Beyond Maastricht IV: are standard empiric triple therapies for Helicobacter pylori still useful in a South-European country?

BMC Gastroenterology

Carlos Sofia³  Carlos Calhau³  Alexandra Fernandes⁴  Carol Marinho¹  Maria Augusta Cipriano¹  Olga Cardoso²  Cristina Luxo²  José Manuel Romãozinho³  Maria Manuel Donato³  Nuno Almeida⁴ 

[1] Pathology Department, Coimbra University Hospital Centre, Praceta Mota Pinto e Avenida Bissaya Barreto, Coimbra, 3000-075, Portugal;Laboratory of Microbiology, Faculty of Pharmacy, Coimbra University, Azinhaga de Santa Comba, Coimbra, 3000-548, Portugal;Gastroenterology Centre, Faculty of Medicine, Coimbra University, Praceta Mota Pinto e Avenida Bissaya Barreto, Coimbra, 3000-075, Portugal;Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto e Avenida Bissaya Barreto, Coimbra, 3000-075, Portugal

关键词: Treatment failure;    Levofloxacin;    Helicobacter pylori;    Compliance;    Clarithromycin;   

Others  :  1137275
DOI  :  10.1186/s12876-015-0245-y

 received in 2014-07-17, accepted in 2015-02-02,  发布年份 2015

【 摘 要 】

Background

Empiric triple treatments for Helicobacter pylori (H. pylori) are increasingly unsuccessful. We evaluated factors associated with failure of these treatments in the central region of Portugal.

Methods

This single-center, prospective study included 154 patients with positive ¹³C-urea breath test (UBT). Patients with no previous H. pylori treatments (Group A, n = 103) received pantoprazole 40 mg 2×/day, amoxicillin 1000 mg 12/12 h and clarithromycin (CLARI) 500 mg 12/12 h, for 14 days. Patients with previous failed treatments (Group B, n = 51) and no history of levofloxacin (LVX) consumption were prescribed pantoprazole 40 mg 2×/day, amoxicillin 1000 mg 12/12 h and LVX 250 mg 12/12 h, for 10 days. H. pylori eradication was assessed by UBT 6–10 weeks after treatment. Compliance and adverse events were assessed by verbal and written questionnaires. Risk factors for eradication failure were determined by multivariate analysis.

Results

Intention-to-treat and per-protocol eradication rates were Group A: 68.9% (95% CI: 59.4–77.1%) and 68.8% (95% CI: 58.9–77.2%); Group B: 52.9% (95% CI: 39.5–66%) and 55.1% (95% CI: 41.3–68.2%), with 43.7% of Group A and 31.4% of Group B reporting adverse events. Main risk factors for failure were H. pylori resistance to CLARI and LVX in Groups A and B, respectively. Another independent risk factor in Group A was history of frequent infections (OR = 4.24; 95% CI 1.04–17.24). For patients with no H. pylori resistance to CLARI, a history of frequent infections (OR = 4.76; 95% CI 1.24–18.27) and active tobacco consumption (OR = 5.25; 95% CI 1.22–22.69) were also associated with eradication failure.

Conclusions

Empiric first and second-line triple treatments have unacceptable eradication rates in the central region of Portugal and cannot be used, according to Maastricht recommendations. Even for cases with no H. pylori resistance to the used antibiotics, results were unacceptable and, at least for CLARI, are influenced by history of frequent infections and tobacco consumption.

