title: Treatment of Helicobacter pylori infection: meeting the challenge of antimicrobial resistance.
abstract: Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders including peptic ulcer disease and gastric cancer. Due to the wide increase in prevalence of H. pylori resistance to antibiotics, clarithromycin-based triple therapies are not any more suitable for unconditional empiric use, and should not be recommended, unless local resistance to this antibiotic is low (< 20%). Alternative strategies have been proposed to overcome the issue of increasing clarithromycin resistance, and some of them are already implemented in clinical practice. These comprise: (1) adoption of novel, more effective, empirical treatments: bismuth quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens, the latter mainly designated as second-line/rescue options; (2) perspectives for a susceptibility-guided (tailored) therapeutic approach based on culture-free molecular testing methods; and (3) adjunct use of probiotics to improve eradication rates. The present article is aimed to provide a comprehensive overview of current and emerging strategies in the treatment of H. pylori infection, focusing on the challenge of antimicrobial resistance.
authors.affiliation: Vasilios Papastergiou, Stylianos Karatapanis, Department of Internal Medicine, General Hospital of Rhodes, 85100 Rhodes, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Papastergiou
authors.affiliation: Vasilios Papastergiou, Stylianos Karatapanis, Department of Internal Medicine, General Hospital of Rhodes, 85100 Rhodes, Greece.
authors.forename: Sotirios D
authors.initials: SD
authors.lastname: Georgopoulos
authors.affiliation: Vasilios Papastergiou, Stylianos Karatapanis, Department of Internal Medicine, General Hospital of Rhodes, 85100 Rhodes, Greece.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Karatapanis
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004359:Drug Therapy, Combination; D005838:Genotype; D016481:Helicobacter Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D018579:Patient Selection; D010597:Pharmacogenetics; D011237:Predictive Value of Tests; D019936:Probiotics / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors
keywords: Antibiotic resistance; Bismuth-quadruple; Concomitant; Helicobacter pylori; Sequential
references.citation: J Clin Microbiol. 2009 Nov;47(11):3600-7
references.pmid: 19759218
references.citation: Clin Pharmacol Ther. 2001 Mar;69(3):158-68
references.pmid: 11240980
references.citation: Clin Gastroenterol Hepatol. 2010 Jan;8(1):36-41.e1
references.pmid: 19804842
references.citation: Aliment Pharmacol Ther. 2001 Mar;15(3):417-21
references.pmid: 11207518
references.citation: J Gastroenterol Hepatol. 2008 Dec;23 Suppl 2:S171-4
references.pmid: 19120893
references.citation: Clin Exp Gastroenterol. 2012;5:23-34
references.pmid: 22457599
references.citation: Lancet. 2009 Oct 24;374(9699):1449-61
references.pmid: 19683340
references.citation: Intern Med. 2010;49(12):1103-9
references.pmid: 20558925
references.citation: Gastroenterology. 2013 Jul;145(1):121-128.e1
references.pmid: 23562754
references.citation: Lancet. 2011 Aug 6;378(9790):507-14
references.pmid: 21777974
references.citation: Clin Pharmacol Ther. 2006 Jan;79(1):103-13
references.pmid: 16413245
references.citation: Am J Gastroenterol. 2003 Mar;98(3):562-7
references.pmid: 12650788
references.citation: Helicobacter. 2011 Apr;16(2):139-45
references.pmid: 21435092
references.citation: J Clin Microbiol. 2004 Oct;42(10):4512-8
references.pmid: 15472302
references.citation: Antimicrob Agents Chemother. 2009 Jul;53(7):3097-9
references.pmid: 19380599
references.citation: Helicobacter. 2012 Aug;17(4):246-53
references.pmid: 22759323
references.citation: J Gastroenterol Hepatol. 2010 May;25 Suppl 1:S75-9
references.pmid: 20586871
