Once endoscopy and culture have been performed, SGT is superior to empirical 7 or 10 day triple therapy for first-line treatment. Further studies are needed to evaluate the effectiveness of SGT in clinical practice, especially when compared with currently recommended first-line quadruple therapies.

Background Susceptibility‐guided treatment has been proposed as a way to improve Helicobacter pylori eradication rates. Evidence on its efficacy for rescue therapy is very scarce. The aim of this study was to indirectly assess the applicability and effectiveness of susceptibility‐guided treatment by evaluating (a) the rate of acceptance of endoscopy, (b) its success in detecting resistances, and (c) infection cure rates in patients harboring strains found to be susceptible to the antibiotics administered in clinical trials in which the efficacy of second‐line treatments was reported. Methods A systematic review of studies evaluating second‐line H pylori treatment was carried out in multiple databases. Studies reporting antibiotic susceptibility evaluation and/or cure rates in patients harboring sensitive and resistant strains were selected. Data were extracted in duplicate. Results The systematic review identified 36 eligible studies. Acceptance was evaluated in only one study of 60 patients, of whom only 38 agreed to endoscopy. Among the 2890 patients who received endoscopy and culture, resistances were finally determined in 86.5%. Cure rate was 72.5% in the 113 patients harboring a clarithromycin‐susceptible strain after previous clarithromycin treatment, 93.5% in the 765 patients harboring a metronidazole‐susceptible strain, and 83.8% in the 192 patients harboring a levofloxacin‐susceptible strain. No studies with repeated administration of levofloxacin or metronidazole were found. Conclusion Even if the culture shows a clarithromycin‐sensitive strain, repeating clarithromycin after a first failure should be discouraged. Susceptibility‐guided treatment alone did not achieve adequate cure rates for rescue therapies. Additional measures are needed to design rescue treatments that consistently achieve excellent cure rates.

PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate.

Second-line Helicobacter pylori treatments achieving>90% cure rates are extremely heterogeneous. Quadruple therapy and 14-day treatments seem better than triple therapies and 7-day ones. No single characteristic of the treatments was related to excellent cure rates. Future approaches suitable for infectious diseases-thus considering antibiotic resistances-are needed to design rescue treatments that consistently achieve excellent cure rates.