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Concomitant therapy led to a non-statistically significant advantage (5%) over sequential therapy, coming closer to 90% cure rates. Both therapies showed an acceptable safety profile. ClincialTrials.gov: NCT01273441.

Background: A third line treatment is needed in roughly 5% of patients infected with Helicobacter pylori. Few data have been reported on efficacy of treatment regimens in these patients. Methods: A prospective trial was designed to study the effectiveness of third line treatment of H. pylori infection in ulcer patients. Two‐week quadruple, culture‐guided, combinations were used in 31 consecutive patients. Susceptibility to metronidazole and clarithromycin were studied by E‐test, and thereafter a predetermined treatment regimen was used. Compliance was evaluated by pill count, and eradication defined by negative urea breath test at 6 weeks. Results: Two main quadruple regimens were used in 29 patients. In spite of good compliance, the combination of omeprazole, tetracycline, bismuth and clarithromycin (OTBC) showed an eradication rate (per protocol analysis) of 36% (five out of 14; CI: 12.8–64.9), and if amoxycillin was used (OTBA) the rate was 67% (eight out of 12; CI: 34.9–90.1). The difference was not significant. No clinical factor was found to be associated with failure to eradicate. Conclusions: Third line treatment often fails to eradicate H. pylori infection. New strategies need to be developed and tested for this common clinical situation.

Quadruple therapy obtains a high eradication rate even in patients with clarithromycin- and metronidazole-resistant strains. Further randomized and controlled studies are warranted and are urgently needed.

Levofloxacin-based rescue therapy constitutes an encouraging empirical third-line strategy after multiple previous H. pylori eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, and tetracycline.

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The effectiveness of 'triple first' and 'quadruple first' strategies is similar, although the latter seems slightly more cost-effective.