Randomised Controlled Trial

Susceptibility-guided Therapy Versus Empiric Bismuth Quadruple Therapy for First-line Helicobacter Pylori Treatment

Qi Chen; Xiaohua Long; Yingjie Ji; Xiao Liang; Dongping Li; Hong Gao; Beili Xu; Ming Liu; Ying Chen; Yunwei Sun; Yan Zhao; Gang Xu; Yanyan Song; Lou Yu; Wei Zhang; Wenzhong Liu; David Y. Graham; Hong Lu

Disclosures

Aliment Pharmacol Ther. 2019;49(11):1385-1394. 

In This Article

Abstract and Introduction

Abstract

Background: Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness.

Aim: To test the effectiveness of susceptibility-guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first-line H pylori treatment in a region with high antimicrobial resistance.

Methods: We compared 14-day susceptibility-guided with empiric therapy using a multicentre superiority-design trial, which randomised H pylori infected subjects 3:1 to (a) susceptibility-guided therapies contained esomeprazole 20 mg and amoxicillin 1 g b.d. plus clarithromycin 500 mg, metronidazole 400 mg b.d., or levofloxacin 500 mg daily for susceptible infections or bismuth 220 mg b.d. and metronidazole 400 mg q.d.s. for triple-resistant infections; (b) Empiric therapy contained esomeprazole 20 mg, bismuth 220 mg b.d., amoxicillin 1 g and metronidazole 400 mg t.d.s. Primary outcome was H pylorieradication.

Results: Between February 2017 and March 2018, 491 subjects were screened and 382 were randomised. Both the susceptibility-guided and the empiric regimens were highly successful with per-protocol eradication rates of 97.7% (250/256) vs 97.6% (81/83, P = 1.00) and intent-to-treat eradication rates of 91.6% (262/286) vs 85.4% (82/96, P = 0.12). Overall, susceptibility-guided therapy was not superior to empiric therapy with 0.1% per-protocol (95% CI −3.1% to 3.2%) and 6.2% intent-to-treat (−0.3% to 12.7%) eradication difference. Both approaches had high adherence and low adverse event rates.

Conclusions: Both susceptibility-guided and empiric therapies provided excellent eradication rates. Clinically, the choice would hinge on availability of susceptibility testing and/or a locally highly effective empiric therapy.

Introduction

Widespread use of antibiotics has resulted in increasing antimicrobial resistance and a fall in cure rates for many infectious diseases.[1] China has a high prevalence of antibiotic resistance and the currently recommended first line Helicobacter pylori (H pylori) therapy is bismuth quadruple therapy.[2,3] However, tetracycline has become difficult to obtain in many areas including in China.[3] Randomised controlled trials have shown that a modified bismuth quadruple therapy that substituted amoxicillin (1 g t.d.s) for tetracycline (500 mg q.d.s.) remained highly effective.[4]

Classically, therapy for infectious diseases is based on local, regional or patient-specific antimicrobial susceptibility.[5] The need for H pylori culture and antimicrobial susceptibility testing became an increasing concern[6] and this is especially true in East Asia (China, Japan and Korea) where the prevalence of antimicrobial resistance is high[7] and an endoscopy-and-treat strategy has been widely developed.[2,3] Many previous susceptibility-guided therapies had significant limitations such as including susceptibility testing for only one or two antibiotics (clarithromycin or/and metronidazole), used relatively ineffective regimens (eg, short treatment durations), employed regimens ineffective for multiresistant infections despite a high prevalence of multidrug-resistant infections, or used suboptimal empiric comparators.[8–16]

Here, we designed a strategy to link the most appropriate susceptibility-guided regimen for each patient based on susceptibility patterns, tolerability and safety. All treatment regimens were 14 days and used "double dose PPI".[17] The susceptibility-based regimens consisted of clarithromycin, metronidazole or levofloxacin triple therapies for susceptible infections or a modified bismuth quadruple therapy for multidrug-resistant infections. The comparator empiric therapy was locally proven highly effective empiric bismuth quadruple therapy containing amoxicillin and metronidazole.[4,18,19]

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