Association of a probiotic to a Helicobacter pylori eradication regimen does not increase efficacy or decreases the adverse effects of the treatment: a prospective, randomized, double-blind, placebo-controlled study

BMC Gastroenterology

Jaime Natan Eisig¹  Décio Chinzon¹  Cristina S Bogsan¹  Maricê Nogueira de Oliveira¹  Joaquim Prado Moraes-Filho¹  Rejane Mattar¹  Ricardo Correa Barbuti¹  Fernando Marcuz Silva¹  Tomás Navarro-Rodriguez¹ 

[1]Serviço de Gastroenterologia Clínica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 255 – Cerqueira Cezar, São Paulo, SP, Brasil

关键词: Adverse effects;    Treatment efficacy;    Functional dyspepsia;    Peptic ulcer;    Furazolidone;    Tetracycline;    Probiotic;    Helicobacter pylori eradication;   

Others  :  858105
DOI  :  10.1186/1471-230X-13-56

 received in 2012-06-26, accepted in 2013-03-19,  发布年份 2013

【 摘 要 】

Background

The treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy.

If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen.

Methods

Patients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment.

Results

One hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p = 0.49); per intention to treat, 81.8% and 79.6%, respectively (p = 0.53). The rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2% with placebo (p = 0.20). At 30 days, it was 44.9% and 60.4%, respectively (p = 0.08).

Conclusions

The use of this probiotic compound compared to placebo in the proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia showed no significant difference in efficacy or adverse effects.

