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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.

For pediatric patients weighing ? 40 kg who every 8 hours (Max: 1 g/dose) children weighing 20 kg or more should be dosed according to the adult recommendations in severe infections or those.

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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 uses of amoxicillin capsules 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 VAC-triple 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 for 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 lower eradication rate in the VAC-triple group.

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 the 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 amoxicillin 1mg 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 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.

The resistance rates to metronidazole and levofloxacin have increased >15% in many regions of the world in recent years adding to the observed increase in CLA resistance.30 Thus, given the alarming increase of the rates of resistance to

CLA

and to various families of antibiotics, treatment strategies have to be re-evaluated and the best approach relies on the appropriate use of antibiotics for the treatment of H.

Therefore, antimicrobial susceptibility testing is the best way to optimise and reduce antibiotics for H.

pylori eradication treatment as well as the treatment of other common infections. However, antimicrobial susceptibility testing is not performed routinely in the clinical practice because of the invasiveness of the endoscopy procedure, the limited availability of laboratory culture facilities and cost concerns. The VA-dual therapy offers an alternative regimen for H.

pylori eradication treatment in the era of increasing antimicrobial resistance.



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