references.citation: Aliment Pharmacol Ther. 2010 Nov;32(9):1069-79
references.pmid: 21039671
references.citation: Helicobacter. 2014 Feb;19(1):74-9
references.pmid: 24033865
references.citation: Aliment Pharmacol Ther. 2004 Nov 15;20(10):1071-82
references.pmid: 15569109
references.citation: Gastroenterology. 1996 Aug;111(2):358-67
references.pmid: 8690200
references.citation: Gut. 2010 Aug;59(8):1143-53
references.pmid: 20525969
references.citation: J Gastrointestin Liver Dis. 2010 Dec;19(4):409-14
references.pmid: 21188333
references.citation: J Clin Gastroenterol. 2013 Jan;47(1):21-4
references.pmid: 22647826
references.citation: Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):29-41
references.pmid: 19968574
references.citation: World J Gastroenterol. 2012 Oct 28;18(40):5669-78
references.pmid: 23155306
references.citation: BMJ. 2013 Aug 07;347:f4587
references.pmid: 23926315
references.citation: Gastroenterology. 2012 Jul;143(1):55-61.e1; quize e13-4
references.pmid: 22484118
references.citation: J Antimicrob Chemother. 2010 Feb;65(2):327-32
references.pmid: 20008044
references.citation: J Med Microbiol. 2012 Jan;61(Pt 1):85-93
references.pmid: 21873378
references.citation: Helicobacter. 2012 Aug;17(4):269-76
references.pmid: 22759326
references.citation: J Clin Gastroenterol. 2010 May-Jun;44(5):313-25
references.pmid: 20054285
references.citation: World J Gastroenterol. 2012 Nov 21;18(43):6302-7
references.pmid: 23180952
references.citation: World J Gastroenterol. 2012 Nov 21;18(43):6250-4
references.pmid: 23180945
references.citation: Intern Med. 2009;48(24):2069-76
references.pmid: 20009394
references.citation: Helicobacter. 2008 Dec;13(6):532-41
references.pmid: 19166419
references.citation: Helicobacter. 2006 Oct;11(5):441-5
references.pmid: 16961806
references.citation: Aliment Pharmacol Ther. 2012 Jan;35(2):209-21
references.pmid: 22129228
references.citation: Helicobacter. 1998 Mar;3(1):54-8
references.pmid: 9546119
references.citation: Antimicrob Agents Chemother. 2009 Apr;53(4):1720-1
references.pmid: 19188389
references.citation: Helicobacter. 2011 Apr;16(2):146-52
references.pmid: 21435093
references.citation: Clin Gastroenterol Hepatol. 2013 Jul;11(7):802-7.e1
references.pmid: 23376004
references.citation: Scand J Gastroenterol. 2013 Jun;48(6):652-6
references.pmid: 23556551
references.citation: Aliment Pharmacol Ther. 1999 Aug;13(8):1047-55
references.pmid: 10468680
references.citation: J Gastroenterol Hepatol. 2013 Dec;28(12):1801-9
references.pmid: 24118110
references.citation: J Clin Gastroenterol. 2014 Mar;48(3):241-7
references.pmid: 24002127
references.citation: Aliment Pharmacol Ther. 2003 Mar 1;17(5):719-26
references.pmid: 12641522
references.citation: J Clin Pharm Ther. 2009 Feb;34(1):41-53
references.pmid: 19125902
references.citation: Gut. 2013 Jan;62(1):34-42
references.pmid: 22580412
references.citation: Clin Pharmacol Ther. 2007 Apr;81(4):521-8
references.pmid: 17215846
references.citation: Am J Gastroenterol. 2009 Dec;104(12):3069-79; quiz 1080
references.pmid: 19844205
references.citation: World J Gastroenterol. 2007 Feb 7;13(5):671-5
references.pmid: 17278188
references.citation: Intern Med. 2008;47(12):1077-83
references.pmid: 18552463
references.citation: Digestion. 2006;74(1):42-6
references.pmid: 17068397
references.citation: Antimicrob Agents Chemother. 1997 Dec;41(12):2621-8
references.pmid: 9420030
references.citation: Gut. 2010 Nov;59(11):1465-70
references.pmid: 20947881
references.citation: Eur J Gastroenterol Hepatol. 2000 Dec;12(12):1315-8
references.pmid: 11192320
references.citation: Eur J Clin Microbiol Infect Dis. 1989 Oct;8(10):888-9
references.pmid: 2512133
references.citation: Helicobacter. 2013 Jun;18(3):180-6
references.pmid: 23305083
references.citation: Helicobacter. 2012 Aug;17(4):254-63
references.pmid: 22759324
references.citation: Dig Dis Sci. 2014 Feb;59(2):383-9
