Infections/diagnosis/*drug therapy/microbiology ; Helicobacter pylori/*drug effects ; Humans ; Linear Models ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Proton Pump Inhibitors/adverse effects/*therapeutic use ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Sex Factors ; Smoking/adverse effects ; Time Factors ; Treatment Failure ; Young Adult

BACKGROUND/AIMS: Antibiotic resistance of Helicobacter pylori (H. pylori) is a significant clinical problem because it reduces the efficacy of eradication therapy. The aims of this study were to assess the changing patterns of antibiotic resistance of H. pylori in patients with peptic ulcer diseases and to evaluate the eradication rate in antibiotic resistant H. pylori strains. METHODS: One hundred forty four H. pylori isolates obtained from 466 patients with peptic ulcer disease between June 2001 and December 2005 were examined for antimicrobial resistance. The minimum inhibitory concentration (MIC) of metronidazole was determined by modified broth microdilution method (mBMD) and E test. MICs of clarithromycin and amoxicillin were determined by mBMD, E test, and disc diffusion test. The breakpoints for metronidazole, clarithromycin, and amoxicillin resistance were defined as >8microgram/mL, >1microgram/mL, and > or =1microgram/mL, respectively. RESULTS: Resistance to metronidazole and clarithromycin was detected in 34.7% and 16.7% of H. pylori isolates, respectively. During the recent 5-year study period, amoxicillin-resistant rate of H. pylori was 11.8%, and multi-drug resistance rate of H. pylori was 16.7%. The eradication rate of clarithromycin containing triple therapies was low (7.8%) in clarithromycin-resistant H. pylori strains. CONCLUSIONS: The proportions of clarithromycin-resistant H. pylori strains have increased significantly over the last 5-years. There is an increasing tendency for the emergence of strains with multi-drug resistance. The increase in clarithromycin-resistant strains results in a decrease in eradication rate for H. pylori. In areas with high clarithromycin resistance, new alternative first-line treatment combination should be considered.
Adult ; Aged ; Amoxicillin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Clarithromycin/adverse effects/therapeutic use ; Disk Diffusion Antimicrobial Tests ; *Drug Resistance, Bacterial ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy/microbiology ; Helicobacter pylori/*drug effects/isolation & purification ; Humans ; Male ; Metronidazole/therapeutic use ; Microbial Sensitivity Tests ; Middle Aged ; Peptic Ulcer/*drug therapy ; Retrospective Studies