Trial registration

Current Controlled Trials ISRCTN04714018

【 授权许可】

   
2013 Navarro-Rodriguez et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Coelho LG, Zaterka S: [Second Brazilian Consensus Conference on Helicobacter pylori infection]. Arq Gastroenterol 2005, 42:128-132.
• [2]Chey WD, Wong BC: American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007, 102:1808-1825.
• [3]Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, El-Omar EM, Kuipers EJ: Management of Helicobacter pylori infection–the Maastricht IV/ Florence Consensus Report. Gut 2012, 61:646-664.
• [4]Talley NJ, Fock KM, Moayyedi P: Gastric Cancer Consensus conference recommends Helicobacter pylori screening and treatment in asymptomatic persons from high-risk populations to prevent gastric cancer. Am J Gastroenterol 2008, 103:510-514.
• [5]Gasparetto M, Pescarin M, Guariso G: Helicobacter pylori Eradication Therapy: Current Availabilities. ISRN Gastroenterol 2012, 2012:186734.
• [6]Cutler AF, Schubert TT: Patient factors affecting Helicobacter pylori eradication with triple therapy. Am J Gastroenterol 1993, 88:505-509.
• [7]Qua CS, Manikam J, Goh KL: Efficacy of 1-week proton pump inhibitor triple therapy as first-line Helicobacter pylori eradication regime in Asian patients: is it still effective 10 years on? J Dig Dis 2010, 11:244-248.
• [8]Periti P, Mazzei T, Mini E, Novelli A: Adverse effects of macrolide antibacterials. Drug Saf 1993, 9:346-364.
• [9]Salvo F, Polimeni G, Moretti U, Conforti A, Leone R, Leoni O, Motola D, Dusi G, Caputi AP: Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy. J Antimicrob Chemother 2007, 60:121-126.
• [10]Porras C, Nodora J, Sexton R, Ferreccio C, Jimenez S, Dominguez RL, Cook P, Anderson G, Morgan DR, Baker LH, Greenberg ER, Herrero R: Epidemiology of Helicobacter pylori infection in six Latin American countries (SWOG Trial S0701). Cancer Causes Control 2012. Available at http://link.springer.com/content/pdf/10.1007%2Fs10552-012-0117-5 webcite
• [11]Zaterka S, Eisig JN, Chinzon D, Rothstein W: Factors related to Helicobacter pylori prevalence in an adult population in Brazil. Helicobacter 2007, 12:82-88.
• [12]Escobar-Pardo ML, de Godoy AP, Machado RS, Rodrigues D, Fagundes Neto U, Kawakami E: Prevalence of Helicobacter pylori infection and intestinal parasitosis in children of the Xingu Indian Reservation. J Pediatr (Rio J) 2011, 87:393-398.
• [13]Miranda AC, Machado RS, Silva EM, Kawakami E: Seroprevalence of Helicobacter pylori infection among children of low socioeconomic level in Sao Paulo. Sao Paulo Med J 2010, 128:187-191.
• [14]Dattoli VC, Veiga RV, da Cunha SS, Pontes-de-Carvalho LC, Barreto ML, Alcantara-Neves NM: Seroprevalence and potential risk factors for Helicobacter pylori infection in Brazilian children. Helicobacter 2010, 15:273-278.
• [15]Rodrigues MN, Queiroz DM, Rodrigues RT, Rocha AM, Braga Neto MB, Braga LL: Helicobacter pylori infection in adults from a poor urban community in northeastern Brazil: demographic, lifestyle and environmental factors. Braz J Infect Dis 2005, 9:405-410.
• [16]Rodrigues MN, Queiroz DM, Rodrigues RT, Rocha AM, Luz CR, Braga LL: Prevalence of Helicobacter pylori infection in Fortaleza, Northeastern Brazil. Rev Saude Publica 2005, 39:847-849.
• [17]Almeida Cunha RP, Alves FP, Rocha AM, Rocha GA, Camargo LM, Nogueira PO, Camargo EP, Queiroz DM: Prevalence and risk factors associated with Helicobacter pylori infection in native populations from Brazilian Western Amazon. Trans R Soc Trop Med Hyg 2003, 97:382-386.
• [18]Prazeres Magalhaes P, De Magalhaes Queiroz DM, Campos Barbosa DV, Aguiar Rocha G, Nogueira Mendes E, Santos A, Valle Correa PR, Camargos Rocha AM, Martins Teixeira L, Affonso de Oliveira C: Helicobacter pylori primary resistance to metronidazole and clarithromycin in Brazil. Antimicrob Agents Chemother 2002, 46:2021-2023.
• [19]Oleastro M, Cabral J, Ramalho PM, Lemos PS, Paixao E, Benoliel J, Santos A, Lopes AI: Primary antibiotic resistance of Helicobacter pylori strains isolated from Portuguese children: a prospective multicentre study over a 10 year period. J Antimicrob Chemother 2011, 66:2308-2311.
• [20]Goh KL, Navaratnam P: High Helicobacter pylori resistance to metronidazole but zero or low resistance to clarithromycin, levofloxacin, and other antibiotics in Malaysia. Helicobacter 2011, 16:241-245.
• [21]De Francesco V, Giorgio F, Hassan C, Manes G, Vannella L, Panella C, Ierardi E, Zullo A: Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis 2010, 19:409-414.
• [22]Mendonca S, Ecclissato C, Sartori MS, Godoy AP, Guerzoni RA, Degger M, Pedrazzoli J Jr: Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone in Brazil. Helicobacter 2000, 5:79-83.
• [23]Godoy AP, Ribeiro ML, Benvengo YH, Vitiello L, Miranda Mde C, Mendonca S, Pedrazzoli J Jr: Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates. BMC Gastroenterol 2003, 3:20. BioMed Central Full Text
• [24]Felga G, Silva FM, Barbuti RC, Navarro-Rodriguez T, Zaterka S, Eisig JN: Clarithromycin-based triple therapy for Helicobacter pylori treatment in peptic ulcer patients. J Infect Dev Ctries 2010, 4:712-716.
• [25]Silva FM, Eisig JN, Chehter EZ, Silva JJ, Laudanna AA: Omeprazole, furazolidone, and tetracycline: an eradication treatment for resistant H. pylori in Brazilian patients with peptic ulcer disease. Rev Hosp Clin Fac Med Sao Paulo 2002, 57:205-208.
• [26]Glupczynski Y, Burette A: Drug therapy for Helicobacter pylori infection: problems and pitfalls. Am J Gastroenterol 1990, 85:1545-1551.
