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Su1688 Helicobacter pylori First-Line Treatment With Clarithromycin and Metronidazole in Patients Allergic to Penicillin: Is it an Acceptable Option?
AGA Abstracts
inverse variance method. RESULTS: The pooled eradication rates by year from Spanish studies evaluating the efficacy of the standard triple regimen revealed a relatively constant rate over the years. Overall, the analysis of the 32 studies (4,727 patients) showed a mean H. pylori cure rate of 80% (95%CI=77-82%) by intention-to-treat and 83% (81-86%) by per-protocol. When only peptic ulcer disease or 7-day regimens were considered, results were similar. Based on 13 studies (3,293 patients), mean clarithromycin resistance rate was 8% (5-10%). CONCLUSION: Although a decrease in the H. pylori eradication rate after triple therapy has been suggested in recent years, cure rates with this regimen did not change in Spain between 1997 and 2008. However, this by no means indicates that the efficacy of standard triple therapy in Spain is acceptable, as it has been calculated to be around only 80%. Therefore, it is evident that new strategies to improve first-line treatment are urgently needed.
population. Methods: MEDLINE and congress abstract searches were performed to identify studies evaluating H. pylori infection prevalence in the Spanish general population. A subanalysis was performed considering only the data from young adults (20-30 years of age). Data was meta-analyzed using the inverse generic variance method. Results: Nineteen studies were included (7,668 individuals). Two studies included only children while 8 studies included both children and adult populations. Reports were published between 1989 and 2007. The mean infection prevalence combining all studies was 48% (95%CI=40-57%). Data were highly heterogeneous (I2=98%), reporting prevalences ranging from 16% to 78%. No time-dependant descending prevalence was demonstrated. In fact, the two most recent studies, from 2006 and 2007, reported prevalences of 69% and 60% respectively. Data from studies including only adults (9 studies) showed highly heterogeneous results (I2=96%), with a mean prevalence of 53% (95%CI=43-63%). The prevalence in young adults (649 individuals' data extracted from the studies) was lower but still a considerably high figure (40%, 95%CI=33-47%); I2=75%). Conclusion: Prevalence of H. pylori infection in Spain is considerably high, approximately 50%. Contrary to what has been reported in other countries, the frequency of infection does not show a descending tendency over time. Even nowadays, the prevalence in young adults (20-30 year old) is still high (40%). Therefore, we can assume that the diseases related to this infection such as peptic ulcer and gastric cancer will continue to be very prevalent over the next few decades.
Su1687 Fourth-Line Rescue Therapy With Rifabutin in Patients With Three H. pylori Eradication Failures Javier P. Gisbert, Manuel Castro-Fernandez, Angeles Perez Aisa, Angel Cosme, Javier Molina-Infante, Luis Rodrigo, Ines Modolell, Jose Luis Cabriada, JoseLuis Gisbert, Eloisa Lamas, Santiago Marcos, Xavier Calvet
Su1690
BACKGROUND: In some cases, Helicobater pylori infection persists even after 3 eradication treatments. AIM: To evaluate the efficacy of an empirical forth-line rescue regimen with rifabutin in patients with 3 eradication failures, extending the experience of an ongoing multicenter study. METHODS: Design: Multicenter, prospective study. Patients: Patients in whom the following 3 eradication treatments had consecutively failed: 1st treatment: PPI + clarithromycin + amoxicillin; 2nd treatment: quadruple therapy (PPI + bismuth + tetracycline + metronidazole); 3rd treatment: PPI + amoxicillin + levofloxacin. Intervention: In patients failing these 3 regimens, a 4th regimen with rifabutin (150 mg b.i.d.), amoxicillin (1 g b.i.d.) and a PPI (standard dose b.i.d.) was prescribed for 10 days. Outcome: Eradication was confirmed using the 13C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: One-hundred patients (mean age 50 years, 39% males, 31% peptic ulcer/69% functional dyspepsia) were included. Compliance: 8 patients did not take correctly the medication (in 6 cases due to adverse effects). Per-protocol and intention-to-treat eradication rates were 52% (95%CI=41-63%) and 50% (40-60%). Adverse effects were reported in 30 (30%) patients: nausea/vomiting (13 patients), asthenia/anorexia (8), abdominal pain (7), diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia (2), leucopoenia (<1,500 neutrophils) (2), thrombopoenia (<150,000 platelets) (2), headache (1), and aphthous stomatitis (1). Myelotoxicity resolved spontaneously in all cases. CONCLUSION: Even after 3 previous H. pylori eradication failures, an empirical fourth-line rescue treatment with rifabutin may be effective in approximately 50% of the cases. Therefore, rifabutin-based rescue therapy constitutes a valid strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin
