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Abstract
Background/Aims
Moxifloxacin-based sequential therapy showed an excellent eradication rate as the first line treatment of Helicobacter pylori (H. pylori) infection. However, to the best of our knowledge, there were only a few studies on the treatment of those with failed moxifloxacin-based sequential therapy. Hence, this study was to investigate the efficacy of bismuth-containing quadruple therapy in those with failed moxifloxacin-based sequential or reverse sequential therapy for H. pylori eradication.
Methods
Between January 2013 and March 2016, we retrospectively analyzed patients who failed to eradicate H. pylori using moxi-floxacin-based sequential (rabeprazole 20 mg bid and amoxicillin 1 g bid for 5–7 days, followed by rabeprazole 20 mg bid, metronidazole 500 mg bid, and moxifloxacin 400 mg qd for 5–7 days) and 10 days moxifloxacin-based reverse sequential therapy as the first line treatment. Then we investigated the eradication rates of bismuth-containing quadruple therapy as the second line treatment. All subjects had no history of H. pylori eradication before. Eradication rates were described as intention-to-treat (ITT) and per-protocol (PP) analyses. H. pylori status was evaluated by 13 C-urea breath test 6 weeks after the end of the treatment. Moreover, we examined any side effects that caused discontinuation of therapy.
References
1. Kim SG, Jung HK, Lee HL, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. Korean J Gastroenterol. 2013; 62:3–26.
2. Gumurdulu Y, Serin E, Ozer B, et al. Low eradication rate of Helicobacter pylori with triple 7–14 days and quadriple therapy in Turkey. World J Gastroenterol. 2004; 10:668–671.
3. Graham DY, Shiotani A. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol. 2008; 5:321–331.
4. De Francesco V, Margiotta M, Zullo A, et al. Prevalence of primary clarithromycin resistance in Helicobacter pylori strains over a 15 year period in Italy. J Antimicrob Chemother. 2007; 59:783–785.
5. Gatta L, Vakil N, Leandro G, Di Mario F, Vaira D. Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and metaanalysis of randomized controlled trials in adults and children. Am J Gastroenterol. 2009; 104:3069–3079. quiz 1080.
6. Yoon H, Lee DH, Kim N, et al. Meta-analysis: is sequential therapy superior to standard triple therapy for Helicobacter pylori infection in Asian adults? J Gastroenterol Hepatol. 2013; 28:1801–1809.
7. Park HG, Jung MK, Jung JT, et al. Randomised clinical trial: a comparative study of 10-day sequential therapy with 7-day standard triple therapy for Helicobacter pylori infection in naïve patients. Aliment Pharmacol Ther. 2012; 35:56–65.
8. Kwon JH, Lee DH, Song BJ, et al. Ten-day sequential therapy as first-line treatment for Helicobacter pylori infection in Korea: a retrospective study. Helicobacter. 2010; 15:148–153.
9. Hwang JJ, Lee DH, Yoon H, Shin CM, Park YS, Kim N. Efficacy of moxifloxacin-based sequential and hybrid therapy for first-line Helicobacter pylori eradication. World J Gastroenterol. 2015; 21:10234–10241.
10. Tsay FW, Wu DC, Kao SS, et al. Reverse sequential therapy achieves a similar eradication rate as standard sequential therapy for Helicobacter pylori eradication: a randomized controlled trial. Helicobacter. 2015; 20:71–77.
11. Shaikh T, Fallone CA. Effectiveness of second through sixth line salvage Helicobacter pylori treatment: bismuth quadruple therapy is almost always a reasonable choice. Can J Gastroenterol Hepatol. 2016; 2016:7321574.
12. Chung JW, Lee JH, Jung HY, et al. Second-line Helicobacter pylori eradication: a randomized comparison of 1-week or 2-week bismuth-containing quadruple therapy. Helicobacter. 2011; 16:289–294.
13. Lee BH, Kim N, Hwang TJ, et al. Bismuth-containing quadruple therapy as second-line treatment for Helicobacter pylori infection: effect of treatment duration and antibiotic resistance on the eradication rate in Korea. Helicobacter. 2010; 15:38–45.
14. Cheon JH, Kim N, Lee DH, et al. Efficacy of moxifloxacin-based triple therapy as second-line treatment for Helicobacter pylori infection. Helicobacter. 2006; 11:46–51.
15. Lee JY, Kim N, Kim MS, et al. Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and anti-biotic resistance. Dig Dis Sci. 2014; 59:1235–1243.
16. Chuah SK, Tsay FW, Hsu PI, Wu DC. A new look at anti-Helicobacter pylori therapy. World J Gastroenterol. 2011; 17:3971–3975.
