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

Pseudomembranous colitis (PMC) is a frequent cause of morbidity and mortality among hospitalized patients. Although diarrhea is the most common manifestation, PMC may be associated with intraperitoneal fluid accumulation in the severe cases. And a few cases showing both ascites and pleural effusion have been reported in patients with PMC. We report a case of PMC who showed elevated serum and ascites levels of carcinoembryonic antigen (CEA) with a normal CEA level in pleural effusion and who successfully recovered after oral administration of metronidazole. After treatment, the serum CEA level returned to the reference range.
Administration, Oral ; Ascites ; Carcinoembryonic Antigen* ; Diarrhea ; Enterocolitis, Pseudomembranous* ; Humans ; Metronidazole ; Mortality ; Pleural Effusion ; Reference Values

BACKGROUND/AIMS: Bismuth-containing quadruple and moxifloxacin-based triple regimens are recommended as second-line therapy for Helicobacter pylori infection. The aim of this study was to compare the efficacy of each regimen. METHODS: From August 2004 to October 2012, a total of 949 patients (mean age, 54.32+/-12.08 years; male, 49.4%) who failed H. pylori eradication with a standard triple regimen were included. Patients treated with a bismuth-containing quadruple regimen for 7 and 14 days were designated as 7-BMT and 14-BMT, respectively, and those treated with a moxifloxacin-based triple regimen for 7 and 14 days were designated as 7-MA and 14-MA, respectively. H. pylori eradication was confirmed using the 13C-urea breath test, rapid urease test or histology. RESULTS: The eradication rates by 7-BMT, 14-BMT, 7-MA, and 14-MA were 66.4% (290/437), 71.1% (113/159), 53.1% (51/96), and 73.5% (189/257), respectively, by intention-to-treat analysis (ITT) and 76.5% (284/371), 83.8% (109/130), 55.6% (50/90), and 80.6% (187/232), respectively, by per-protocol analysis (PP). The eradication rates were higher in 14-BMT than 7-BMT by the ITT and PP analyses (p=0.277 and p=0.082, respectively). The 14-BMT and 14-MA treatments showed similar efficacies by ITT and PP (p=0.583 and p=0.443, respectively). CONCLUSIONS: The 7-BMT, 14-BMT, and 14-MA treatments showed similar and suboptimal efficacies. In both regimens, extending the duration of treatment may be reasonable considering the high level of antibiotic resistance in Korea.
Adult ; Aged ; Amoxicillin/administration & dosage ; Antacids/*administration & dosage ; Anti-Infective Agents/*administration & dosage ; Bismuth/*administration & dosage ; Drug Administration Schedule ; Drug Therapy, Combination/methods ; Female ; Fluoroquinolones/*administration & dosage ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Intention to Treat Analysis ; Male ; Metronidazole/administration & dosage ; Middle Aged ; Proton Pump Inhibitors/administration & dosage ; Retrospective Studies ; Tetracycline/administration & dosage ; Treatment Outcome

BACKGROUND/AIMS: Because the efficacy of standard triple therapy for Helicobacter pylori eradication has declined, new regimens such as sequential therapy (ST) and concomitant therapy (CoCTx) have been introduced. The aim of this study was to compare the efficacy of 10-day ST and 10-day CoCTx for H. pylori eradication. METHODS: We retrospectively reviewed the medical records of 316 patients with proven H. pylori infection. They were assigned to one of 2 regimens; ST (n=191) consisted of, lansoprazole 30 mg and amoxicillin 1 g for 5 days followed by lansoprazole 30 mg, metronidazole 500 mg, and clarithromycin 500 mg for 5 days, and CoCTx (n=125) consisted of lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg for 10 days. All drugs were administered twice a day. Bacterial eradication was checked by using a 13C-urea breath test at least 4 weeks after completion of treatment. RESULTS: The mean age and male to female ratio was 51.74 and 1.03, respectively. Baseline characteristics were not different in both groups. Ten day CoCTx group (94.4%, 118/125) showed better eradication rate than ST group (82.2%, 157/191) (p=0.002). Drug compliances were not statistically different between the two groups (p=0.19). Side effects were more frequently reported in the CoCTx group than in the ST group (p=0.03). CONCLUSIONS: Ten-day CoCTx was superior to ST in terms of eradicating H. pylori infection. Although the CoCTx producing more side effects than ST, CoCTx can be thought to be a promising alternative to ST as a treatment regimen for H. pylori eradication.
Adult ; Aged ; Amoxicillin/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Breath Tests ; Clarithromycin/therapeutic use ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Helicobacter Infections/diagnosis/*drug therapy ; *Helicobacter pylori ; Humans ; Lansoprazole/therapeutic use ; Logistic Models ; Male ; Metronidazole/therapeutic use ; Middle Aged ; Proton Pump Inhibitors/*therapeutic use ; Retrospective Studies ; Risk Factors ; Treatment Outcome

