Treatment of Helicobacter pylori infection: Current and future insights

Table 1 Numbers of different regimens for Helicobacter pylori infection treatments

Regimens	Patients (n)	Eradication rate	Conclusion	Ref.
High dose dual therapies
Amoxicillin 750 mg and esomeprazole 40 mg every 8 h for 14 d	36	The ITT cure was achieved in 72.2% (95%CI: 56%-84%) and PP cure achieved in 74.2% (95%CI: 56%-87%)	However, the regimen was not sufficient to eradicate 90% H. pylori but, the result was positive in that dual therapy with the doses tested here was at least as successful as empiric triple therapy with a PPI, amoxicillin, and clarithromycin	[42]
Amoxicillin 1 g t.d.s. and rabeprazole 20 mg t.d.s. for 2 wk	149	Eradication success PP and ITT was 75.4% (95%CI: 68.3%-82.4%) and 71.8% (95%CI: 64.6%-79.0%), respectively.	Eradication success of 75% on PP analysis as a first rescue therapy including 2-wk high dose PPI-amoxicillin dual therapy was achieved. Following these patients by a second rescue therapy with PPI triple therapy were highly successful in achieving eradication rate (> 90%) in H. pylori treatment failures	[43]
Amoxicillin 1 g b.i.d. and omeprazole 20 mg q.i.d. for 14 d	74	Eradication rate of 81.1% in the dual therapy group vs 63.8% in the triple therapy group was achieved	Dual therapy is more effective, cost-effective and is less risky in terms of side effects compared to standard triple therapy in patients with dyspepsia	[44]
Amoxicillin 1 g and dexlansoprazole 120 mg each twice a day at approximately 12-h intervals for 14 d	13	PP and ITT treatment success were both 53.8% (95%CI: 25%-80%)	However compliance was 100% and reported side effects were mild and none interrupted therapy but dexlansoprazole, despite being administered at high dose, failed to achieve an intragastric milieu in treatment-natıve patients	[41]
Amoxicillin 750 mg and rabeprazole 20 mg, 4 times/d for 14 d	150	In the ITT analysis, H. pylori was eradicated in 95.3% of treatment-naïve patients (95%CI: 91.9-98.8%) and in 89.3% of treatment-experienced patients (95%CI: 80.9%-97.6%)	High-dose dual therapy is superior to standard regimens as empirical first-line or rescue therapy for H. pylori infection with similar safety profiles and tolerability	[45]
Triple therapies
Amoxicillin 1 g and metronidazole 500 mg both three times a day plus esomeprazole 40 mg twice a day	136	Eradicationrates were 82.4% (95%CI: 74.7%-88.1%) by ITT analysis and 88.2% (95%CI: 81.2%-92.8) by PP analysis.	Cure rates of the combination of esomeprazole, amoxicillin and metronidazole are high and the treatment was well tolerated	[47]
Amoxicillin 1 g twice daily, levofloxacin, 500 mg, once daily and esomeprazole 20 mg twice daily for 7 d	345	ITT analysis eradication rates 78.1% (95%CI: 69.4%-85.3%), 78.3% (95%CI: 69.6%-85.4%), and 82.8% (95%CI: 74.6%-89.1%) for tripletherapy, standard sequential therapyand levofloxacin-containing sequential therapyre spectively and PP analysis eradication rates were 80.9% (95%CI: 72.3%-87.8%), 82.6% (95%CI: 74.1%-89.2%), and 86.5% (95%CI: 78.7%-92.2%), respectively, for the three therapies	Standard sequential therapy and 7-d levofloxacin triple therapy produced unacceptably therapeutic efficacy in China. Only levofloxacin-containing sequential therapy achieved borderline acceptable result	[48]
Amoxicillin 50 mg/kg per day, q.d.s., nifuratel 30 mg/kg per day, q.d.s. and bismuthsubcitrate 8 mg/kg per day, q.d.s. for 10 d	73	PP and ITT treatment success were both 86% (95%CI: 76.6%-93.2%)	The combination of nifuratel, bismuth subcitrate, and amoxicillin was a tolerable and effective regimen for H. pylori eradication	[49]
Amoxicillin 1 g, clarithromycin 500 mg and rabeprazole 20 mg all twice daily for 10 d in comparison with half dose	115	Eradication rates were 77.6% (95%CI: 66.9%-88.3%) in the standard dose vs half dose 77.2% (95%CI: 66.3%-88.1%) on ITT analysis. PP eradication rates were 78.9% (95%CI: 68.4%-85.9%) and 81.5% (95%CI: 71.1%-91.8%) respectively	A half-dose 10-d regimen is equally effective but cheaper and better tolerated than its standard-dose regimen	[50]