Second-Line Rescue Triple Therapy With Levofloxacin After Failure of Quadruple Non-Bismuth “Sequential” or “Concomitant” Treatment Javier P. Gisbert, Alicia C Marin, Javier Molina-Infante BACKGROUND: Quadruple non-bismuth containing “sequential” and “concomitant” regimens, including a PPI, amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for Helicobacter pylori infection. Eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles. AIM: To evaluate the efficacy and tolerability of a second-line levofloxacin-containing triple regimen (PPI-amoxicillin-levofloxacin) in the eradication of H. pylori after quadruple nonbismuth containing treatment failure. METHODS: Design: Prospective multicenter study. Patients: In whom a quadruple non-bismuth containing regimen, administered either sequentially (PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for 5 more days) or concomitantly (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed. Intervention: levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI (standard dose b.i.d.) for 10 days. Outcome: Eradication was confirmed with 13Curea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: Up to now, 63 consecutive patients have been included (mean age 50 years, 40% males, 21% smokers, 17% peptic ulcer and 83% dyspepsia): 21 after “sequential”, and 42 after “concomitant” treatment failure. All patients took all medications correctly. Overall, per-protocol and intention-to-treat H. pylori eradication rates were both 78% (95%CI=67-85%). Respective cure rates for “sequential” and “concomitant” failure regimens were 76% (16/21) and 79% (33/42). Adverse effects were reported in four (6%) patients: metallic taste and heartburn, diarrhea, vaginal candidiasis, and asthenia; all of them were mild. CONCLUSION: Tenday levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous quadruple non-bismuth “sequential” or “concomitant” treatment failure.
Su1688 Helicobacter pylori First-Line Treatment With Clarithromycin and Metronidazole in Patients Allergic to Penicillin: Is it an Acceptable Option? Javier P. Gisbert, Angeles Perez Aisa, Manuel Castro-Fernandez, Jesus Barrio, Luis Rodrigo, Angel Cosme, JoseLuis Gisbert, Santiago Marcos
Su1691
BACKGROUND: In patients allergic to penicillin, which constitutes a relatively common subgroup, a triple therapy including a proton pump inhibitor (PPI), clarithromycin, and a nitroimidazole represents one of the most frequently recommended regimens for the treatment of Helicobacter pylori infection. However, this regimen may be relatively ineffective in areas of high clarithromycin resistance, where a bismuth-containing quadruple therapy may be preferred. AIM: To assess the efficacy and safety of H. pylori first-line treatment with a PPI, clarithromycin and metronidazole in patients allergic to penicillin, extending the experience of an ongoing multicenter study. METHODS: Design: Prospective multicenter study including consecutive patients allergic to penicillin. Intervention: PPI (standard dose), clarithromycin (500 mg b.i.d.), and metronidazole (500 mg b.i.d.) for 7 days. Outcome: Eradication was confirmed using the 13C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: 114 patients allergic to penicillin were included (mean age 52 years, 40% males, 44% peptic ulcer, 56% functional dyspepsia). Compliance: 7 patients (6%) did not take the medication correctly (due to adverse effects in 2 cases). Per-protocol and intention-to-treat eradication rates were 59% (95%CI=49-68%) and 56% (47-66%). Adverse effects were reported in 15 patients (13%): metallic taste (7 patients), nausea (8 patients), vomiting (1 patient), and abdominal pain (3 patients). CONCLUSION: Allergic to penicillin H. pylori infected patients may be treated with a first-line treatment combining a PPI, clarithromycin and metronidazole, but its efficacy is clearly disappointing. Bismuth-containing quadruple therapy (that is, PPI, bismuth, tetracycline and metronidazole) may be a better option in areas of high clarithromycin resistance, but this will need to be confirmed in future studies.