17. Perri F, Villani MR, Festa V, Quitadamo M, Andriulli A. Predictors of failure of Helicobacter pylori eradication with the standard ‘Maastricht triple therapy’. Aliment Pharmacol Ther. 2001; 15:1023–1029.
18. Basu PP, Rayapudi K, Pacana T, Shah NJ, Krishnaswamy N, Flynn M. A randomized study comparing levofloxacin, omeprazole, ni-tazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori. Am J Gastroenterol. 2011; 106:1970–1975.
19. Oh HS, Lee DH, Seo JY, et al. Ten-day sequential therapy is more effective than proton pump inhibitor-based therapy in Korea: a prospective, randomized study. J Gastroenterol Hepatol. 2012; 27:504–509.
20. Nishizawa T, Suzuki H, Suzuki M, Takahashi M, Hibi T. Proton pump inhibitor-amoxicillin-clarithromycin versus proton pump inhibitor-amoxicillin-metronidazole as first-line Helicobacter pylori eradication therapy. J Clin Biochem Nutr. 2012; 51:114–116.
21. Boyanova L, Mitov I. Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents. Expert Rev Anti Infect Ther. 2010; 8:59–70.
22. Lee JW, Kim N, Kim JM, et al. Prevalence of primary and secondary antimicrobial resistance of Helicobacter pylori in Korea from 2003 through 2012. Helicobacter. 2013; 18:206–214.
23. Gong EJ, Yun SC, Jung HY, et al. Meta-analysis of first-line triple therapy for helicobacter pylori eradication in Korea: is it time to change? J Korean Med Sci. 2014; 29:704–713.
24. Zullo A, De Francesco V, Hassan C, Morini S, Vaira D. The sequential therapy regimen for Helicobacter pylori eradication: a pooled-data analysis. Gut. 2007; 56:1353–1357.
25. Essa AS, Kramer JR, Graham DY, Treiber G. Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing "concomitant therapy" versus triple therapy for Helicobacter pylori eradication. Helicobacter. 2009; 14:109–118.
26. Kim JS, Kim BW, Ham JH, et al. Sequential therapy for Helicobacter pylori infection in Korea: systematic review and metaanalysis. Gut Liver. 2013; 7:546–551.
27. Keating GM, Scott LJ. Moxifloxacin: a review of its use in the management of bacterial infections. Drugs. 2004; 64:2347–2377.
28. Edlund C, Beyer G, Hiemer-Bau M, Ziege S, Lode H, Nord CE. Comparative effects of moxifloxacin and clarithromycin on the normal intestinal microflora. Scand J Infect Dis. 2000; 32:81–85.
29. Kale-Pradhan PB, Mihaescu A, Wilhelm SM. Fluoroquinolone sequential therapy for Helicobacter pylori: a metaanalysis. Pharmacotherapy. 2015; 35:719–730.
30. Hwang JJ, Lee DH, Lee AR, et al. Efficacy of moxifloxacin-based sequential therapy for first-line eradication of Helicobacter pylori infection in gastrointestinal disease. World J Gastroenterol. 2015; 21:5032–5038.
31. Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection–the Maastricht IV/Florence Consensus Report. Gut. 2012; 61:646–664.
32. Gisbert JP, Molina-Infante J, Marin AC, Vinagre G, Barrio J, McNicholl AG. Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple "sequential" or "concomitant" treatment to eradicate H. pylori infection. Scand J Gastroenterol. 2013; 48:652–656.
33. Perna F, Zullo A, Ricci C, Hassan C, Morini S, Vaira D. Levofloxacinbased triple therapy for Helicobacter pylori retreatment: role of bacterial resistance. Dig Liver Dis. 2007; 39:1001–1005.
34. Manfredi M, Bizzarri B, de'Angelis GL. Helicobacter pylori infection: sequential therapy followed by levofloxacin-containing triple therapy provides a good cumulative eradication rate. Helicobacter. 2012; 17:246–253.
35. Pontone S, Standoli M, Angelini R, Pontone P. Efficacy of H. pylori eradication with a sequential regimen followed by rescue therapy in clinical practice. Dig Liver Dis. 2010; 42:541–543.
36. Kim JM, Kim JS, Kim N, Kim SG, Jung HC, Song IS. Comparison of primary and secondary antimicrobial minimum inhibitory concentrations for Helicobacter pylori isolated from Korean patients. Int J Antimicrob Agents. 2006; 28:6–13.
37. Hwang JJ, Lee DH, Lee AR, et al. Fourteen- vs seven-day bismuth-based quadruple therapy for second-line Helicobacter pylori eradication. World J Gastroenterol. 2015; 21:8132–8139.