Amoxicillin 1 g, clarithromycin 500 mg plus either omeprazole 20 mg or esomeprazole 40 mg twice daily for 1 wk	200	For patients classified as homologous extensive metabolizers, the PP H. pylori eradication rate was significantly higher in the esomeprazole group than in the omeprazole group (93% vs 76%, P < 0.05)	Only for extensive metabolizers esomeprazole 40 mg twice daily for triple therapy improve the H. pylori eradication compared to omeprazole-based therapy	[51]
Amoxicillin 1 g, clarithromycin 500 mg and lansoprazole 30 mg, all taken twice a day for 14 d	1463	Comparing effectiveness of standard 14-d regimen of triple therapy with that of the four-drug regimens given concomitantly or sequentially therapy showed the eradication rate with standard therapy was 82.2%, and concomitant therapy (73.6%) and finally by sequential therapy (76.5%)	Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites of Latin America	[52]
Quadruple therapies
Tetracycline 500 mg q.d.s., levofloxacin 500 mg o.d. esomeprazole 40 mg b.d and tripotassium dicitratobismuthate 120 mg q.d.s.	24	The eradication rates according to ITT and PP analysis were both 95.8% (95%CI: 87.8%-103.8%)	The 10-d quadruple therapy achieves a very high eradication rate for H. pylori infection after failure of sequential therapy	[56]
Amoxicillin 1 g b.d., esomeprazole 40 mg b.d., levofloxacin 500 mg o.d. and bismuth 240 mg b.d. for 14 d	200	PP and ITT eradication rates were 91.1% (95%CI: 87%-95%) and 90% (95%CI: 86%-94%)	14-d bismuth - and levofloxacin-containing quadruple therapy is effective second-line therapy in patients whose sequential or concomitant therapies have failed	[10]
lansoprazole (30 mg twice daily) and bismuth potassium citrate (220 mg twice daily), along with 500 mg tetracycline and 400 mg metronidazole 4 times daily (LBTM), 500 mg tetracycline and 100 mg furazolidone 3 times daily (LBTF), 1000 mg amoxicillin 3 times and 500 mg tetracycline 4 times daily (LBAT), or 1000 mg amoxicillin and 100 mg furazolidone 3 times daily (LBAF)	424	PP rates of eradication were greater than 90%for all regimens: 93.1% for LBTM (95%CI: 88.1%-98.0%), 96.1% for LBTF (95%CI: 92.4%-99.8%), 94.6% for LBAT (95%CI: 90.0%-99.2%), and 99.0% for LBAF (95%CI: 97.0%-100%). The ITT response rates were 87.9% for LBTM (95%CI: 81.7%-94.0%), 91.7% for LBTF (95%CI: 87.1%-96.3%), 83.8% for LBAT (95%CI: 76.8%-90.9%), and 95.2% for LBAF (95%CI: 91.1%-99.3%)	Four bismuth-containing quadruple therapies achieved greater than 90% eradication of H. pylori in patients who did not respond to previous treatment, including patients with metronidazole resistance	[57]
Amoxycillin 1000 mg, ranitidine 300 mg and bismuth subcitrate 240 mg b.d., with either furazolidone 200 mg b.d. (RABF), or metronidazole 500 mg b.d. (RABM) for 2 wk	106	ITT eradication rates were 75% and 55% (P = 0.03) and per protocol eradication rates were 82% and 56% (P = 0.006) in the RABF and RABM groups, respectively	Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H. pylori eradication rate in Iranian duodenal ulcer patients	[60]
Tetracycline hydrochloride 375 mg, metronidazole 375 mg and bismuth subcitrate potassium 420 mg q.d.s., and omeprazole 20 mg b.d. for 10 d	64	Eradication rates ranged from 93.2% to 93.8% in the ITT population, and from 94.7% to 95.0% in the PP population	A quadruple regimen of bismuth, metronidazole and tetracycline plus omeprazole produces a high eradication rate in subjects previously failing H. pylori eradication regimens	[61]
Tetracycline 500 mg q.d.s., esomeprazole 40 mg b.d. and bismuth subcitrate 300 mg q.d.s. plus either levofloxacin 500 mg once daily or metronidazole 500 mg q.d.s. for 10 d	150	ITT analysis revealed that both groups showed similar eradication rates. levofloxacin group, 78.9% (95%CI: 69.7%-88.1%) and metronidazole group, 79.7% (95%CI: 70.5%-88.7%)	The 10-d bismuth quadruple therapies with high-dose metronidazole or levofloxacin were effective even in areas with high resistance. These two therapies were equally safe and tolerated	[62]
Amoxicillin 1 gram, clarithromycin 500 mg, metronidazole 500 mg esomeprazole 40 mg given twice a day for 10 d	232	ITT analysis demonstrated similar eradication rates for sequential 92.3%; (95%CI: 87.5%-97.1%) and concomitant therapy 93.0% (95%CI: 88.3%-97.7%). PP eradication results were similar for sequential 93.1%; (95%CI: 90.7%-95.5%) and concomitant therapy 93.0% (95%CI: 88.3%-97.7%)	Sequential or concomitant therapy with a PPI, amoxicillin, clarithromycin, and an imidazole agent are equally effective and safe for eradication of H. pylori infection. Concomitant therapy may be more suitable for patients with dual resistance to antibiotics.	[67]
