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Sa1919 Evaluation of a Novel Office Based 14C Urea Breath Test, Heliprobe®, in Patients Undergoing Endoscopy
AGA Abstracts
Sa1916
(33%) patients, the most frequent being: nausea/vomiting (severe in 2 patients), asthenia/ anorexia, abdominal pain, diarrhea, fever, metallic taste, myalgia, hypertransaminasemia, leucopoenia (,1,500 neutrophils), thrombopoenia ( ,150,000 platelets), headache, and aphthous stomatitis. 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, rifabutinbased 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 NonBismuth Quadruple "Sequential" or "Concomitant" Treatment to Eradicate H. pylori Infection Javier P. Gisbert, Javier Molina-Infante, Alicia C Marin, Gema Vinagre Rodriguez, Jesus Barrio, Adrian G. McNicholl BACKGROUND: Non-bismuth quadruple "sequential" and "concomitant" regimens, including a PPI, amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as firstline 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 non-bismuth quadruple containing treatment failure. METHODS: Design: Prospective multicenter study. Patients: In whom a non-bismuth quadruple 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 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: 100 consecutive patients were included (mean age 50 years, 62% females, 12% peptic ulcer and 88% dyspepsia): 37 after "sequential", and 63 after "concomitant" treatment failure. All patients took all medications correctly. Overall, perprotocol and intention-to-treat H. pylori eradication rates were 75.5% (95% CI=66-85%) and 74% (65-83%). Respective intention-to-treat cure rates for "sequential" and "concomitant" failure regimens were 74.4% and 71.4%. Adverse effects were reported in six (6%) patients; all of them were mild. CONCLUSION: Ten-day levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous nonbismuth quadruple "sequential" or "concomitant" treatment failure.
Sa1919 Evaluation of a Novel Office Based 14C Urea Breath Test, Heliprobe®, in Patients Undergoing Endoscopy Vivek Kumbhari, Nabil Rahme, Christopher Meredith Background: The prevalence of Helicobacter pylori (HP) infection in the United States varies between 14-70% depending on the method of testing and population studied. As there is a large population at risk, testing should ideally be accurate, non-invasive, accessible and cost effective. The Heliprobe® is a new 14C urea breath test which provides immediate results, is portable and inexpensive. Heliprobe® allows the practitioner to provide an office based test and treat strategy for HP. Aim: Our aim was to determine the accuracy of Heliprobe® in the diagnosis of Helicobacter pylori infection compared to a urease test and histopathology in a mixed ethnic patient population. Methods: 820 consecutive patients with a variety of upper gastrointestinal symptoms were referred to a metropolitan endoscopy center for elective gastroscopy between December 2011 and September 2012. At gastroscopy, biopsies were taken from the antrum and body for urease testing and histopathology. A nurse practitioner performed a Heliprobe® test on each patient according to the manufacturers recommendations. Histopathology alone was used as the gold standard and subsequently the sensitivity, specificity, positive predictive value(PPV) and negative predictive value(NPV) of Heliprobe® and urease test were determined. McNemar's test was used to determine the significance of differences between Heliproibe® and a urease test. Differences were considered significant at p ,0.05. Results: 790 patients (324M, 466F) had all three tests performed. The mean age of the study population was 55yrs and the prevalence of HP was 13% (103/ 790). Heliprobe® had sensitivity 83.5%, specificity 99.6%, PPV 99.6% and NPV 97.6%. Urease test had a sensitivity 80.6%, specificity 99.4%, PPV 95.4%, NPV 97.2%. Heliprobe® had a similar ability for the detection of HP infection compared to a urease test (McNemar's test, p = 0.83). Conclusions: The prevalence of HP was low at 13% in this large cohort. Heliprobe® proved of no additional benefit to a urease test in the diagnosis of HP for patients undergoing an endoscopy.