【 授权许可】

   
2015 Almeida et al.; licensee BioMed Central.

【 参考文献 】

• [1]Correa P, Piazuelo MB: Natural history of Helicobacter pylori infection. Dig Liver Dis 2008, 40(7):490-6.
• [2]Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, et al.: Management of Helicobacter pylori infection–the Maastricht IV/Florence Consensus Report. Gut 2012, 61(5):646-64.
• [3]Chuah SK, Tsay FW, Hsu PI, Wu DC: A new look at anti-Helicobacter pylori therapy. World J Gastroenterol 2011, 17(35):3971-5.
• [4]Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, et al.: Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007, 56(6):772-81.
• [5]Graham DY, Fischbach L: Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 2010, 59(8):1143-53.
• [6]Fischbach LA, Goodman KJ, Feldman M, Aragaki C: Sources of variation of Helicobacter pylori treatment success in adults worldwide: a meta-analysis. Int J Epidemiol 2002, 31(1):128-39.
• [7]Giorgio F, Principi M, De Francesco V, Zullo A, Losurdo G, Di Leo A, et al.: Primary clarithromycin resistance to Helicobacter pylori: is this the main reason for triple therapy failure? World J Gastrointest Pathophysiol 2013, 4(3):43-6.
• [8]Glupczynski Y, Megraud F, Lopez-Brea M, Andersen LP: European multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori. Eur J Clin Microbiol Infect Dis 2001, 20(11):820-3.
• [9]Megraud F, Coenen S, Versporten A, Kist M, Lopez-Brea M, Hirschl AM, et al.: Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 2013, 62(1):34-42.
• [10]Gisbert JP, Morena F: Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Aliment Pharmacol Ther 2006, 23(1):35-44.
• [11]Gisbert JP, Pajares JM: Helicobacter pylori “rescue” therapy after failure of two eradication treatments. Helicobacter 2005, 10(5):363-72.
• [12]Saad RJ, Schoenfeld P, Kim HM, Chey WD: Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis. Am J Gastroenterol 2006, 101(3):488-96.
• [13]Gatta L, Zullo A, Perna F, Ricci C, De Francesco V, Tampieri A, et al.: A 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses. Aliment Pharmacol Ther 2005, 22(1):45-9.
• [14]Sugimoto M, Yamaoka Y: Virulence factor genotypes of Helicobacter pylori affect cure rates of eradication therapy. Arch Immunol Ther Exp (Warsz) 2009, 57(1):45-56.
• [15]Bastos J, Peleteiro B, Barros R, Alves L, Severo M, de Fatima PM, et al.: Sociodemographic determinants of prevalence and incidence of Helicobacter pylori infection in Portuguese adults. Helicobacter 2013, 18(6):413-22.
• [16]de Boer WA, Thys JC, Borody TJ, Graham DY, O’Morain C, Tytgat GN: Proposal for use of a standard side effect scoring system in studies exploring Helicobacter pylori treatment regimens. Eur J Gastroenterol Hepatol 1996, 8(7):641-3.
• [17]Almeida N, Romaozinho JM, Donato MM, Luxo C, Cardoso O, Cipriano MA, et al.: Triple therapy with high-dose proton-pump inhibitor, amoxicillin, and doxycycline is useless for Helicobacter pylori eradication: a proof-of-concept study. Helicobacter 2014, 19(2):90-7.
• [18]Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL: Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori, association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 1995, 270(30):17771-7.
• [19]Santos A, Queiroz DM, Menard A, Marais A, Rocha GA, Oliveira CA, et al.: New pathogenicity marker found in the plasticity region of the Helicobacter pylori genome. J Clin Microbiol 2003, 41(4):1651-5.
• [20]Vakil N, Megraud F: Eradication therapy for Helicobacter pylori. Gastroenterology 2007, 133(3):985-1001.
• [21]Boyanova L, Mitov I: Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents. Expert Rev Anti Infect Ther 2010, 8(1):59-70.
• [22]De Francesco V, Giorgio F, Hassan C, Manes G, Vannella L, Panella C, et al.: Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis 2010, 19(4):409-14.
• [23]Graham DY, Fischbach LA: Empiric therapies for Helicobacter pylori infections. CMAJ 2011, 183(9):E506-8.
• [24]Fock KM, Katelaris P, Sugano K, Ang TL, Hunt R, Talley NJ, et al.: Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol 2009, 24(10):1587-600.
• [25]Gisbert JP: Rescue therapy for Helicobacter pylori infection 2012. Gastroenterol Res Pract. 2012, 2012:974594.
• [26]Gisbert JP: “Rescue” regimens after Helicobacter pylori treatment failure. World J Gastroenterol. 2008, 14(35):5385-402.
• [27]Gisbert JP, Gisbert JL, Marcos S, Jimenez-Alonso I, Moreno-Otero R, Pajares JM: Empirical rescue therapy after Helicobacter pylori treatment failure: a 10-year single-centre study of 500 patients. Aliment Pharmacol Ther 2008, 27(4):346-54.
• [28]Graham DY, Shiotani A: New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol 2008, 5(6):321-31.
• [29]Gastrenterologia SPd: Normas de orientação clínica - helicobacter pylori GE - Jornal Português de Gastrenterologia 2008, 15:192-4.
