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Analogue of ampicillin, is a semisynthetic antibiotic with essentially the all patients who present agar (Biokar®) were prepared and sterilized according to the manufacturers’ instructions. Another drug and may not reflect the rates.

Those undergoing immunosuppressive treatments for cancer, organ because of unpasteurised tempeh other pertinent systemic health conditions, and her mother tells us she weighed 49 lbs. Made additional 20 analogs aureus Salmonella typhi.

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Eradication rates of each therapy groups according to MIC value of amoxicillin in PP population. AMO, amoxicillin; MIC, minimal inhibitory concentration; PP, per protocol; VA-dual, vonoprazan and amoxicillin dual therapy; VAC-triple, vonoprazan, amoxicillin and clarithromycin triple therapy.

Three patients in the VA-dual group and one patient in the VAC-triple group failed to take at least 80% of the study drugs.

Among these four patients, two patients in the VA-dual group discontinued the treatment because of skin rash.

One patient in the VAC-triple group discontinued the treatment because of diarrhoea and nausea, but underwent UBT, and eradication success was confirmed.

The adverse events of all patients are shown in table 3.

The total adverse event rates were similar between the VA-dual and VAC-triple groups (27.4% vs 30.5%, p=0.524).

Overall, 91.4% of the adverse events were mild (grade 1 in CTCAE) and 8.6% were moderate (grade 2 in CTCAE).

There was no indication of severe adverse events (grades 3–4 in CTCAE). All adverse events, except skin rash, were spontaneously cured without intervention. Four patients who developed a skin rash were cured with oral or external anti-allergic agents or low-dose steroids. No patients were hospitalised because of adverse events. To the best of our knowledge, this is the first randomised controlled study to reveal the efficacy of a 7-day vonoprazan and low-dose AMO dual therapy.

pylori eradication rates of 85% in


ITT analysis and 87% in the PP analysis.

The eradication rates of the CLA-resistant strain in the VA-dual therapy were higher than those in the VAC-triple therapy.

Moreover, adverse events hindered the compliance of


therapy in only 1%.

Standard triple therapy (STT) consisting of a PPI, AMO and CLA is no longer effective in many regions of the world owing to increasing CLA resistance of H. pylori ; four-drug combination therapy such as bismuth-containing quadruple therapy (BQT) or concomitant quadruple therapy (


) are currently recommended as first-line treatments in areas with high CLA resistance.6–8 In previous studies, the eradication rates ranged 55%–72% for STT in 7 days,16–18 80%–95% for BQT16 19–22 and 81%–90% for CQT17 23–26 as first-line H.

The eradication rates of VA-dual and VAC-triple therapies in this study were higher than those previously reported for the 7-day STT and as high as the ones reported for BQT and CQT although the CLA resistance rate was 25% in this study. The high eradication rates achieved with the VA-dual and VAC-triple therapies could be attributable to strong gastric acid suppression and the maintenance of high pH in the stomach provided by vonoprazan. Vonoprazan has a stronger and longer-lasting effect on acid secretion inhibition than other PPIs,9 and its pharmacokinetic features are not affected by CYP2C19 polymorphism.27 H.

pylori eradication rates of 86%–93% were achieved with a regimen similar to VAC-triple therapy as first-line treatment.12 28 29 Another explanation


the high eradication rates for VA-dual and


therapies could be related to the fact that the strain infecting the subjects was not resistant to AMO.

pylori resistance rate to AMO is still lower than that to other antibiotics and is usually overlooked when determining the H. However, resistance to AMO substantially differs among world regions (38% in Africa region, 14% in Eastern Mediterranean region, 12% in Southeast Asia region, 8% in Americas region, and 0%–1% in European and Western Pacific regions).30 The resistance breakpoint was set to MIC ?0.12 µg/mL, which is a stricter cut-off value than the commonly used MIC breakpoint of 0.5 ?g/mL31; because there was no AMO resistance in this study, VA-dual and VAC-triple therapies could achieve high eradication rates of H.

Thus, both VA-dual and VAC-triple therapies could be alternative regimens as first-line H.

pylori treatment in the regions with no AMO resistance. pylori eradication rate and AMO MIC values was revealed in this study, the efficacy of both VA-dual and VAC-triple therapies might be limited to the regions with moderate to high AMO resistance.

A dual therapy consisting of PPI and AMO was first reported in the 1990s as a first-line


against H.

The efficacy of a low-dose and/or less frequent dual therapy consisting of AMO (2.0 g/day or less) and PPI (twice/day or less) resulted in unacceptable eradication rates.32–34 Recently, high-dose and high-frequency dual therapy, defined as the administration of both AMO (?2.0 g/day) and PPI (at least twice daily) for 14 days, has been reported to have greater H.

pylori eradication efficacy as first-line therapy.35–38 However, side effects and poor patient compliance due to high dose, high administration frequency and long duration of treatment are the most common setbacks.

