Ming-Jong Bair

The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors—A Nationwide Study

Objective The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance. Methods The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method. Results The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000–2007 to 8.3% in 2008–2010 and 13.4% in 2011–2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance. Conclusions The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

Necrotizing fasciitis in southeast Taiwan: clinical features, microbiology, and prognosis

OBJECTIVES To determine the spectrum of microorganisms, clinical features, and risk factors of necrotizing fasciitis in southeast Taiwan. METHODS We retrospectively studied patients diagnosed with necrotizing fasciitis and fully treated in our hospital for the period January 1995 to December 2006. RESULTS The mean age of the patients was 58.2+/-14.2 years. The affected anatomical sites were primarily peripheral (91 patients, 85.8%). Sixty patients (56.6%) had a type 1 infection, 17 patients (16.0%) had type 2, and eight patients (7.5%) had type 3. Diabetes mellitus was the most common comorbidity. A single pathogen was identified as the infectious agent in 64 patients (60.4%), multiple pathogens were identified in 21 patients (19.8%), and no organism was identified in 21 patients (19.8%). Streptococcus pyogenes was the most common pathogen. The average hospital stay was 28.0+/-23.1 days. Patients received a mean of 2.3+/-1.2 debridements, and five patients (4.7%) eventually underwent an amputation. The overall mortality was 17.0%. Predictors of mortality included advanced age, class C liver cirrhosis, ascites, higher serum creatinine, and lower hemoglobin and platelet levels. CONCLUSIONS Monobacterial infections are more common in our patients. Accurate early diagnosis and extensive surgical debridement are essential for a favorable outcome.

Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients.

Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long‐term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB‐related cirrhosis patients.

Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial

BACKGROUND Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. METHODS In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive 13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879. FINDINGS Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6-92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7-88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4-86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7-10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. INTERPRETATION Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. FUNDING National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

Sequential therapy for 10 days versus triple therapy for 14 days in the eradication of Helicobacter pylori in the community and hospital populations: a randomised trial

Objective Significant heterogeneity was observed in previous trials that assessed the efficacies of sequential therapy for 10 days (S10) versus triple therapy for 14 days (T14) in the first-line treatment of Helicobacter pylori. We aimed to compare the efficacy of S10 and T14 and assess the factors affecting their efficacies. Design We conducted this open-label randomised multicentre trial in eight hospitals and one community in Taiwan. 1300 adult subjects with H pylori infection naïve to treatment were randomised (1:1) to receive S10 (lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, clarithromycin and metronidazole for another 5 days) or T14 (lansoprazole, amoxicillin and clarithromycin for 14 days). All drugs were given twice daily. Successful eradication was defined as negative 13C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. Results The eradication rates of S10 and T14 were 87.2% (567/650, 95% CI 84.4% to 89.6%) and 85.7% (557/650, 95% CI 82.8% to 88.2%) in the ITT analysis, respectively, and were 91.6% (556/607, 95% CI 89.1% to 93.4%) and 91.0% (548/602, 95% CI 88.5% to 93.1%) in the PP analysis, respectively. There were no differences in compliance or adverse effects. The eradication rates in strains susceptible and resistant to clarithromycin were 90.7% and 62.2%, respectively, for S10, and were 91.5% and 44.4%, respectively, for T14. The efficacy of T14, but not S10, was affected by CYP2C19 polymorphism. Conclusions S10 was not superior to T14 in areas with low clarithromycin resistance. Trial registration number NCT01607918.

Rabeprazole- versus Esomeprazole-Based Eradication Regimens for H. pylori Infection

Background:  Different kinds of proton pump inhibitor‐based triple therapies could result in different Helicobacter pylori eradication rates.

Capillary electrophoretic separation of biologically active amines and acids using nanoparticle-coated capillaries

