Although susceptibility-guided therapy is frequently recommended for Helicobacter pylori infection, the evidence available to date supporting this strategy is limited. The aim of the present article is to review the advantages and limitations of the susceptibility-guided and the empirical strategies to treat this infection. We performed a bibliographic search to identify studies investigating H. pylori susceptibility-guided therapy. Culture is not the only way to assess antibiotic resistance, as different polymerase chain reaction-based approaches have been developed as alternative methods. For detecting H. pylori antimicrobial resistance, a molecular approach based on a stool sample might enable more convenient, time-saving methods. Unfortunately, the antimicrobial susceptibility cannot be obtained in all cases. Furthermore, antibiotic susceptibility testing in clinical practice yields useful information only for a few antibiotics: clarithromycin, metronidazole, and quinolones. In addition, susceptibility towards clarithromycin and metronidazole in vitro does not necessarily lead to eradication in vivo. In the case of H. pylori therapy failure, we should not re-administer any of the antibiotics against which H. pylori has probably become resistant. Our updated meta-analysis showed that susceptibility-guided treatment is not better than empirical treatment of H. pylori infection in first-line therapy if the most updated quadruple regimens are empirically prescribed, and similar efficacy results were also demonstrated with the two strategies for second-line therapy. Cumulative H. pylori eradication rate with several successive rescue therapies empirically prescribed reaches almost 100%. Finally, the studies that have evaluated the cost-effectiveness of the susceptibility-guided treatment have achieved contradictory results. In summary, we can conclude that the evidence is too limited to support the generalized use of susceptibility-guided therapy for H. pylori treatment in routine clinical practice, either as first-line or as rescue treatment. Nevertheless, it would be recommended that susceptibility tests are performed routinely, even before prescribing first-line treatment, in specialized centers with an interest in H. pylori management.
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