Moxifloxacin Containing Triple Therapy vs. Moxifloxacin and BismuthContaining Quadruple Therapy for First-Line Treatment of Helicobacter pylori (H. pylori) Infection Antonio Francesco Ciccaglione, Luigina Cellini, Laurino Grossi, Ada Maria Di tullio, Mauro Pagliaro, Roberta Tavani, Sila Cocciolillo, Leonardo Marzio BACKGROUND: Moxifloxacin (MOXI) based triple therapy has been suggested as an alternative first-line therapy for H. pylori infection in geographical areas with clarithromycin resistance exceeds 30% of strains. The resistance rate of H. pylori to MOXI is increased in the last two years from 12% to 25% in patients never treated in our region, while resistance to clarithromycin is stable, ranging from 40% to 59 % (unpublished results). In a recent trial, it has been shown that the addition of bismuth subcitrate to the standard first line therapy improves eradication rate despite antibiotic resistance (Lancet 2011;377: 905-913). AIM: To compare triple therapy with pantoprazole 20 mg b.i.d., amoxicillin 1 g b.i.d and MOXI 400 mg b.i.d. for 10 days (PAM) vs quadruple therapy with pantoprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., MOXI 400 mg b.i.d. and bismuth subcitrate 240 mg b.i.d. for 10 days (PAMB) for the first-line treatment of H. pylori infection. METHODS: Consecutive H. pylori positive patients never treated in their past for the infection were randomly treated with PAM or PAMB for 10 days. All patients were found positive at 13 C-Urea breath test (UBT) performed within ten days prior to the start of the study . Successful outcome was confirmed with an UBT performed 8 weeks after the end of treatment with a DOB value less of 5. Chi square analysis was used for statistical comparison. RESULTS: 57 patients were enrolled in the PAM group and 50 in the PAMB group. One patient in each group did not return to control. H. pylori eradication rate was statistically significantly higher in the PAMB group vs the PAM group either with the per protocol (PP) and intention to treat (ITT) analysis ( PP: PAMB 93.8 % (46/49), PAM 78.5 (44/56) P<0.02; ITT: PAMB 92 % (46/50), PAM 77.1 % (44/57), P<0.03). Both treatment were well tolerated with no reported side effects. CONCLUSION: the eradication rate of MOXI containing triple regimen may be improved with the addition of bismuth subcitrate that therefore may be considered as a valuable adjuvant to triple therapy in those areas where H. pylori shows an high resistance to fluorquinolones.
Su1689 Helicobacter pylori Infection in Spain: Is Its Prevalence Really Decreasing? Javier P. Gisbert, Adrian G. McNicholl Background: Knowing the Helicobacter pylori prevalence in the general population is important in order to estimate the population's risk to develop diseases related with this infection such as peptic ulcer and gastric cancer. It has been suggested that H. pylori's prevalence is decreasing over time in developed countries and therefore the infection's frequency in young adults is significantly lower than that of the general population. Aim: To review the studies evaluating H. pylori prevalence in both the Spanish general population and its young adult
AGA Abstracts
S-482
inverse variance method. RESULTS: The pooled eradication rates by year from Spanish studies evaluating the efficacy of the standard triple regimen revealed a relatively constant rate over the years. Overall, the analysis of the 32 studies (4,727 patients) showed a mean H. pylori cure rate of 80% (95%CI=77-82%) by intention-to-treat and 83% (81-86%) by per-protocol. When only peptic ulcer disease or 7-day regimens were considered, results were similar. Based on 13 studies (3,293 patients), mean clarithromycin resistance rate was 8% (5-10%). CONCLUSION: Although a decrease in the H. pylori eradication rate after triple therapy has been suggested in recent years, cure rates with this regimen did not change in Spain between 1997 and 2008. However, this by no means indicates that the efficacy of standard triple therapy in Spain is acceptable, as it has been calculated to be around only 80%. Therefore, it is evident that new strategies to improve first-line treatment are urgently needed.
population. Methods: MEDLINE and congress abstract searches were performed to identify studies evaluating H. pylori infection prevalence in the Spanish general population. A subanalysis was performed considering only the data from young adults (20-30 years of age). Data was meta-analyzed using the inverse generic variance method. Results: Nineteen studies were included (7,668 individuals). Two studies included only children while 8 studies included both children and adult populations. Reports were published between 1989 and 2007. The mean infection prevalence combining all studies was 48% (95%CI=40-57%). Data were highly heterogeneous (I2=98%), reporting prevalences ranging from 16% to 78%. No time-dependant descending prevalence was demonstrated. In fact, the two most recent studies, from 2006 and 2007, reported prevalences of 69% and 60% respectively. Data from studies including only adults (9 studies) showed highly heterogeneous results (I2=96%), with a mean prevalence of 53% (95%CI=43-63%). The prevalence in young adults (649 individuals' data extracted from the studies) was lower but still a considerably high figure (40%, 95%CI=33-47%); I2=75%). Conclusion: Prevalence of H. pylori infection in Spain is considerably high, approximately 50%. Contrary to what has been reported in other countries, the frequency of infection does not show a descending tendency over time. Even nowadays, the prevalence in young adults (20-30 year old) is still high (40%). Therefore, we can assume that the diseases related to this infection such as peptic ulcer and gastric cancer will continue to be very prevalent over the next few decades.