Sa1917 Third-Line Rescue Therapy With Bismuth-Containing Quadruple Regimen After Failure of Two Treatments (With Clarithromycin and Levofloxacin) to Eradicate Helicobacter pylori Infection Javier P. Gisbert, Angeles Perez Aisa, Luis Rodrigo, Javier Molina-Infante, Ines Modolell, Fernando Bermejo, Manuel Castro-Fernandez, Rosario Anton, Begoña Sacristán, Angel Cosme, Jesus Barrio, Yamal Harb, Martha González-Bárcenas, Miguel Fernandez Bermejo, Alicia Algaba, Alicia C Marin, Adrian G. McNicholl BACKGROUND: Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in a considerable number of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in more than 20% of patients. AIM: To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive H. pylori eradication failures. METHODS: Design: Prospective multicenter study. Patients: In whom a first treatment with PPI-clarithromycin-amoxicillin and a second with PPI-amoxicillin-levofloxacin had failed. Intervention: A third eradication regimen with a PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.) was prescribed for 7-14 days. Outcome: Eradication was confirmed using the 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: Two-hundred patients (mean age 50 years, 55% females, 20% with peptic ulcer disease and 80% with uninvestigated/ functional dyspepsia) were initially included, and 2 were lost to follow-up. 97% of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67% (95% confidence interval, 60-74%) and 65% (58-72%). Adverse effects were reported in 22% of the patients, the most common being nausea (12%), abdominal pain (11%), metallic taste (8.5%) and diarrhea (8%); none of them was severe. CONCLUSION: A bismuthcontaining quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin-containing and levofloxacin-containing triple therapies.
Sa1920 Genomic Structure of Clarithromycin Resistant Helicobacter pylori Using Next Generation Sequencing Akira Iwamoto, Toshihito Tanahashi, Rina Okada, Yukio Yoshida, Kaoru Kikuchi, Yoshihide Keida, Masaru Yoshida, Takeshi Azuma Background & Aims: Proton pump inhibitor and two types of antimicrobial agents, amoxicillin (AMPC), and clarithromycin (CAM), have been widely used in the eradication of Helicobacter pylori (H. pylori). However, antibiotic resistant strain has been rapidly increased as an important factor for the failure of eradication. Previously, special attention was given to the mechanism of CAM resistance, and mutations of A2143G or A2144G in the bacterial 23S rRNA gene were well established with the relation of CAM resistance. Nevertheless, it remains largely unclear about the other mutations or aberrant genomic structure in CAM resistance. Recent advances of next-generation sequencing (NGS) can read DNA sequences less time and lower cost than classical Sanger sequence and offer the comprehensive and broad view of genomic structure in micro-organism. In this study, we first defined the complete genomic structure of CAM resistant H. pylori and analyzed the bacterial genome with the novel mutations of CAM resistance. Methods & Results: Allele specific primer PCR (ASP-PCR) to 23S rRNA gene Eighty-one H. pylori were isolated from Japanese patients of chronic gastritis and surveyed with ASP-PCR method. This method could be effectively applied in detecting the A2143G or A2144G in 23S rRNA gene and determine whether H. pylori is wild or resistant strain to CAM. As a result, 22 clinical strains (27.1% = 22/ 81) indicated the presence of these mutations. Whole genome sequencing Whole-genome sequencing of ATCC26695 and J99 were conducted with MiSeq system (Illumina) and compared with the original sequences deposited in GenBank. Total consensus coverage (TCC) of reference strains were 99.98% and 99.93%, and average coverage (AC) were over 40. Furthermore, whole-genome sequencing of two CAM resistant and 10 wild-type clinical strains were determined. TCCs were nearly 90% mapped to the reference sequence of ATCC26695, and ACs were over 40, indicating good quality data. In two CAM resistant strains, A2144G mutation was found in all sequence reads ( . 100) at that position. In contrast, there was no mutation at those positions in 10 wild-type strains in agreement with the results of ASP-PCR. Comparative analysis of the genomic sequences in CAM resistant and wild-type strains revealed several mutations in H. pylori genome. Now, we increase the number of analyzed samples. Summary: In addition to the A2143G or A2144G mutations, we found the other mutations and genomic structure that underlie the CAM resistance in H. pylori. NGS is an effective tool to detect a novel mutation and aberrant genomic structures related with antibiotic resistance.
