Sung-Shuo Kao

Randomized Controlled Trial Comparing 7-Day Triple, 10-Day Sequential, and 7-Day Concomitant Therapies for Helicobacter pylori Infection

ABSTRACT With the rising prevalence of antimicrobial resistance, the failure rate of the standard triple therapy for Helicobacter pylori infection is increasing. Sequential therapy and concomitant therapy have been recommended to replace standard triple therapy for H. pylori eradication in regions with high clarithromycin resistance. The aim of this prospective, randomized, and controlled study was to simultaneously assess the efficacies of 10-day sequential and 7-day concomitant therapies versus a 7-day standard triple therapy for treating H. pylori infection. Consecutive H. pylori-infected subjects were randomly assigned to a 7-day standard triple therapy (pantoprazole, clarithromycin, and amoxicillin for 7 days), a 10-day sequential therapy (pantoprazole and amoxicillin for 5 days, followed by pantoprazole, clarithromycin, and metronidazole for a further 5 days), or a 7-day quadruple therapy (pantoprazole, clarithromycin, amoxicillin, and metronidazole for 7 days). H. pylori status was confirmed 6 weeks after therapy. Three hundred seven H. pylori-infected participants were randomized to receive triple (n = 103), sequential (n = 102), or concomitant (n = 102) therapies. The eradication rates by an intention-to-treat analysis in the three treatment groups were 81.6% (95% confidence interval [CI], 74.1% to 89.0%), 89.2% (95% CI, 83.2% to 95.2%), and 94.1% (95% CI, 89.5% to 98.7%). The seven-day concomitant therapy had a higher eradication rate than did the 7-day triple therapy (difference, 12.5%; 95% CI, 3.7% to 21.3%). There were no significant differences in the eradication rates between the sequential and standard triple therapies. All three treatments exhibited similar frequencies of adverse events (8.7%, 8.8%, and 13.7%, respectively) and drug compliance (99.0%, 98.0%, and 100.0%, respectively). In conclusion, the seven-day concomitant therapy is superior to the 7-day standard triple therapy for H. pylori eradication. Additionally, it is less complex than the 10-day sequential therapy because the drugs are not changed halfway through the treatment course. (This study has been registered at ClinicalTrials.gov under registration no. NCT1769365.)

Ten‐Day Quadruple Therapy Comprising Proton‐Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin Achieves a High Eradication Rate for Helicobacter pylori Infection after Failure of Sequential Therapy

Sequential therapy has been recommended in the Maastricht IV/Florence Consensus Report as the first‐line treatment for Helicobacter pylori eradication in regions with high clarithromycin resistance. However, it fails in 5–24% of infected subjects, and the recommended levofloxacin‐containing triple rescue therapy only achieves a 77% eradication rate after failure of sequential therapy.

Reverse Sequential Therapy Achieves a Similar Eradication Rate as Standard Sequential Therapy for Helicobacter pylori Eradication: A Randomized Controlled Trial

Sequential therapy is a two‐step therapy achieving a promising eradication rate for Helicobacter pylori infection. The rationale of sequential method has been proposed that amoxicillin weakens bacterial cell walls in the initial phase of treatment, preventing the development of drug efflux channels for clarithromycin and metronidazole used in the second phase. The aim of this prospective, randomized, controlled study was to investigate whether the efficacy of reverse sequential therapy was noninferior to sequential therapy in the treatment of H. pylori infection.

A Randomized Controlled Study Comparing Reverse Hybrid Therapy and Standard Triple Therapy for Helicobacter pylori Infection

AbstractReverse hybrid therapy is an 1-step 2-phase treatment for Helicobacter pylori (H. pylori) infection with less cost than standard triple therapy. We conducted a randomized, controlled study to compare the efficacies of standard triple therapy and reverse hybrid therapy in the treatment of H. pylori infection.From October 2012 to March 2015, consecutive H. pylori-infected subjects were randomly allocated to receive either a reverse hybrid therapy (pantoprazole plus amoxicillin for 12 days and clarithromycin plus metronidazole for the initial 7 days) or a standard triple therapy (pantoprazole plus amoxicillin and clarithromycin for 12 days). H. pylori status was assessed 6 weeks after treatment. Additionally, antibiotic resistances and host CYP2C19 genotypes were examined and analyzed.A total of 440 H. pylori-infected patients were randomly assigned to receive either a reverse hybrid (n = 220) or a standard triple therapy (n = 220). The reverse hybrid group had a higher eradication rate than standard triple group either by intention-to-treat (93.6% vs. 86.8%; P = 0.016) or per-protocol analysis (95.7% vs. 88.3%; P = 0.005). The 2 patient groups exhibited similar frequencies of overall adverse events (14.1% vs. 9.5%) and drug compliance (96.8% vs. 98.6%). Clarithromycin resistance was an independent risk factor predicting eradication failure in standard triple group (P < 0.001), but not in reverse hybrid group. CYP2C19 genotypes did not affect the eradication rates in both groups.Reverse hybrid therapy can be considered for first-line treatment of H. pylori infection since the new therapy achieves a higher eradication rate than standard triple therapy with similar tolerability and less pharmaceutical cost.