Su1687 Fourth-Line Rescue Therapy With Rifabutin in Patients With Three H. pylori Eradication Failures Javier P. Gisbert, Manuel Castro-Fernandez, Angeles Perez Aisa, Angel Cosme, Javier Molina-Infante, Luis Rodrigo, Ines Modolell, Jose Luis Cabriada, JoseLuis Gisbert, Eloisa Lamas, Santiago Marcos, Xavier Calvet
Su1690
BACKGROUND: In some cases, Helicobater pylori infection persists even after 3 eradication treatments. AIM: To evaluate the efficacy of an empirical forth-line rescue regimen with rifabutin in patients with 3 eradication failures, extending the experience of an ongoing multicenter study. METHODS: Design: Multicenter, prospective study. Patients: Patients in whom the following 3 eradication treatments had consecutively failed: 1st treatment: PPI + clarithromycin + amoxicillin; 2nd treatment: quadruple therapy (PPI + bismuth + tetracycline + metronidazole); 3rd treatment: PPI + amoxicillin + levofloxacin. Intervention: In patients failing these 3 regimens, a 4th regimen with rifabutin (150 mg b.i.d.), amoxicillin (1 g b.i.d.) and a PPI (standard dose b.i.d.) was prescribed for 10 days. Outcome: Eradication was confirmed using the 13C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: One-hundred patients (mean age 50 years, 39% males, 31% peptic ulcer/69% functional dyspepsia) were included. Compliance: 8 patients did not take correctly the medication (in 6 cases due to adverse effects). Per-protocol and intention-to-treat eradication rates were 52% (95%CI=41-63%) and 50% (40-60%). Adverse effects were reported in 30 (30%) patients: nausea/vomiting (13 patients), asthenia/anorexia (8), abdominal pain (7), diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia (2), leucopoenia (<1,500 neutrophils) (2), thrombopoenia (<150,000 platelets) (2), headache (1), and aphthous stomatitis (1). Myelotoxicity resolved spontaneously in all cases. CONCLUSION: Even after 3 previous H. pylori eradication failures, an empirical fourth-line rescue treatment with rifabutin may be effective in approximately 50% of the cases. Therefore, rifabutin-based rescue therapy constitutes a valid strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin
Second-Line Rescue Triple Therapy With Levofloxacin After Failure of Quadruple Non-Bismuth “Sequential” or “Concomitant” Treatment Javier P. Gisbert, Alicia C Marin, Javier Molina-Infante BACKGROUND: Quadruple non-bismuth containing “sequential” and “concomitant” regimens, including a PPI, amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for Helicobacter pylori infection. Eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles. AIM: To evaluate the efficacy and tolerability of a second-line levofloxacin-containing triple regimen (PPI-amoxicillin-levofloxacin) in the eradication of H. pylori after quadruple nonbismuth containing treatment failure. METHODS: Design: Prospective multicenter study. Patients: In whom a quadruple non-bismuth containing regimen, administered either sequentially (PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for 5 more days) or concomitantly (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed. Intervention: levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI (standard dose b.i.d.) for 10 days. Outcome: Eradication was confirmed with 13Curea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: Up to now, 63 consecutive patients have been included (mean age 50 years, 40% males, 21% smokers, 17% peptic ulcer and 83% dyspepsia): 21 after “sequential”, and 42 after “concomitant” treatment failure. All patients took all medications correctly. Overall, per-protocol and intention-to-treat H. pylori eradication rates were both 78% (95%CI=67-85%). Respective cure rates for “sequential” and “concomitant” failure regimens were 76% (16/21) and 79% (33/42). Adverse effects were reported in four (6%) patients: metallic taste and heartburn, diarrhea, vaginal candidiasis, and asthenia; all of them were mild. CONCLUSION: Tenday levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous quadruple non-bismuth “sequential” or “concomitant” treatment failure.