38. Muller N, Amiot A, Le Thuaut A, Bastuji-Garin S, Deforges L, Delchier JC. Rescue therapy with bismuth-containing quadruple therapy in patients infected with metronidazole-resistant Helicobacter pylori strains. Clin Res Hepatol Gastroenterol. 2016; 40:517–524.
39. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017; 112:212–239.
40. Venerito M, Krieger T, Ecker T, Leandro G, Malfertheiner P. Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy for empiric primary treatment of Helicobacter pylori infection. Digestion. 2013; 88:33–45.
Fig. 1.
Comparison of eradication rates according to the first line therapy. Eradication rates are presented by intention-to-treat (ITT) and per-protocol (PP) analyses. There was no statistically significant difference according to the first line therapy by both ITT (p-value= 0.257) and PP analyses (p-value=0.278). A, 10 days sequential; B, 14 days sequential; C, reverse sequential.
Table 1.
Baseline Characteristics of Enrolled Patients according to the First Line Therapy
| Variable | 10 days sequential (n=10) | 14 days sequential (n=5) | Reverse sequential (n=8) | p-value |
|---|---|---|---|---|
| Age | 63.50±1.59 | 59.4±3.36 | 61.0±2.95 | 0.125 |
| Sex | ||||
| Male | 6 (60) | 3 (60) | 2 (25) | 0.294 |
| Female | 4 (40) | 2 (40) | 6 (75) | 0.294 |
| Current smoker | 0 | 0 | 0 | |
| Alcohol consumption | 0 | 0 | 0 | |
| EGD findings | 0.052 | |||
| Gastritis | 9 (90) | 5 (100) | 7 (87.5) | |
| Duodenal ulcer | 1 (10) | 0 | 1 (12.5) | |
| Underlying diseases | ||||
| HTN | 4 (50) | 1 (12.5) | 3 (37.5) | 0.743 |
| DM | 1 (100) | 0 | 0 | >0.999 |
| Hyperlipidemia | 1 (50) | 0 | 1 (50) | >0.999 |
| Thyroid disease | 0 | 1 (50) | 1 (50) | 0.308 |
| Time interval (days) a | 67.42±43.56 | 63.86±36.23 | 77.40±64.07 | 0.125 |
| Second line treatment results | ||||
| Eradicated | 4 (40) | 4 (80) | 6 (75) | 0.257 |
| Not eradicated | 3 (30) | 0 | 2 (25) | 0.563 |
| Follow up loss | 3 (30) | 1 (20) | 0 | 0.298 |
Table 2.
Comparison of Eradicated and not Eradicated Groups
| Variable | Total (n=19) | Eradicated (n=14) | Not eradicated (n=5) | p-value |
|---|---|---|---|---|
| Age | 62.74±6.38 | 62.50±7.08 | 63.40±4.39 | 0.964 |
| Sex | ||||
| Male | 9 (47.4) | 7 (50) | 2 (40) | >0.99 |
| Female | 10 (52.6) | 7 (50) | 3 (60) | >0.99 |
| Current smoker | 0 | 0 | 0 | |
| Alcohol consumption | 0 | 0 | 0 | |
| EGD findings | 0.052 | |||
| Gastritis | 18 (94.7) | 18 (100) | 0 | |
| Duodenal ulcer | 1 (5.3) | 0 | 1 (100) | |
| Underlying diseases | ||||
| HTN | 7 (100) | 6 (85.7) | 1 (14.3) | 0.602 |
| Hyperlipidemia | 2 (100) | 1 (50) | 1 (50) | >0.999 |
| Thyroid disease | 1 (100) | 1 (100) | 0 | >0.999 |
| Time intervals (days)a | 67.42±43.56 | 63.86±36.23 | 77.40±64.07 | 0.964 |
| First line therapy regimen | 0.278 | |||
| 10 days sequential | 7 (36.8) | 4 (57.14) | 3 (42.86) | |
| 14 days sequential | 4 (21.1) | 4 (100) | 0 | |
| Reverse sequential | 8 (42.1) | 6 (75) | 2 (25) | |
| Adverse events b | ||||
| Nausea | 4 (21.1) | 3 (75) | 1 (25) | >0.999 |
| Epigastric soreness | 2 (10.5) | 2 (100) | 0 | 0.687 |
| Dyspepsia | 1 (5.3) | 1 (100) | 0 | 0.823 |
| Abdominal discomfort | 1 (5.3) | 0 | 1 (100) | 0.559 |
| Fatigue | 1 (5.3) | 0 | 1 (100) | 0.559 |
| Diarrhea | 1 (5.3) | 1 (100) | 0 | 0.823 |
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