Sa1918 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 ABSTRACT BODY: 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 and twenty-one patients (mean age 50 years, 41% males, 27% peptic ulcer/ 73% 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 54% (95%CI=44-64%) and 52% (43-61%). Adverse effects were reported in 40
AGA Abstracts
S-334
Sa1916
(33%) patients, the most frequent being: nausea/vomiting (severe in 2 patients), asthenia/ anorexia, abdominal pain, diarrhea, fever, metallic taste, myalgia, hypertransaminasemia, leucopoenia (,1,500 neutrophils), thrombopoenia ( ,150,000 platelets), headache, and aphthous stomatitis. 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, rifabutinbased 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 NonBismuth Quadruple "Sequential" or "Concomitant" Treatment to Eradicate H. pylori Infection Javier P. Gisbert, Javier Molina-Infante, Alicia C Marin, Gema Vinagre Rodriguez, Jesus Barrio, Adrian G. McNicholl BACKGROUND: Non-bismuth quadruple "sequential" and "concomitant" regimens, including a PPI, amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as firstline 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 non-bismuth quadruple containing treatment failure. METHODS: Design: Prospective multicenter study. Patients: In whom a non-bismuth quadruple 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 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: 100 consecutive patients were included (mean age 50 years, 62% females, 12% peptic ulcer and 88% dyspepsia): 37 after "sequential", and 63 after "concomitant" treatment failure. All patients took all medications correctly. Overall, perprotocol and intention-to-treat H. pylori eradication rates were 75.5% (95% CI=66-85%) and 74% (65-83%). Respective intention-to-treat cure rates for "sequential" and "concomitant" failure regimens were 74.4% and 71.4%. Adverse effects were reported in six (6%) patients; all of them were mild. CONCLUSION: Ten-day levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous nonbismuth quadruple "sequential" or "concomitant" treatment failure.
Sa1919 Evaluation of a Novel Office Based 14C Urea Breath Test, Heliprobe®, in Patients Undergoing Endoscopy Vivek Kumbhari, Nabil Rahme, Christopher Meredith Background: The prevalence of Helicobacter pylori (HP) infection in the United States varies between 14-70% depending on the method of testing and population studied. As there is a large population at risk, testing should ideally be accurate, non-invasive, accessible and cost effective. The Heliprobe® is a new 14C urea breath test which provides immediate results, is portable and inexpensive. Heliprobe® allows the practitioner to provide an office based test and treat strategy for HP. Aim: Our aim was to determine the accuracy of Heliprobe® in the diagnosis of Helicobacter pylori infection compared to a urease test and histopathology in a mixed ethnic patient population. Methods: 820 consecutive patients with a variety of upper gastrointestinal symptoms were referred to a metropolitan endoscopy center for elective gastroscopy between December 2011 and September 2012. At gastroscopy, biopsies were taken from the antrum and body for urease testing and histopathology. A nurse practitioner performed a Heliprobe® test on each patient according to the manufacturers recommendations. Histopathology alone was used as the gold standard and subsequently the sensitivity, specificity, positive predictive value(PPV) and negative predictive value(NPV) of Heliprobe® and urease test were determined. McNemar's test was used to determine the significance of differences between Heliproibe® and a urease test. Differences were considered significant at p ,0.05. Results: 790 patients (324M, 466F) had all three tests performed. The mean age of the study population was 55yrs and the prevalence of HP was 13% (103/ 790). Heliprobe® had sensitivity 83.5%, specificity 99.6%, PPV 99.6% and NPV 97.6%. Urease test had a sensitivity 80.6%, specificity 99.4%, PPV 95.4%, NPV 97.2%. Heliprobe® had a similar ability for the detection of HP infection compared to a urease test (McNemar's test, p = 0.83). Conclusions: The prevalence of HP was low at 13% in this large cohort. Heliprobe® proved of no additional benefit to a urease test in the diagnosis of HP for patients undergoing an endoscopy.