Su1688 Helicobacter pylori First-Line Treatment With Clarithromycin and Metronidazole in Patients Allergic to Penicillin: Is it an Acceptable Option? Javier P. Gisbert, Angeles Perez Aisa, Manuel Castro-Fernandez, Jesus Barrio, Luis Rodrigo, Angel Cosme, JoseLuis Gisbert, Santiago Marcos
Su1691
BACKGROUND: In patients allergic to penicillin, which constitutes a relatively common subgroup, a triple therapy including a proton pump inhibitor (PPI), clarithromycin, and a nitroimidazole represents one of the most frequently recommended regimens for the treatment of Helicobacter pylori infection. However, this regimen may be relatively ineffective in areas of high clarithromycin resistance, where a bismuth-containing quadruple therapy may be preferred. AIM: To assess the efficacy and safety of H. pylori first-line treatment with a PPI, clarithromycin and metronidazole in patients allergic to penicillin, extending the experience of an ongoing multicenter study. METHODS: Design: Prospective multicenter study including consecutive patients allergic to penicillin. Intervention: PPI (standard dose), clarithromycin (500 mg b.i.d.), and metronidazole (500 mg b.i.d.) for 7 days. Outcome: Eradication was confirmed using the 13C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: 114 patients allergic to penicillin were included (mean age 52 years, 40% males, 44% peptic ulcer, 56% functional dyspepsia). Compliance: 7 patients (6%) did not take the medication correctly (due to adverse effects in 2 cases). Per-protocol and intention-to-treat eradication rates were 59% (95%CI=49-68%) and 56% (47-66%). Adverse effects were reported in 15 patients (13%): metallic taste (7 patients), nausea (8 patients), vomiting (1 patient), and abdominal pain (3 patients). CONCLUSION: Allergic to penicillin H. pylori infected patients may be treated with a first-line treatment combining a PPI, clarithromycin and metronidazole, but its efficacy is clearly disappointing. Bismuth-containing quadruple therapy (that is, PPI, bismuth, tetracycline and metronidazole) may be a better option in areas of high clarithromycin resistance, but this will need to be confirmed in future studies.
Moxifloxacin Containing Triple Therapy vs. Moxifloxacin and BismuthContaining Quadruple Therapy for First-Line Treatment of Helicobacter pylori (H. pylori) Infection Antonio Francesco Ciccaglione, Luigina Cellini, Laurino Grossi, Ada Maria Di tullio, Mauro Pagliaro, Roberta Tavani, Sila Cocciolillo, Leonardo Marzio BACKGROUND: Moxifloxacin (MOXI) based triple therapy has been suggested as an alternative first-line therapy for H. pylori infection in geographical areas with clarithromycin resistance exceeds 30% of strains. The resistance rate of H. pylori to MOXI is increased in the last two years from 12% to 25% in patients never treated in our region, while resistance to clarithromycin is stable, ranging from 40% to 59 % (unpublished results). In a recent trial, it has been shown that the addition of bismuth subcitrate to the standard first line therapy improves eradication rate despite antibiotic resistance (Lancet 2011;377: 905-913). AIM: To compare triple therapy with pantoprazole 20 mg b.i.d., amoxicillin 1 g b.i.d and MOXI 400 mg b.i.d. for 10 days (PAM) vs quadruple therapy with pantoprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., MOXI 400 mg b.i.d. and bismuth subcitrate 240 mg b.i.d. for 10 days (PAMB) for the first-line treatment of H. pylori infection. METHODS: Consecutive H. pylori positive patients never treated in their past for the infection were randomly treated with PAM or PAMB for 10 days. All patients were found positive at 13 C-Urea breath test (UBT) performed within ten days prior to the start of the study . Successful outcome was confirmed with an UBT performed 8 weeks after the end of treatment with a DOB value less of 5. Chi square analysis was used for statistical comparison. RESULTS: 57 patients were enrolled in the PAM group and 50 in the PAMB group. One patient in each group did not return to control. H. pylori eradication rate was statistically significantly higher in the PAMB group vs the PAM group either with the per protocol (PP) and intention to treat (ITT) analysis ( PP: PAMB 93.8 % (46/49), PAM 78.5 (44/56) P<0.02; ITT: PAMB 92 % (46/50), PAM 77.1 % (44/57), P<0.03). Both treatment were well tolerated with no reported side effects. CONCLUSION: the eradication rate of MOXI containing triple regimen may be improved with the addition of bismuth subcitrate that therefore may be considered as a valuable adjuvant to triple therapy in those areas where H. pylori shows an high resistance to fluorquinolones.
Su1689 Helicobacter pylori Infection in Spain: Is Its Prevalence Really Decreasing? Javier P. Gisbert, Adrian G. McNicholl Background: Knowing the Helicobacter pylori prevalence in the general population is important in order to estimate the population's risk to develop diseases related with this infection such as peptic ulcer and gastric cancer. It has been suggested that H. pylori's prevalence is decreasing over time in developed countries and therefore the infection's frequency in young adults is significantly lower than that of the general population. Aim: To review the studies evaluating H. pylori prevalence in both the Spanish general population and its young adult
AGA Abstracts
S-482