Ten-Day Quadruple Therapy Comprising Proton Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin is More Effective than Standard Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori Infection: A Randomized Controlled Trial

Objectives:Proton pump inhibitor (PPI)–amoxicillin–fluoroquinolone triple therapy is recommended as a second-line treatment of Helicobacter pylori infection in the Maastricht V/Florence Consensus Report. However, the eradication rate of this standard salvage treatment is suboptimal. The objective of this study is to compare the efficacy of esomeprazole–bismuth–tetracycline–levofloxacin therapy (TL quadruple therapy) and esomeprazole–amoxicillin–levofloxacin triple therapy (AL triple therapy) in rescue treatment for H. pylori infection.Methods:Consecutive H. pylori-infected subjects after failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (esomeprazole 40 mg b.d., bismuth 120 mg q.d.s., tetracycline 500 mg q.d.s., and levofloxacin 500 mg o.d.) or AL triple therapy (esomeprazole 40 mg b.d., amoxicillin 500 mg q.d.s., and levofloxacin 500 mg o.d.) for 10 days. H. pylori status was assessed 6 weeks after the end of treatment.Results:The study was stopped after an interim analysis. Of 50 patients in the TL quadruple therapy, 49 (98.0%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved in 36 of 52 patients (69.2%) receiving AL triple therapy. Intention-to-treat analysis demonstrated that TL quadruple therapy achieved a markedly higher eradication rate than AL triple therapy (difference: 28.8%; 95% confidence interval: 15.7% to 41.9%; P<0.001). Per-protocol analysis yielded a similar result (97.8% vs. 68.6%; P<0.001). The two treatment groups exhibited comparable frequencies of overall adverse events (22.0% vs. 11.5%) and drug compliance (90.0% vs. 98.1%). The subgroup analysis showed that TL quadruple therapy was superior to AL triple therapy in patients with failure of either standard triple therapy (100% vs. 75.0%; P=0.010) or non-bismuth quadruple therapy (95.0% vs. 52.6%; P=0.003).Conclusions:Ten-day PPI–bismuth–tetracycline–levofloxacin quadruple therapy is a good option for rescue treatment of H. pylori infection following failure of standard triple or non-bismuth quadruple therapy.

Prevention of acute exacerbation of chronic hepatitis B infection in cancer patients receiving chemotherapy in a hepatitis B virus endemic area

Reactivation of hepatitis B viral (HBV) infection in cancer patients undergoing chemotherapy may cause interruption of chemotherapy and lead to liver failure and death. In our institute, a computerized order entry–based alert system was introduced in September 2011 to remind healthcare providers of HBV testing when prescribing chemotherapy. Since August 2012, an order entry–based therapeutic control system has been applied to ensure HBV prophylaxis during chemotherapy. This retrospective cohort study included cancer patients receiving chemotherapy in the Kaohsiung Veterans General Hospital from November 2009 to June 2013. The prechemotherapy HBV screening rate, HBV prophylactic rate, and severe HBV acute exacerbation rate were compared between stages with different order systems. Newly diagnosed cancer patients (n = 2512) were included. The HBV testing rate in the screening reminder stage was higher than that in the educational stage (93.5% versus 40.2%, P < 0.001), whereas the adequate HBV prophylactic rates in the two order entry–based stages were comparable (41.1% versus 39.2%). Patients in the order entry–based therapeutic control stage had a higher HBV screening rate (99.3% versus 40.2%, P < 0.001) and a higher HBV prophylactic rate (95.8% versus 39.2%, P < 0.001) than those in the educational stage. Additionally, the severe HBV acute exacerbation rate in the therapeutic control stage was lower than those in the educational and screening reminder stages (0% versus 1.2% and 1.2%, respectively; both P < 0.01). Conclusion: A computerized order entry–based therapeutic control system can provide excellent prechemotherapy HBV screening for cancer patients undergoing chemotherapy and can effectively prevent severe acute exacerbation of HBV infection in hospitals among HBV endemic areas. (Hepatology 2015;62:387–396

7-Day Nonbismuth-Containing Concomitant Therapy Achieves a High Eradication Rate for Helicobacter pylori in Taiwan.

