Practical Aspects in Choosing a Helicobacter pylori Therapy

Matrix erosion is unavoidable during the release of poorly soluble drugs from gastric floating delivery system (GFDDS), which shortens the floating time and diminishes drug release. We fabricated a core-shell system (CSS) consisting of a low-density drug-loaded shell and a floating core using multi-nozzle semi-solid extrusion (SSE) 3D printing technology. The clarithromycin (CAM) loading capacity of the shell was 81.7%. The floating core paste provided structural support during printing and formed a hollow structure in CAM CSS, which increased the buoyancy in the early stage of drug release. In addition, the floating core had numerous micro-airbags that swelled when the solution penetrated the core, and generated CO₂. The micro-airbag structure and CO₂ generation further increased the buoyancy of CSS. The CAM CSS achieved 74.5% (w/w) drug loading, 8 h sustained release, and immediate and prolonged floating (>10 h). This structure of CSS and floating core provide a novel perspective for constructing a stable gastric floating drug delivery system.

Antibiotic resistance of Helicobacter pylori (H. pylori) treatment is on the rise, and is affecting the efficacy of current used therapeutic regimens.

We aimed to enhance the understanding of antimicrobial resistance rates of H. pylori strains recovered from patients at Theodor Bilharz Research Institute Hospital in Egypt, as a mandatory step before starting treatment.

Mutant genes conferring metronidazole, amoxicillin, clarithromycin, and tetracycline resistance were detected in 60 H. pylori strains recovered from patients who underwent upper endoscopic examination. Patients were considered to be infected with H. pylori when rapid urease test and detection of 16S rRNA in gastric biopsies recorded positive. Molecular detection of resistant genes to metronidazole (rdx gene) and amoxicillin (pbp1A gene) was carried out by conventional PCR followed by sequencing of PCR products. While detection of 23S rRNA gene conferring clarithromycin resistance and detection of 16S rRNA mutation gene conferring tetracycline resistance were carried out by real-time PCR.

H. pylori resistance rates to metronidazole, and amoxicillin were 25% and 18.3% respectively. While for clarithromycin and tetracycline, point mutations in 23S rRNA types A2142G and A2143G and in 16S rRNA of H. pylori were assessed by real time PCR assay respectively. Resistance mutant genes were found to be 6.7% of clarithromycin and 1.7% of tetracycline. Combined resistance rates to metronidazole and amoxicillin was (11.6%) followed by metronidazole and clarithromycin (5%), while patterns of clarithromycin and amoxicillin (1.6%), metronidazole, clarithromycin and amoxicillin (1.6%) were revealed.

Data concerning antimicrobial resistance genes play an important role in empiric treatment of H. pylori infection. According to our results, H. pylori resistance to metronidazole and amoxicillin was relatively high. Clarithromycin is still a good option for first line anti-H. pylori treatment. Combined resistant strains are emerging and may have an effect on the combination therapy.

La infección por Helicobacter pylori afecta aproximadamente al 50% de la población española y es causante de la gastritis crónica, la úlcera péptica y el cáncer gástrico. Se han llevado a cabo hasta el momento, en nuestro país, 3 reuniones de Consenso sobre el manejo de la infección por H. pylori (la última de ellas en 2012). Los cambios en los esquemas de tratamiento y la creciente evidencia disponible al respecto han justificado la organización de esta IV Conferencia Española de Consenso en marzo de 2016, centrada en el tratamiento de esta infección. Participaron 19 expertos sobre el tema, que realizaron una búsqueda sistemática de la evidencia científica y elaboraron una serie de recomendaciones que fueron sometidas a un proceso de interacción de votaciones anónimas seriadas mediante metodología Delphi. Para clasificar la evidencia científica y la fuerza de las recomendaciones se utilizó el sistema GRADE. Este consenso establece, como punto de partida, un aumento de la exigencia en la eficacia de los tratamientos recomendados, que deben alcanzar, o preferiblemente superar, el 90% de curación al ser administrados de forma empírica. De este modo, tanto en primera como en segunda línea se recomiendan tratamientos cuádruples con o sin bismuto, generalmente prescritos durante 14 días. El tratamiento cuádruple sin bismuto concomitante, que incluye un inhibidor de la bomba de protones, claritromicina, amoxicilina y metronidazol, se recomienda como primera línea. En el presente consenso se revisan también con detalle otras alternativas de tratamiento tanto de primera línea como de rescate.

Helicobacter pylori approximately infect 50% of Spanish population and causes chronic gastritis, peptic ulcer and gastric cancer. Until now, three consensus meetings on H. pylori infection had been performed in Spain (the last in 2012). The changes in the treatment schemes, and the increasing available evidence, have justified organizing the IV Spanish Consensus Conference (March 2016), focused on the treatment of this infection. Nineteen experts participated, who performed a systematic review of the scientific evidence and developed a series of recommendation that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. As starting point, this consensus increased the minimum acceptable efficacy of recommended treatments that should reach, or preferably surpass, the 90% cure rate when prescribed empirically. Therefore, only quadruple therapies (with or without bismuth), and generally lasting 14 days, are recommended both for first and second line treatments. Non-bismuth quadruple concomitant regimen, including a proton pump inhibitor, clarithromycin, amoxicillin and metronidazole, is recommended as first line. In the present consensus, other first line alternatives and rescue treatments are also reviewed and recommended.

The resistance of Helicobacter pylori to antibiotics has increased the need for new empirical, first-line treatments. However, the efficacy of sequential therapy (ST) and concomitant therapy (CT) compared with triple therapy (TT) has not been adequately evaluated.

In this study, we evaluated the efficacy of these empirical three regimens.

The 517 patients enrolled in the study were prospectively randomized to receive 10 days of TT (n = 171), ST (n = 170), and CT (n = 176) at 5 university-affiliated hospitals from May 2013 to March 2015. The post-treatment H. pylori status was determined using the ¹³C-urea breath test.

The baseline characteristics were similar among the three groups. The intention-to-treat eradication rates were 62.6%, 70.6%, and 77.8% in the TT, ST, and CT groups, respectively (p < 0.01). The corresponding per-protocol eradication rates were 82.8%, 89.5%, and 94.4%, respectively (p < 0.01). There were no significant differences in the compliance, side effects, and follow-up loss rates.

A higher eradication rate was achieved with empirical 10-day ST, and CT than with the TT regimen, with similar rates of compliance and treatment side effects.