This manuscript describes dynamic coating of capillaries with poly(L‐lysine) (PLL) and silica nanoparticles (SiO2 NPs) and use of the as‐prepared capillaries for the separation of biogenic amines and acids by CE in conjunction with LIF detection. The directions of EOF are controlled by varying the outmost layer of the capillaries with PLL and SiO2 NPs, respectively. Over the pH range 3.0–5.0, the (PLL–SiO2NP)n–PLL capillaries have an EOF toward the anodic end and are more suitable for the separation of acids with respect to speed, while the (PLL–SiO2NP)n capillaries have an EOF toward the cathodic end and are more suitable for the separation of biogenic amines regarding speed and sensitivity. The separations of standard solutions containing five amines and two acids by CE with LIF detection using (PLL–SiO2NP)2–PLL and (PLL–SiO2NP)3 capillaries were accomplished within 10 and 7 min, providing plate numbers of 3.8 and 5.0×104 plates/m for 5‐hydroxytryptamine (5‐HT), respectively. The LODs for 5‐HT and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) are 32 and 2 nM and 0.2 and 1.5 nM when using the (PLL–SiO2NP)2–PLL and (PLL–SiO2NP)3 capillaries, respectively. Identification and quantification of 5‐HIAA, homovanillic acid, and DL‐vanillomandelic acid in urine samples from a male before and after drinking green tea were tested to validate practicality of the present approach. The results show that the (PLL–SiO2NP)2–PLL capillary provides greater resolving power, while the (PLL–SiO2NP)3 capillary provides better sensitivity, higher efficiency, and longer durability for the separation of the amines and acids.

Systematic review with meta‐analysis: the efficacy of levofloxacin triple therapy as the first‐ or second‐line treatments of Helicobacter pylori infection

Levofloxacin triple therapy has been used for the first‐line and second‐line treatment of Helicobacter pylori infection for more than 10 years.

Spontaneous Clearance of Helicobacter pylori Colonization in Patients with Partial Gastrectomy: Correlates with Operative Procedures and Duration After Operation

BACKGROUND/PURPOSE For patients undergoing gastric surgery because of complications of peptic ulcers, such as bleeding or perforation in the pre-Helicobacter pylori eradication era, their infection status was not surveyed or it was neglected altogether. Previous reports have shown spontaneous clearance of H. pylori in these patients but the determining factors remain ill-defined. METHODS Seventy-six patients with previous partial gastrectomy for complicated peptic ulcers were enrolled prospectively. Patients with peptic ulcers but without gastrectomy were selected as a control group. Gastric biopsy specimens were obtained from each patient for histological H. pylori staining and rapid urease test on endoscopic evaluation. Spontaneous clearance of H. pylori colonization was defined when patients who were positive for H. pylori prior to operation became negative, without eradication treatment. RESULTS The prevalence of H. pylori colonization was significantly lower in patients with partial gastrectomy (22.4%, 17/76 vs. 67.1%, 51/76, p < 0.001). There was a trend towards decreasing prevalence of H. pylori colonization as time after operation increased: 1-15 years, 29.5% (13/44); 16-30 years, 13.6% (3/22); and > 31 years, 10% (1/10). The spontaneous clearance rate of H. pylori after partial gastrectomy was 43% (13/30). The time after operation in the spontaneous clearance group was longer than that in those without (20.8 +/- 11.7 vs. 12.1 +/- 11.0 years, p = 0.048). Billroth-II procedure had a higher bile reflux rate and a lower H. pylori infection prevalence than the Billroth-I procedure. CONCLUSION Spontaneous clearance of H. pylori develops in a certain number of patients who undergo distal gastrectomy. The clearance rate is related to operative procedures and time after operation.

Levofloxacin Sequential Therapy vs Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori: A Randomized Trial.

Objectives:The efficacy of levofloxacin triple therapy has fallen below 80% in the second-line treatment of Helicobacter pylori (H. pylori). We aimed to assess whether the levofloxacin sequential therapy is more effective than levofloxacin triple therapy in the second-line treatment.Methods:This open-label, randomized, multicenter trial was conducted between 2012 and 2015. H. pylori-infected subjects who failed from clarithromycin-based regimens (N=600) were randomized (1:1) to receive levofloxacin sequential therapy (LS: lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, levofloxacin, and metronidazole for another 5 days) or levofloxacin triple therapy (LT: lansoprazole, amoxicillin, and levofloxacin for 10 days). Successful eradication was defined as negative 13C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test.Results:The prevalence of clarithromycin, levofloxacin, and metronidazole resistance was 60, 17.6, and 36.9%, respectively. The eradication rates of LS and LT were 84.3% (253/300) and 75.3% (226/300), respectively, in the ITT analysis (P=0.006) and 86.3% (253/293) and 78.8% (223/283), respectively, in the PP analysis (P=0.021). The efficacies of both LS and LT were affected by levofloxacin resistance. The secondary resistance of levofloxacin was 66.7 and 73.9% after LS and LT, respectively. The efficacies of LS and LT were not affected by the CYP2C19 polymorphism.Conclusions:Levofloxacin sequential therapy was more effective than levofloxacin triple therapy, and it is recommended in the second-line treatment for H. pylori (Trial registration number: NCT01537055).