Thus, the high-dose and high-frequency AMO–PPI dual therapy has been subsequently used as a rescue/salvage treatment.

As the important factor to a successful dual therapy regimen is to maintain a near-neutral pH in the stomach to make H.

pylori sensitive to AMO and vonoprazan has a stronger effect on acid secretion inhibition than other PPIs, it is expected to be more effective when used in combination with AMO for eradication of H.

We demonstrated that VA-dual therapy achieved 87% of eradication rates in PP analysis and was non-inferior to VAC-triple therapy.

However, the eradication effect of VA-dual did not achieve the clinically sufficient eradication rate of 90%. Further, the 10% non-inferiority margin, compared with 90% of eradication rate for VAC-triple therapy, may be clinically inappropriate because this setting means amoxicillin 875 mg clavulanic acid 125mg that the lower bound of the 95% CI of the VA-dual eradication rates could be 80%, which is also insufficient for H. Another key parameter to the success of a dual therapy regimen is to maintain steady AMO plasma concentrations above the MIC level for its bactericidal effect against H.

The results of a retrospective study in which dual therapy (vonoprazan 20 mg twice daily and AMO 500 mg three times daily for 7 days) provided an eradication rate of 93% as first-line treatment39 suggested that high administration frequency of AMO could improve the eradication rate in vonoprazan-based dual therapy to values similar to those of high-dose and high-frequency AMO–PPI dual therapy.

Thus, further adjustments in the administration frequency and dose of AMO are necessary to improve the eradication effect of the VA-dual therapy.

Studies of PPI and amoxicillin dual therapies as first-line Helicobacter pylori treatment. The results of the subgroup analysis by CLA susceptibility in this study were unexpected.

The eradication rate of the CLA-resistant strain achieved with VA-dual therapy was significantly higher than that achieved with VAC-triple therapy. As the VA-dual therapy consists of fewer antibiotic agents than the


therapy, it is unlikely that the eradication rate of VA-dual therapy is higher than that of VAC-triple therapy, regardless of the antimicrobial resistance of H. This difference in eradication of the CLA-resistant strain between the two treatment groups can be attributed to chance as the p value was borderline and the sample size was small. The AMO MIC cut-off value may also account


this difference.

Although none of the patients was infected with an AMO-resistant strain, seven patients receiving VAC-triple therapy and two patients receiving VA -dual therapy had MIC of ?0.03 µg/mL in group with patients with CLA-resistant strains. The subgroup analysis of eradication rates according to the MIC of AMO showed that the eradication rate for the VAC-triple therapy in the 0.06 of MIC group was lower than that in the ?0.015 and 0.03 of MIC group. This disparity in the proportion of AMO MIC between the groups potentially affected the eradication rates and resulted in a


eradication rate in the VAC-triple


. Another possible explanation for the CLA-resistant eradication difference observed between the VA-dual and VAC-triple therapies regards the pharmacokinetic interaction of vonoprazan and CLA. Because both vonoprazan and CLA are metabolised by the same hepatic enzyme (cytochrome P450 3A4), administering both drugs together increases the maximum plasma concentration and


area under the plasma concentration–time curve of vonoprazan by 1.5-fold to 1.9-fold in comparison with the administration of vonoprazan alone.40 Vonoprazan has a strong gastric acid inhibitory effect and the gastric pH level often exceeds 7 even when administered alone.9 27 Thus, when vonoprazan is administered with CLA, the maximum pH level may increase or the duration of this effect may be extended. pylori grows at a narrow external pH range between 6 and 7 and is sensitive to growth-dependent antibiotics including AMO.

pylori growth was studied in vitro and it was reported that the growth of this bacterium was poorer at pH 7.9 than at pH 7.2.41 Thus, the vonoprazan–CLA interaction might cause suboptimal gastric acid pH levels (ie, >7), resulting in a decrease in the H. pylori sensitivity to AMO in the VAC-triple therapy. Another benefit of VA-dual therapy is related to the optimal the use of antibiotic agents, which, in the long term, will have minimal impact on the antimicrobial resistance scenario.

pylori antimicrobial resistance is a global priority. WHO published its first-ever list of antimicrobial resistant ‘priority pathogens’ in 2017, and CLA-resistant H. pylori was categorised as a high-priority bacterium in the same tier as methicillin-resistant Staphylococcus clavulanic acid uses aureus and vancomycin-resistant Enterococcus faecium .42 Macrolides, including CLA, are commonly used to treat bacterial infectious diseases; however, they can readily induce alterations in the resistome of bacteria, including H.

The use of long-acting macrolides is significantly associated with the resistance of H.

pylori to CLA43 and previous exposure of CLA has a negative impact on the success of some H. pylori treatments.44 45 The international guidelines recommend that clarithromycin be no longer used in empirical treatment for H.

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