Background. Ten-day concomitant therapy achieves a high eradication rate in Taiwan. Whether shortening the duration of concomitant therapy can still keep a high eradication rate remains unclear. Aim. To assess the eradication rate of 7-day pantoprazole-containing concomitant therapy in Taiwan and to investigate factors influencing the eradication outcome. Methods. From March 2008 to March 2012, 319 H. pylori-infected patients receiving a 7-day pantoprazole-containing concomitant regimen (pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 7 days) were included. Patients were asked to return at the second week to assess drug compliance and adverse effects. Repeated endoscopy or urea breath test was performed at 8 weeks after the end of eradication therapy. Results. The eradication rates according to intention-to-treat and per-protocol analyses were 93.7% (299/319) and 96.4% (297/308), respectively. Adverse events occurred in 13.2% (42/319) of the patients. The compliance rate was 98.4% (314/319). Multivariate analysis disclosed that poor compliance was the only independent factor influencing the efficacy of anti-H. pylori therapy with an odds ratio of 0.073 (95% confidence interval, 0.011–0.483). Conclusion. 7-day concomitant therapy achieved a very high eradication rate for H. pylori infection in Taiwan. Drug compliance was the only clinical factor influencing treatment efficacy.

Helicobacter pylori eradication with bismuth quadruple therapy leads to dysbiosis of gut microbiota with an increased relative abundance of Proteobacteria and decreased relative abundances of Bacteroidetes and Actinobacteria

Bismuth quadruple therapy is the treatment of choice for the first‐line therapy of Helicobacter pylori infection in areas of high clarithromycin resistance. Currently, the impact of the promising treatment on gut microbiota remains unclear.

A Randomized Controlled Trial Shows that both 14-Day Hybrid and Bismuth Quadruple Therapies Cure Most Patients with Helicobacter pylori Infection in Populations with Moderate Antibiotic Resistance

ABSTRACT Hybrid therapy is a novel two-step treatment achieving a high eradication rate for Helicobacter pylori infection. Currently, whether this new therapy achieves a higher eradication rate than bismuth quadruple therapy remains an unanswered question. The aim of this prospective, randomized comparative study was to investigate the efficacies of 14-day hybrid therapy and bismuth quadruple therapy in the treatment of H. pylori infection. From July 2013 to June 2015, eligible H. pylori-infected subjects were randomly assigned to receive either 14-day bismuth quadruple therapy (pantoprazole, bismuth subcitrate, tetracycline, and metronidazole for 14 days) or 14-day hybrid therapy (a 7-day dual therapy with pantoprazole plus amoxicillin, followed by a 7-day quadruple therapy with pantoprazole plus amoxicillin, clarithromycin, and metronidazole). H. pylori status was examined 6 weeks after the end of treatment. Three hundred thirty H. pylori-infected participants were randomized to receive 14-day bismuth quadruple therapy (n = 164) or 14-day hybrid therapy (n = 166). The eradication rates by intention-to-treat analysis were similar: 93.9% versus 92.8%, respectively (95% confidence interval [CI], −4.3% to 5.4%; P = 0.68). Per-protocol analysis yielded similar results (96.7% versus 94.9%, respectively; P = 0.44). However, bismuth quadruple therapy had a higher frequency of adverse events than hybrid therapy (55.5% versus 15.7%, respectively; 95% CI, 30.4% to 49.2%; P < 0.001). The two treatments exhibited comparable drug adherence (93.9% versus 97%, respectively). The resistance rates of antibiotics were: clarithromycin, 16.7% of patients; amoxicillin, 1.3%; metronidazole, 25%; and tetracycline, 0%. In the bismuth quadruple therapy group, the eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (70.0% versus 96.4%, respectively; P = 0.04). In the hybrid therapy group, no significant impact of clarithromycin or metronidazole resistance on eradication rates was identified. Both 14-day hybrid and bismuth quadruple therapies cure most patients with H. pylori infection in populations with moderate antibiotic resistance. However, the 14-day hybrid therapy has fewer adverse effects than the bismuth quadruple therapy. (This study has been registered at ClinicalTrials.gov under identifier NCT02541864.)

Is endoscopic treatment beneficial in patients with clinically suspicious of common bile duct stones but no obvious filling defects during the ERCP examination

BackgroundSometimes, no definite filling defect could be found by cholangiogram (ERC) during the endoscopic retrograde cholangio-pancreatiographic (ERCP) exam; even prior images had evidence of common bile duct stones (CBDS). We aimed in estimating the positive rate of extraction of CBDS who had treated by endoscopic sphincterotomy/endoscopic papillary balloon dilation (EST/EPBD) with negative ERC finding.MethodsOne hundred forty-one patients with clinically suspicious of CBDS but negative ERC, who had received EST/EPBD treatments was enrolled. Potential factors for predicting CBDS, as well as the treatment-related complications were analyzed.ResultsNearly half of the patients with negative ERC, had a positive stone extraction. Only patients with high probability of CBDS were significantly associated with positive stone extraction. Moreover, patients with intermediate probability of CBDS had higher rates of overall complications, including post-ERCP pancreatitis. In addition, no significant difference of post-ERCP pancreatitis was found between EST and EPBD groups in any one group of patients with the same probability of CBDS.ConclusionsRegarding patients with negative ERC, therapeutic ERCP is beneficial and safe for patients present with high probability of CBDS. Moreover, under the same probability of CBDS, there was no significance difference in post-ERCP pancreatitis between EST and EPBD.