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

The paper is to report the development of an optic-fiber sensing technology method to analyze metronidazole tablets rapidly. In this fiber-optic sensing system, the light from source delivering to probe can be dipped into simple-handling sample solution, absorbed by the solution and reflected to the fiber-optic and detected in the detection system at last. Then the drug content can be shown in the screen from the ultraviolet absorption spectra and the consistency between that obtained by this method and that in China Pharmacopoeia can be compared. With regard to data processing, a new method is explored to identify the authenticity of drugs using the similarity between the sample map and the standard pattern by full ultraviolet spectrum. The results indicate that ultraviolet spectra of tablets can be obtained from this technology and the determination results showed no significant difference as compared with the method in China Pharmacopoeia (P > 0.05), and the similarity can be a parameter to identify the authenticity of drugs.
Chemistry, Pharmaceutical ; Drug Contamination ; Fiber Optic Technology ; methods ; Metronidazole ; administration & dosage ; analysis ; Optical Fibers ; Solubility ; Spectrophotometry, Ultraviolet ; methods ; Tablets

BACKGROUNDBacterial vaginosis (BV) is one of the most common infectious diseases among sexually active women and is associated with the increased acquisition of a variety of sexually transmitted diseases. This study aimed to compare the efficacy of a non-antibiotic sucrose gel against an antibiotic metronidazole gel for the treatment of BV.

METHODSA randomized, double-blinded, multi-center, parallel-group, placebo-controlled phase III clinical trial was conducted at eight hospitals in China. A total of 560 subjects with clinically diagnosed BV were randomly assigned into three groups for vaginally receiving sucrose, metronidazole, and placebo gels, respectively, twice daily for five consecutive days. The efficacy of therapeutic cure, defined as an achievement of both microbiologic cure (a Nugent score of 3 or less) and clinical cure (a resolution of the clinical findings from the baseline visit), was evaluated at the 1st and 2nd test-of-cure (TOC) visits at 7-10 and 21-35 days after the start of treatment, respectively.

RESULTSTherapeutic cure rates for sucrose, metronidazole, and placebo gel groups were 83.13%, 71.30% and 0.92%, at the 1st TOC, and 61.04%, 66.67% and 7.34%, at the 2nd TOC, respectively. While there was no significant difference between the sucrose and metronidazole gel groups at the 2nd TOC (P = 0.305), and sucrose gel was more effective than metronidazole gel at the 1st TOC (P = 0.009).

CONCLUSIONThese findings suggest that sucrose gel restores normal vaginal flora more rapidly than metronidazole gel and can be used as a novel treatment for BV.

Administration, Intravaginal ; Adolescent ; Adult ; Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Metronidazole ; administration & dosage ; therapeutic use ; Middle Aged ; Sucrose ; administration & dosage ; therapeutic use ; Treatment Outcome ; Vaginosis, Bacterial ; drug therapy ; Young Adult

OBJECTIVETo compare the therapeutic effects of minocycline, metronidazole and iodine glycerin on periodontitis.

METHODSA total of 123 patients were randomly divided into 3 groups to receive the 3 topical remedies administered into the periodontal pockets. The total response rate of the 3 treatments was calculated, and the changes in GI, PL I, PD and BO P were observed.

RESULTSAll the clinical indices of the 3 groups showed obvious improvements after the treatments compared with the baseline levels. The clinical indices of minocycline group and metronidazole group showed significant greater improvements than those of iodine glycerin group. The total response rate in minocycline group and metronidazole group was higher than that of iodine glycerin group.