references.pmid: 24126798
references.citation: Helicobacter. 2013 Apr;18(2):129-34
references.pmid: 23121338
references.citation: Dig Dis Sci. 2000 Jan;45(1):63-7
references.pmid: 10695615
references.citation: Helicobacter. 2010 Oct;15(5):460-6
references.pmid: 21083752
references.citation: Gastroenterology. 2002 Dec;123(6):1763-9
references.pmid: 12454831
references.citation: Am J Gastroenterol. 2010 Jan;105(1):65-73
references.pmid: 19755966
references.citation: J Antimicrob Chemother. 2003 Jan;51(1):9-11
references.pmid: 12493781
references.citation: BMC Gastroenterol. 2013 Mar 26;13:56
references.pmid: 23530767
references.citation: Aliment Pharmacol Ther. 2004 Jul 1;20(1):99-107
references.pmid: 15225176
references.citation: Digestion. 2011;84(4):299-305
references.pmid: 22057261
references.citation: Aliment Pharmacol Ther. 1997 Apr;11 Suppl 1:71-88
references.pmid: 9146793
references.citation: World J Gastroenterol. 2008 Dec 28;14(48):7361-70
references.pmid: 19109870
references.citation: Clin Ther. 2010 Nov;32(12):2003-11
references.pmid: 21118735
references.citation: Therap Adv Gastroenterol. 2011 Mar;4(2):103-14
references.pmid: 21694812
references.citation: Ann Clin Microbiol Antimicrob. 2013 Jan 08;12:3
references.pmid: 23298145
references.citation: Helicobacter. 2009 Oct;14(5):97-107
references.pmid: 19751434
references.citation: J Antimicrob Chemother. 1999 Apr;43(4):511-5
references.pmid: 10350380
references.citation: Helicobacter. 2013 Aug;18(4):280-4
references.pmid: 23433200
references.citation: Helicobacter. 2012 Sep;17 Suppl 1:49-55
references.pmid: 22958156
references.citation: Int J Antimicrob Agents. 2001 Jan;17(1):39-44
references.pmid: 11137647
references.citation: J Med Microbiol. 2004 Nov;53(Pt 11):1123-1128
references.pmid: 15496391
references.citation: Gut. 2007 Nov;56(11):1502
references.pmid: 17938430
references.citation: Clin Res Hepatol Gastroenterol. 2013 Dec;37(6):647-50
references.pmid: 23747131
references.citation: Helicobacter. 2009 Apr;14(2):109-18
references.pmid: 19298338
references.citation: J Gastroenterol Hepatol. 2009 Oct;24(10):1587-600
references.pmid: 19788600
references.citation: J Dig Dis. 2010 Oct;11(5):313-8
references.pmid: 20883428
references.citation: Aliment Pharmacol Ther. 2006 Jan 1;23(1):35-44
references.pmid: 16393278
references.citation: Aliment Pharmacol Ther. 2002 Mar;16(3):569-75
references.pmid: 11876712
references.citation: Afr Health Sci. 2007 Sep;7(3):143-7
references.pmid: 18052867
references.citation: Helicobacter. 2011 Apr;16(2):131-8
references.pmid: 21435091
references.citation: J Clin Gastroenterol. 2013 Mar;47(3):228-32
references.pmid: 22858517
references.citation: Helicobacter. 2004;9 Suppl 1:67-72
references.pmid: 15347308
references.citation: Med J Aust. 1987 Apr 20;146(8):450-1
references.pmid: 3614058
references.citation: Gut. 2004 Sep;53(9):1374-84
references.pmid: 15306603
references.citation: Ann Intern Med. 2008 Jun 17;148(12):923-31
references.pmid: 18490667
references.citation: Helicobacter. 2009 Oct;14(5):86-90
references.pmid: 19751432
references.citation: J Clin Gastroenterol. 2013 Jan;47(1):25-32
references.pmid: 23090045
references.citation: Helicobacter. 2012 Feb;17(1):49-53
references.pmid: 22221616
references.citation: Helicobacter. 2007 Apr;12(2):136-41
references.pmid: 17309750
references.citation: Helicobacter. 2000 Jun;5(2):88-93
references.pmid: 10849057
references.citation: Semin Cancer Biol. 2013 Dec;23(6 Pt B):492-501
references.pmid: 23876852
references.citation: Gut. 2007 Jun;56(6):772-81
references.pmid: 17170018
references.citation: J Infect Dis. 2013 Oct 1;208(7):1123-30
references.pmid: 23801607
references.citation: Lancet. 2013 Jan 19;381(9862):205-13
references.pmid: 23158886
references.citation: Gut. 2014 Feb;63(2):244-9
references.pmid: 23665990
references.citation: Helicobacter. 2013 Dec;18(6):459-67