• [30]Cabrita J, Oleastro M, Matos R, Manhente A, Cabral J, Barros R, et al.: Features and trends in Helicobacter pylori antibiotic resistance in Lisbon area, Portugal (1990–1999). J Antimicrob Chemother 2000, 46(6):1029-31.
• [31]Cerqueira RM, Correia MR, Fernandes CD, Vilar H, Manso MC: Cumulative Helicobacter pylori eradication therapy in obese patients undergoing gastric bypass surgery. Obes Surg 2013, 23(2):145-9.
• [32]Adriaenssens N, Coenen S, Versporten A, Muller A, Minalu G, Faes C, et al.: European surveillance of antimicrobial consumption (ESAC): outpatient antibiotic use in Europe (1997–2009). J Antimicrob Chemother 2011, 66 Suppl 6:vi3-vi12.
• [33]Oleastro M, Pelerito A, Nogueira P, Benoliel J, Santos A, Cabral J, et al.: Prevalence and incidence of Helicobacter pylori Infection in a healthy pediatric population in the Lisbon area. Helicobacter 2011, 16(5):363-72.
• [34]Kim JJ, Kim JG, Kwon DH: Mixed-infection of antibiotic susceptible and resistant Helicobacter pylori isolates in a single patient and underestimation of antimicrobial susceptibility testing. Helicobacter 2003, 8(3):202-6.
• [35]Van Doorn LJ, Figueiredo C, Megraud F, Pena S, Midolo P, Queiroz DM, et al.: Geographic distribution of vacA allelic types of Helicobacter pylori. Gastroenterology 1999, 116(4):823-30.
• [36]Kanizaj TF, Kunac N: Helicobacter pylori: future perspectives in therapy reflecting three decades of experience. World J Gastroenterol 2014, 20(3):699-705.
• [37]De Francesco V, Zullo A, Giorgio F, Saracino I, Zaccaro C, Hassan C, et al.: Change of point mutations in Helicobacter pylori rRNA associated with clarithromycin resistance in Italy. J Med Microbiol 2014, 63(Pt 3):453-7.
• [38]Suzuki T, Matsuo K, Ito H, Sawaki A, Hirose K, Wakai K, et al.: Smoking increases the treatment failure for Helicobacter pylori eradication. Am J Med 2006, 119(3):217-24.
• [39]Gerrits MM, van Vliet AH, Kuipers EJ, Kusters JG: Helicobacter pylori and antimicrobial resistance: molecular mechanisms and clinical implications. Lancet Infect Dis 2006, 6(11):699-709.
• [40]Han SR, Bhakdi S, Maeurer MJ, Schneider T, Gehring S: Stable and unstable amoxicillin resistance in Helicobacter pylori: should antibiotic resistance testing be performed prior to eradication therapy? J Clin Microbiol 1999, 37(8):2740-1.
• [41]Agudo S, Perez-Perez G, Alarcon T, Lopez-Brea M: High prevalence of clarithromycin-resistant Helicobacter pylori strains and risk factors associated with resistance in Madrid. Spain J Clin Microbiol 2010, 48(10):3703-7.
• [42]van Doorn LJ, Schneeberger PM, Nouhan N, Plaisier AP, Quint WG, de Boer WA: Importance of Helicobacter pylori cagA and vacA status for the efficacy of antibiotic treatment. Gut 2000, 46(3):321-6.
• [43]Miehlke S, Hansky K, Schneider-Brachert W, Kirsch C, Morgner A, Madisch A, et al.: Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Aliment Pharmacol Ther 2006, 24(2):395-403.
• [44]Shirai N, Sugimoto M, Kodaira C, Nishino M, Ikuma M, Kajimura M, et al.: Dual therapy with high doses of rabeprazole and amoxicillin versus triple therapy with rabeprazole, amoxicillin, and metronidazole as a rescue regimen for Helicobacter pylori infection after the standard triple therapy. Eur J Clin Pharmacol 2007, 63(8):743-9.
• [45]Broutet N, Tchamgoue S, Pereira E, Lamouliatte H, Salamon R, Megraud F: Risk factors for failure of Helicobacter pylori therapy–results of an individual data analysis of 2751 patients. Aliment Pharmacol Ther 2003, 17(1):99-109.
• [46]Wolle K, Malfertheiner P: Treatment of Helicobacter pylori. Best Pract Res Clin Gastroenterol 2007, 21(2):315-24.
• [47]Schmulson M, Adeyemo M, Gutierrez-Reyes G, Charua-Guindic L, Farfan-Labonne B, Ostrosky-Solis F, et al.: Differences in gastrointestinal symptoms according to gender in Rome II positive IBS and dyspepsia in a Latin American population. Am J Gastroenterol 2010, 105(4):925-32.
• [48]Graham DY: Efficient identification and evaluation of effective Helicobacter pylori therapies. Clin Gastroenterol Hepatol 2009, 7(2):145-8.
• [49]Tai WC, Chiu CH, Liang CM, Chang KC, Kuo CM, Chiu YC, et al.: Ten-Day versus 14-Day levofloxacin-containing triple therapy for second-line anti-Helicobacter pylori Eradication in Taiwan. Gastroenterol Res Pract. 2013, 2013:932478.
• [50]Gisbert JP, Perez-Aisa A, Bermejo F, Castro-Fernandez M, Almela P, Barrio J, et al.: Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients. J Clin Gastroenterol 2013, 47(2):130-5.
• [51]De Francesco V, Hassan C, Ridola L, Giorgio F, Ierardi E, Zullo A: Sequential, concomitant and hybrid first-line therapies for Helicobacter pylori eradication: a prospective randomized study. J Med Microbiol 2014, 63(Pt 5):748-52.