Author(s): Thung, I; Aramin, H; Vavinskaya, V; Gupta, S; Park, JY; Crowe, SE; Valasek, MA | Abstract: BackgroundHelicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.AimTo review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms.MethodsA PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.ResultsThe prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced.ConclusionsSince the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.

/pdf/review-article-the-global-emergence-of-helicobacter-pylori-1aig52cifc.pdf

Review article: the global emergence of Helicobacter pylori antibiotic resistance.

https://www.gastro.theclinics.com/article/S0889-8553(15)00049-7/pdf

How to Effectively Use Bismuth Quadruple Therapy: The Good, the Bad, and the Ugly.

Background Antimicrobial resistance is a major determinant of Helicobacter pylori treatment failures. We conducted a population-based survey to monitor changing antimicrobial susceptibility of H. pylori isolates in Taiwan, with a focus on combinatorial effects of synergism and the influence of acidity. Methods H. pylori isolates from endoscopic specimens taken from patients enrolled at two medical centers were obtained between January 2008 and December 2009. Minimum inhibitory concentrations (MICs) were determined by agar dilution and E test methods. Agar media of varying pH (pH 7.3, 6.0, or 5.0) were used to assess whether acidity influences the bactericidal effects of the agents tested. Time-kill assays were used to assess for synergism between different drug combinations. Results A total of 176 non-duplicate H. pylori isolates from endoscopic specimens were tested. The following MIC 90 (mg/L) (susceptible) results were obtained at neutral pH 7.3: amoxicillin, 0.25 (100%); tetracycline, 0.5 (100%); metronidazole, 32 (67.6%); clarithromycin, 0.25 (90.3%); ciprofloxacin, 1 (92.0%); gemifloxacin, 0.5 (94.9%); levofloxacin, 1 (93.2%); and moxifloxacin, 1 (91.5%). A decrease in pH from 6.0 to 5.0 significantly decreased the antimicrobial activity of levofloxacin and moxifloxacin against H. pylori . For clarithromycin-susceptible isolates, levofloxacin combined with clarithromycin provided both synergistic and bactericidal effects. For clarithromycin-resistant isolates with amoxicillin hypersusceptibility (MIC Conclusion Amoxicillin, tetracycline, clarithromycin, and fluoroquinolones, but not metronidazole, showed good in vitro anti- H . pylori activity (>90% susceptible). Synergism was only observed for clarithromycin-susceptible isolates. Acidity adversely influenced the antimicrobial activity of levofloxacin against H. pylori .

Comparative in vitro antimicrobial susceptibility and synergistic activity of antimicrobial combinations against Helicobacter pylori isolates in Taiwan

Increasing rates of antimicrobial resistance to clarithromycin and metronidazole present challenges in maintaining optimal eradication rates. Knowledge of local antibiotic resistance and consumption pattern is important in selecting a reliable regimen. In addition, adverse effect profiles of therapeutic regimens are important and must be addressed to enhance compliance rates. Various methods of enhancing the eradication rates of Helicobacter pylori (H. pylori) have been investigated, including changing combinations or durations of established drugs, adding adjuvant drugs, or development of new molecules or agents. Bismuth-containing quadruple, sequential, concomitant, and levofloxacin-based triple therapies are replacing the long-standing standard of the triple regimen. Despite the encouraging results of these regimens, individualized approaches like treatment after antibiotics resistance test or CYP2C19 genotyping would be the mainstream of future therapy. Because scientific, economic, and technical problems make these advance therapies unfit for widespread use, future development for H. pylori therapy should be directed to overcome individualized antibiotic resistance. Although various novel regimens and additive agents have indicated favorable outcomes, more studies or validations are needed to become a mainstream H. pylori therapy.

Attempts to enhance the eradication rate of Helicobacter pylori infection.

The optimal therapy for Helicobacter pylori (H. pylori) infection should combine a high cure rate and a short treatment duration with a favorable side-effect profile and should maintain a low cost. Several strategies have been proposed to increase the H. pylori eradication rate, including the extension of the treatment duration to 14 d, the use of a four-drug regimen (quadruple, sequential, and concomitant treatments), and the use of novel antibiotics, such as levofloxacin. However, triple therapy remains the most widely accepted first-line treatment regimen in Brazil and the United States and throughout Europe. Because this therapy is limited by resistance to clarithromycin, other therapeutic regimens have been investigated worldwide. This review describes the current literature involving studies directly comparing these different therapies and their efficacies.

Pharmacological therapy used in the elimination of Helicobacter pylori infection: a review.

Introduction This study aimed to compare the efficacy and safety of quadruple therapy containing doxycycline and routine quadruple therapy for Helicobacter (H.) pylori rescue eradication in patients who had failed the one-week triple therapy. Methods Patients who failed the first-line eradication therapy were allocated into two groups. Group A patients (n = 43) were administered esomeprazole 20 mg, bismuth potassium citrate 220 mg, amoxicillin 1 g and doxycycline 100 mg, all bid for ten days, while Group B patients (n = 42) were administered esomeprazole 20 mg bid, bismuth potassium citrate 220 mg bid, metronidazole 400 mg bid and tetracycline 750 mg q.6h, for ten days. The results of H. pylori eradication were assessed with 13C urea breath test four weeks after the therapy, and the side effects were recorded. Results A total of 85 patients (average age 46.9 years) were enrolled in the study. Successful eradication rate for H. pylori was 72.5% in Group A and 64.1% in Group B, with no significant difference between the two groups. 11.6% (5/43) of patients from group A and 31.0% (13/42) from group B reported at least one adverse event. The adverse events of all 18 patients disappeared after the therapy ceased. Conclusion Quadruple therapy containing doxycycline is as effective as routine quadruple therapy for H. pylori rescue eradication. The regimen is well tolerated by most patients and causes fewer adverse events than routine quadruple therapy. Hence, it may be recommended as a suitable alternative H. pylori rescue regimen in China.

Doxycycline-based quadruple regimen versus routine quadruple regimen for rescue eradication of Helicobacter pylori: an open-label control study in Chinese patients.

Design and synthesis of dual functional porphyrin-based COFs as highly selective adsorbent and photocatalyst

A design of experiments (DoE) approach was applied to the development and optimization of the manufacturing process to prepare linagliptin. DoE techniques such as a central composite face-centered design and a fractional factorial design were applied to obtain the critical process parameters and establish the optimal reaction conditions. With process-related impurities determined and successfully removed, a robust high-yielding and high-purity procedure was identified, which has been successfully demonstrated at a 100 g scale level to prepare the desired product in a 68% overall isolated yield and high-performance liquid chromatography (HPLC) purity of around 99.9%. 

Process Development and Optimization of Linagliptin Aided by the Design of Experiments (DoE)

Development and validation of a stability-indicating RP-HPLC method for the determination of fifteen impurities in rivaroxaban.

Development of a Robust and Scalable Process for the Large-Scale Preparation of Vilazodone

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