references.pmid: 23714140
references.citation: J Clin Gastroenterol. 2013 Feb;47(2):130-5
references.pmid: 22647827
references.citation: Ann Pharmacother. 2011 Jul;45(7-8):960-6
references.pmid: 21693698
references.citation: Intern Med. 2011;50(21):2717; author reply 2719-20
references.pmid: 22041399
references.citation: World J Gastroenterol. 2010 May 14;16(18):2272-7
references.pmid: 20458765
references.citation: J Gastrointestin Liver Dis. 2011 Sep;20(3):235-9
references.pmid: 21961089
references.citation: Expert Rev Anti Infect Ther. 2010 Jan;8(1):59-70
references.pmid: 20014902
references.citation: Clin Infect Dis. 2007 Jan 15;44(2):e5-8
references.pmid: 17173210
references.citation: Expert Opin Investig Drugs. 2001 Aug;10(8):1559-66
references.pmid: 11772270
references.citation: BMC Gastroenterol. 2011 Oct 17;11:112
references.pmid: 22004003
references.citation: FEMS Immunol Med Microbiol. 2003 May 25;36(3):193-8
references.pmid: 12738391
references.citation: J Clin Pharm Ther. 2010 Jun;35(3):343-50
references.pmid: 20831535
references.citation: J Dig Dis. 2012 Jan;13(1):54-9
references.pmid: 22188917
references.citation: Curr Pharm Des. 2000 Oct;6(15):1537-44
references.pmid: 10974150
references.citation: Am J Gastroenterol. 2007 Aug;102(8):1808-25
references.pmid: 17608775
references.citation: Helicobacter. 2007 Aug;12(4):275-8
references.pmid: 17669098
references.citation: Digestion. 2013;88(1):33-45
references.pmid: 23880479
references.citation: Am J Gastroenterol. 2006 Mar;101(3):488-96
references.pmid: 16542284
references.citation: Ir J Med Sci. 2013 Dec;182(4):693-5
references.pmid: 23625165
references.citation: J Gastroenterol. 1998 Oct;33(5):640-5
references.pmid: 9773927
references.citation: Gastroenterol Res Pract. 2012;2012:740381
references.pmid: 22690211
references.citation: Int J Hematol. 2013 Jun;97(6):735-42
references.pmid: 23616223
references.citation: Clin Gastroenterol Hepatol. 2005 Jun;3(6):564-73
references.pmid: 15952098
references.citation: J Nutr. 2007 Mar;137(3 Suppl 2):812S-8S
references.pmid: 17311980
references.citation: Lancet. 2011 Mar 12;377(9769):905-13
references.pmid: 21345487
references.citation: Clin Microbiol Rev. 2007 Apr;20(2):280-322
references.pmid: 17428887
references.citation: J Antimicrob Chemother. 2013 Jan;68(1):222-8
references.pmid: 22984204
references.citation: Aliment Pharmacol Ther. 2007 Aug 1;26(3):343-57
references.pmid: 17635369
references.citation: Helicobacter. 2005 Feb;10(1):1-3
references.pmid: 15691309
references.citation: Antimicrob Agents Chemother. 1996 Feb;40(2):477-80
references.pmid: 8834903
references.citation: Gut. 2007 Oct;56(10):1353-7
references.pmid: 17566020
references.citation: Dig Liver Dis. 2009 Jul;41(7):480-5
references.pmid: 18974025
references.citation: Nat Rev Gastroenterol Hepatol. 2011 Feb;8(2):79-88
references.pmid: 21293508
references.citation: Dig Liver Dis. 2013 Jan;45(1):18-22
references.pmid: 23022424
references.citation: Dig Liver Dis. 2009 Aug;41(8):610-1
references.pmid: 19200790
references.citation: J Clin Microbiol. 2007 Jun;45(6):1718-22
references.pmid: 17392440
references.citation: Aliment Pharmacol Ther. 2002 Feb;16(2):167-80
references.pmid: 11860399
references.citation: J Clin Gastroenterol. 2013 May-Jun;47(5):383-8
references.pmid: 23388847
references.citation: Helicobacter. 2002 Apr;7(2):99-104
references.pmid: 11966868
references.citation: Gut. 2012 May;61(5):646-64
references.pmid: 22491499
references.citation: Gastroenterol Res Pract. 2012;2012:974594
references.pmid: 22536225
references.citation: J Clin Microbiol. 2005 Jul;43(7):3494-6
references.pmid: 16000488
references.citation: Aliment Pharmacol Ther. 2012 Apr;35(8):941-7
references.pmid: 22372560
references.citation: Helicobacter. 1999 Sep;4(3):204-10
references.pmid: 10469195
references.citation: Helicobacter. 2011 Oct;16(5):410-4
references.pmid: 21923688