Second and third line treatment options for Helicobacter pylori eradication

Table 1 Summary of consensus reports on Helicobacter pylori therapy

Region	Consensus title	Year	1st line treatment recommendations	Salvage therapy recommendations	Ref.
South America	3rd Brazilian consensus	2013	PPI + amoxicillin 1 g and clarithromycin 500 mg twice daily for 7 d(Replace amoxicillin with furazolidone 200 mg twice daily for penicillin allergy)	PPI + levofloxacin 500 mg once daily + amoxicillin 1 g twice daily for 10 dorPPI + levofloxacin 500 mg once daily + furazolidone 400 mg once daily for 7-10 dorbismuth-based quadruple therapy for 10-14 d	[7]
24 countries: United Kingdom United States Spain Italian Germany France Ireland etc.	Management of Helicobacter pylori infection-the maastricht IV/florence consensusreport	2012	If clarithromycin resistance rate < 20%:PPI + amoxicillin + clarithromycinorbismuth-based quadruple therapy(Replace amoxicillin with metronidazole for penicillin allergy)If clarithromycin resistance rate > 20%:Bismuth-based quadruple therapyorNon-bismuth quadruple therapy (sequential/concomitant therapy)	2nd line rescue:if clarithromycin resistance rate < 20%:bismuth-based quadruple therapyorPPI + levofloxacin + amoxicillinif clarithromycin resistance rate > 20%:PPI + levofloxacin + amoxicillin3rd line rescue:antibiotic susceptibility test first	[6]
Global	Helicobacter pylori in developing countriesWorld Gastroenterology Organization Global Guideline	2011	PPI + amoxicillin + clarithromycin(replace amoxicillin with metronidazole for penicillin allergy)orbismuth-based quadruple therapy	Bismuth-based quadruple therapyorPPI + levofloxacin + amoxicillin	[8]
Asia Pacific	Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection	2009	PPI + amoxicillin + clarithromycin for 7 dorbismuth-based quadruple therapy	PPI-amoxicillin-metronidazole_orbismuth-based quadruple therapyorlevofloxacin-based triple therapyorrifabutin-based triple therapy	[1]
Japan	Guidelines for the Management of Helicobacter pylori Infection in Japan: 2009 Revised Edition	2009	PPI + amoxicillin + clarithromycin for 7 d	2nd line rescue:PPI + amoxicillin + metronidazole for 5-10 d3rd line rescue:PPI + amoxicillin + levofloxacin	[9]
Latin America	Latin-American Consensus Conference on Helicobacter pylori infection	2000	Omeprazole 20 mg, or lansoprazole 30 mg, or pantoprazole 40 mg, or rabeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1000 mg twice a day for 7–14 d (preferably 10 d)	No specific recommendations	[10]

PPI: Proton pump inhibitor.

Table 2 Second and third line treatment options and study results

	Reported eradication rates in studies	Ref.	Comments
Second line treatment options and study results
After failure of clarithromycin-triple therapy
Repeat PPI, amoxicillin and clarithromycin	46% (overall)	[55]	Not recommended
PPI, amoxicillin, metronidazole	87% (overall)	[55]	Feasible in Japan with < 10% metronidazole resistance rateBetter with extended duration1
	96% (ITT)	[77]
	100% (PP)	[77]
Bismuth-containing quadruple therapy: PPI, bismuth, tetracycline, metronidazole	78% (overall)	[55]	Better with extended duration1
	69.8% (ITT)	[54]
	82.2% (PP)	[54]
	84.2% (ITT)	[62]
	92.3% (PP)	[62]
	79.7% (ITT)	[63]
	90.8% (PP)	[63]
Bismuth-containing quadruple therapy: PPI, bismuth, amoxicillin, metronidazole	72% (overall)	[55]
Bismuth-containing quadruple therapy: PPI, bismuth, tetracycline, amoxicillin	73% (overall)	[55]
	61.4% (overall)	[73]
Bismuth quadruple therapy: PPI, bismuth, tetracycline, levofloxacin	78.9% (ITT)	[63]
	87.0% (PP)	[63]
PPI, amoxicillin and levofloxacin	76% (overall)	[55]	Better with extended duration1
	76.5% (overall)	[61]
PPI, levofloxacin, metronidazole	67.9% (ITT)	[62]
	73.1% (PP)	[62]
Sequential therapy: PPI and amoxicillin for 5 d, followed by PPI, levofloxacin, nitroimidazole for 5 d	78-95% (overall)	[55]
Moxifloxacin, PPI, amoxicillin	74.9% (overall)	[72]	14-d regimen better than 7-d regimen
	87.2% (ITT, overall)	[73]
After failure of PPI-clarithromycin-nitroimidazole/metronidazole
Bismuth-containing quadruple therapy: PPI, bismuth, tetracycline, metronidazole	85% (overall)	[55]
After failure of non-bismuth quadruple therapy
PPI, amoxicillin, levofloxacin	81% (overall)	[55]
Third line treatment options and study results
Susceptibility based selection therapy	88.6% (ITT and PP)	[86]	Rescue therapy was rifabutin, amoxicillin and PPI for 12 d
	90% (ITT and PP)	[86]	Rescue therapy was levofloxacin, amoxicillin and PPI for 10 d
	80.7% (ITT)	[82]
	82.6% (PP)	[82]
10 d sequential therapy: PPI, amoxicillin for 5 d, then PPI, levofloxacin and tetracycline for 5 d	67.23% (ITT)	[92]
	68.38% (PP)	[92]
Rifabutin-containing therapies	66% (55%-77%) (overall)	[84]	Rifabutin 300 mg/d dose is more effective than 150 mg/d
Rifabutin, amoxicillin, PPI	63% (overall)	[84]
Rifaximin, levofloxacin and PPI	65%	[85]	Failed first line clarithromycin-triple therapy and second-line bismuth-containing quadruple therapy
Sitafloxacin, rabeprazole, amoxicillin	75% (ITT)	[96]	Failed first line clarithromycin-amoxicillin PPI and failed second line metronidazole-amoxicillin-PPI
	80% (PP)	[96]
	78.2% (ITT)	[97]
	83.6% (PP)	[97]

¹Extended duration = 10 to 14-d regimen. PPI: Proton pump inhibitor; ITT: Intention-to-treat; PP: Per protocol.