• [27]Peitz U, Sulliga M, Wolle K, Leodolter A, Von Arnim U, Kahl S, Stolte M, Borsch G, Labenz J, Malfertheiner P: High rate of post-therapeutic resistance after failure of macrolide-nitroimidazole triple therapy to cure Helicobacter pylori infection: impact of two second-line therapies in a randomized study. Aliment Pharmacol Ther 2002, 16:315-324.
• [28]Selgrad M, Malfertheiner P: Treatment of Helicobacter pylori. Curr Opin Gastroenterol 2011, 27:565-570.
• [29]Pérez-Cobas AE, Gosalbes MJ, Friedrichs A, Knecht H, Artacho A, Eismann K, Otto W, Rojo D, Bargiela R, von Bergen M, Neulinger SC, Däumer C, Heinsen FA, Latorre A, Barbas C, Seifert J, Dos Santos VM, Ott SJ, Ferrer M, Moya A: Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut 2012. Available at http://gut.bmj.com/content/early/2012/12/11/gutjnl-2012-303184.long webcite
• [30]Danese S, Armuzzi A, Romano A, Cremonini F, Candelli M, Franceschi F, Ojetti V, Venuti A, Pola P, Gasbarrini G: Efficacy and tolerability of antibiotics in patients undergoing H. pylori eradication. Hepatogastroenterology 2001, 48:465-467.
• [31]Armuzzi A, Cremonini F, Bartolozzi F, Canducci F, Candelli M, Ojetti V, Cammarota G, Anti M, De Lorenzo A, Pola P: The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther 2001, 15:163-169.
• [32]Cremonini F, Di Caro S, Covino M, Armuzzi A, Gabrielli M, Santarelli L, Nista EC, Cammarota G, Gasbarrini G, Gasbarrini A: Effect of different probiotic preparations on anti-Helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study. Am J Gastroenterol 2002, 97:2744-2749.
• [33]Wilhelm SM, Johnson JL, Kale-Pradhan PB: Treating bugs with bugs: the role of probiotics as adjunctive therapy for Helicobacter pylori. Ann Pharmacother 2011, 45:960-966.
• [34]Yasar B, Abut E, Kayadibi H, Toros B, Sezikli M, Akkan Z, Keskin O, Ovunc Kurdas O: Efficacy of probiotics in Helicobacter pylori eradication therapy. Turk J Gastroenterol 2011, 21:212-217.
• [35]Yang YJ, Sheu BS: Probiotics-containing yogurts suppress Helicobacter pylori load and modify immune response and intestinal microbiota in the Helicobacter pylori-infected children. Helicobacter 2012, 17:297-304.
• [36]Zhou C, Ma FZ, Deng XJ, Yuan H, Ma HS: Lactobacilli inhibit interleukin-8 production induced by Helicobacter pylori lipopolysaccharide-activated Toll-like receptor 4. World J Gastroenterol 2008, 14:5090-5095.
• [37]Hsieh PS, Tsai YC, Chen YC, Teh SF, Ou CM, King VA: Eradication of Helicobacter pylori infection by the probiotic strains Lactobacillus johnsonii MH-68 and L. salivarius ssp. salicinius AP-32. Helicobacter 2012, 17:466-477.
• [38]Vítor JM, Vale FF: Alternative therapies for Helicobacter pylori: probiotics and phytomedicine. FEMS Immunol Med Microbiol 2011, 63:153-164.
• [39]Canducci F, Armuzzi A, Cremonini F, Cammarota G, Bartolozzi F, Pola P, Gasbarrini G, Gasbarrini A: A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates. Aliment Pharmacol Ther 2000, 14:1625-1629.
• [40]Szajewska H, Horvath A, Piwowarczyk A: Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment. Aliment Pharmacol Ther 2010, 32:1069-1079.
• [41]Zou J, Dong J, Yu X: Meta-analysis: Lactobacillus containing quadruple therapy versus standard triple first-line therapy for Helicobacter pylori eradication. Helicobacter 2009, 14:97-107.
• [42]Scaccianoce G, Zullo A, Hassan C, Gentili F, Cristofari F, Cardinale V, Gigliotti F, Piglionica D, Morini S: Triple therapies plus different probiotics for Helicobacter pylori eradication. Eur Rev Med Pharmacol Sci 2008, 12:251-256.
• [43]Wang ZH, Gao QY, Fang JY: Meta-Analysis of the Efficacy and Safety of Lactobacillus-containing and Bifidobacterium-containing Probiotic Compound Preparation in Helicobacter pylori Eradication Therapy. J Clin Gastroenterol 2013, 47:25-32.
• [44]Ojetti V, Bruno G, Ainora ME, Gigante G, Rizzo G, Roccarina D, Gasbarrini A: Impact of Lactobacillus reuteri Supplementation on Anti-Helicobacter pylori Levofloxacin-Based Second-Line Therapy. Gastroenterol Res Pract 2012, 2012:740381.
• [45]Du YQ, Su T, Fan JG, Lu YX, Zheng P, Li XH, Guo CY, Xu P, Gong YF, Li ZS: Adjuvant probiotics improve the eradication effect of triple therapy for Helicobacter pylori infection. World J Gastroenterol 2012, 18:6302-6307.
• [46]Manfredi M, Bizzarri B, Sacchero RI, Maccari S, Calabrese L, Fabbian F, De'Angelis GL: Helicobacter pylori infection in clinical practice: probiotics and a combination of probiotics + lactoferrin improve compliance, but not eradication, in sequential therapy. Helicobacter 2012, 17:254-263.
• [47]Tolone S, Pellino V, Vitaliti G, Lanzafame A, Tolone C: Evaluation of Helicobacter Pylori eradication in pediatric patients by triple therapy plus lactoferrin and probiotics compared to triple therapy alone. Ital J Pediatr 2012, 38:63. BioMed Central Full Text
• [48]Cats A, Kuipers EJ, Bosschaert MA, Pot RG, Vandenbroucke-Grauls CM, Kusters JG: Effect of frequent consumption of a Lactobacillus casei-containing milk drink in Helicobacter pylori-colonized subjects. Aliment Pharmacol Ther 2003, 17:429-435.
• [49]Yoon H, Kim N, Kim JY, Park SY, Park JH, Jung HC, Song IS: Effects of multistrain probiotic-containing yogurt on second-line triple therapy for Helicobacter pylori infection. J Gastroenterol Hepatol 2011, 26:44-48.
• [50]Kindermann A, Lopes AI: Helicobacter pylori infection in pediatrics. Helicobacter 2009, 14(Suppl 1):52-57.
• [51]Medeiros JA, Goncalves TM, Boyanova L, Pereira MI, de Carvalho JN, Pereira AM, Cabrita AM: Evaluation of Helicobacter pylori eradication by triple therapy plus Lactobacillus acidophilus compared to triple therapy alone. Eur J Clin Microbiol Infect Dis 2011, 30:555-559.