CONCLUSIONSMinocycline and metronidazole as topical remedies can be effective auxiliary treatments of periodontitis.

Administration, Topical ; Adult ; Aged ; Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Female ; Humans ; Iodine ; agonists ; therapeutic use ; Male ; Metronidazole ; administration & dosage ; therapeutic use ; Middle Aged ; Minocycline ; administration & dosage ; therapeutic use ; Periodontal Pocket ; Periodontitis ; drug therapy ; Young Adult

The aim of present study is to develop a pharmacokinetic model for microencapsulated metronidazole to predict drug absorption pattern in healthy human and validate this model internally. Metronidazole was microencapsulated into ethylcellulose shells followed by the conversion of these microcapsules into tablets. Dissolution study of tablets was conducted in 450 mL double distilled water, 0.1 mol L(-1) HCl and phosphate buffer (pH 6.8) maintained at (37+/-0.5) degrees C using USP apparatus II at 50, 100 and 150 r min(-1). Three metronidazole tablets (T1: fast release, T2: moderate release, T3: slow release and reference) were administered to twenty four healthy human volunteers and serial blood samples were collected for 12 hours followed by their analysis using RP-HPLC. Drug release data were analyzed by various model dependent and independent approaches. Drug absorbed (%) was determined by Wagner-Nelson method from plasma concentration profile. Internal predictability was checked from Cmax and AUC. Optimum dissolution profile was observed in double distilled water and 50 r min(-1). A good level A correlation was observed between drug dissolution and absorption profiles (correlation coefficient, R2 = 0.9009, 0.9426, 0.9015 and 0.932 for T1, T2, T3 and reference, respectively). Internal predictability was found less than 10%. Good correlation coefficients and low prediction errors elaborate the validity of this mathematical in-vitro in-vivo correlation model as a predictive tool for the determination of pharmacokinetics from dissolution data.
Chemistry, Pharmaceutical ; Drug Compounding ; Drug Design ; Humans ; Male ; Metronidazole ; administration & dosage ; pharmacokinetics ; Young Adult

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. Proton pump inhibitor (PPI)-based triple therapy is the most preferred regimen in clinical practice. However, a critical fall in the H. pylori eradication rate has been observed in the recent years. A novel 10 day-sequential therapy consists of five days of dual therapy followed by five days of triple therapy regimen has recently been described. We aimed to evaluate whether 10 day-sequential therapy eradicated H. pylori infection better than the PPI-based triple therapy in Korea. METHODS: 158 patients with proven H. pylori infection were randomized to receive either 10 day-sequential therapy (20 mg of omeprazole, 1.0 g of amoxicillin, each administered twice daily for the first 5 days, followed by 20 mg of omeprazole, 500 mg of clarithromycin, 500 mg of metronidazole, each administered twice daily for the remaining 5 days) or PPI-based triple therapy (20 mg of omeprazole, 1.0 g of amoxicillin, 500 mg of clarithromycin, each administered twice daily for 1 week). Outcome of eradication therapy was assessed 8 weeks after the cessation of treatment. RESULTS: Eradication rates of 10 day-sequential therapy and PPI-based triple therapy were 77.9% (60/77) and 71.6% (58/81) by intention to treat analysis, respectively (p=0.361). By per protocol analysis, eradication rates of 10 day-sequential therapy and triple therapy were 85.7% (60/70) and 76.6% (58/76), respectively (p=0.150). There were no significant differences in adverse event rates and treatment compliance between two groups. CONCLUSIONS: The 10 day-sequential therapy regimen failed to achieve significantly higher eradication rates than PPI-based triple therapy.
Adult ; Amoxicillin/administration & dosage ; Anti-Bacterial Agents/*administration & dosage ; Anti-Ulcer Agents/administration & dosage ; Data Interpretation, Statistical ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy/microbiology ; *Helicobacter pylori ; Humans ; Korea ; Male ; Metronidazole/administration & dosage ; Middle Aged ; Omeprazole/administration & dosage ; Time Factors ; Treatment Outcome