Amoxicillin 1 g and omeprazole 40 mg twice daily for 14 d, clarithromycin 500 mg and nitroimidazole 500 mg twice daily (for the final 7 d)	343	In PP analysis, rates of eradication for hybrid and concomitant therapies were 92% and 96.1%, respectively. In ITT analysis, rates were 90% and 91.7% respectively	Optimized non bismuth quadruple hybrid and concomitant therapies cured more than 90% of patients with H. pylori infections in areas of high clarithromycin and metronidazole resistance	[68]
Concomitant therapy: Same 4 drugs taken concurrently, twice daily for 14 d
Sequential therapy
Amoxycillin 1 g b.d. plus omeprazole 20 mg b.d. for the first 5 d, followed by clarithromycin 500 mg b.d. tinidazole 500 mg b.d. and omeprazole 20 mg b.d., for the remaining 5 d	52	The eradication rate was 98% (95%CI: 94.3%-100%) with ITT analysis	The 5 plus 5 d therapy as sequential therapy achieved sufficient eradication rate	[70]
Amoxicillin plus omeprazole for 5 d, followed by omeprazole plus clarithromycin plus tinidazole for another 5 d	78	H. pylori eradication was achieved in 36 children receiving sequential treatment 97.3% (95%CI: 86.2%-99.5%) and 28 children receiving triple therapy 75.7% (95%CI: 59.8%-86.7%)	10-d sequential treatment achieves a higher eradication rate than standard triple therapy	[71]
Amoxicillin 1000 mg b.i.d. and pantoprazole 40 mg b.i.d. for the first 5 d, followed by pantoprazole 40 mg b.i.d., clarithromycin 500 mg b.i.d. and metronidazole 500 mg b.i.d. in the remaining 5 d	175	Comparison of standard triple therapy with a sequential schema represented two treatment groups did not differ with regard to H. pylori eradication rate for both ITT population (63.9% vs 71.4% for standard and sequential therapy respectively, P = 0.278) and per protocol population (65.9% vs 74.1% for standard and sequential therapy respectively, P = 0.248)	In the present study, the two treatments resulted in similar rates of eradication, and both treatments were relatively ineffective	[72]
Amoxicillin 1 g and lansoprazole 30 mg for the first 7 d or 5 d, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 d or 5 d	900	The eradication rate was 90.7% (95%CI: 87.4%-94.0%) in the 14 d, 87.0% (95%CI: 83.2-90.8) in the 10 d group, and 82.3% (95%CI: 78.0-86.6) in the triple therapy 14-d group	This study support to the use of sequential treatment as the standard first-line treatment for H. pylori infection	[76]
Amoxicillin 1 g plus omeprazole 20 mg for the first 5 d, followed by 20 mg of omeprazole, 500 mg of clarithromycin, 500 mg of metronidazole, for the remaining 5 d	158	Comparing 10 d-sequential therapy with PPI-based triple therapy revealed eradication rate for 10 d-sequential therapy was 77.9% (60/77) by ITT and 85.7% (60/70) by PP analysis, but eradication rates in PPI-based triple therapy were 71.6% (58/81) and 76.6% (58/76) by ITT and PP analysis, respectively	The 10-d sequential therapy regimen failed to achieve significantly higher eradication rates than PPI-based triple therapy	[77]
Amoxicillin 1 g b.d. plus PPI b.d. for the first 5 d, followed by a PPI b.d. clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. for the next 5 d	139	The ITT eradication rate was 84.2% (95%CI: 77%-90%) and the PP cure rate 90.7% (95%CI: 84%-95%)	Sequential treatment seems highly effective for eradicating H. pylori	[75]
Amoxicillin 1 g plus omeprazole 20 mg followed by 5 d omeprazole 20 mg, clarithromycin 500 mg and tinidazole 500 mg or followed by 5 d omeprazole 20 mg, levofloxacin 250 mg and tinidazole 500 mg or followed by 5 d omeprazole 20 mg, levofloxacin 500 mg and tinidazole 500 mg twice daily	375	Eradication rates in the ITT analyses were 80.8% (95%CI: 72.8%-87.3%) with clarithromycin sequential therapy, 96.0% (95%CI: 90.9%-98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95%CI: 92.0%-99.1%) with levofloxacin-500 sequential therapy	Levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy	[79]

ITT: Intention-to-treat; CI: Confidence interval; PP: Per protocol; H. pylori: Helicobacter pylori; PPI: Proton-pump inhibitor; t.d.s.: Ter die sum endum; b.i.d.: Bis in die; q.i.d.: Quater in die; q.d.s.: Quater die sum endum; b.d.: Twice daily.