Sa1917 Third-Line Rescue Therapy With Bismuth-Containing Quadruple Regimen After Failure of Two Treatments (With Clarithromycin and Levofloxacin) to Eradicate Helicobacter pylori Infection Javier P. Gisbert, Angeles Perez Aisa, Luis Rodrigo, Javier Molina-Infante, Ines Modolell, Fernando Bermejo, Manuel Castro-Fernandez, Rosario Anton, Begoña Sacristán, Angel Cosme, Jesus Barrio, Yamal Harb, Martha González-Bárcenas, Miguel Fernandez Bermejo, Alicia Algaba, Alicia C Marin, Adrian G. McNicholl BACKGROUND: Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in a considerable number of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in more than 20% of patients. AIM: To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive H. pylori eradication failures. METHODS: Design: Prospective multicenter study. Patients: In whom a first treatment with PPI-clarithromycin-amoxicillin and a second with PPI-amoxicillin-levofloxacin had failed. Intervention: A third eradication regimen with a PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.) was prescribed for 7-14 days. Outcome: Eradication was confirmed using the 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: Two-hundred patients (mean age 50 years, 55% females, 20% with peptic ulcer disease and 80% with uninvestigated/ functional dyspepsia) were initially included, and 2 were lost to follow-up. 97% of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67% (95% confidence interval, 60-74%) and 65% (58-72%). Adverse effects were reported in 22% of the patients, the most common being nausea (12%), abdominal pain (11%), metallic taste (8.5%) and diarrhea (8%); none of them was severe. CONCLUSION: A bismuthcontaining quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin-containing and levofloxacin-containing triple therapies.
Sa1920 Genomic Structure of Clarithromycin Resistant Helicobacter pylori Using Next Generation Sequencing Akira Iwamoto, Toshihito Tanahashi, Rina Okada, Yukio Yoshida, Kaoru Kikuchi, Yoshihide Keida, Masaru Yoshida, Takeshi Azuma Background & Aims: Proton pump inhibitor and two types of antimicrobial agents, amoxicillin (AMPC), and clarithromycin (CAM), have been widely used in the eradication of Helicobacter pylori (H. pylori). However, antibiotic resistant strain has been rapidly increased as an important factor for the failure of eradication. Previously, special attention was given to the mechanism of CAM resistance, and mutations of A2143G or A2144G in the bacterial 23S rRNA gene were well established with the relation of CAM resistance. Nevertheless, it remains largely unclear about the other mutations or aberrant genomic structure in CAM resistance. Recent advances of next-generation sequencing (NGS) can read DNA sequences less time and lower cost than classical Sanger sequence and offer the comprehensive and broad view of genomic structure in micro-organism. In this study, we first defined the complete genomic structure of CAM resistant H. pylori and analyzed the bacterial genome with the novel mutations of CAM resistance. Methods & Results: Allele specific primer PCR (ASP-PCR) to 23S rRNA gene Eighty-one H. pylori were isolated from Japanese patients of chronic gastritis and surveyed with ASP-PCR method. This method could be effectively applied in detecting the A2143G or A2144G in 23S rRNA gene and determine whether H. pylori is wild or resistant strain to CAM. As a result, 22 clinical strains (27.1% = 22/ 81) indicated the presence of these mutations. Whole genome sequencing Whole-genome sequencing of ATCC26695 and J99 were conducted with MiSeq system (Illumina) and compared with the original sequences deposited in GenBank. Total consensus coverage (TCC) of reference strains were 99.98% and 99.93%, and average coverage (AC) were over 40. Furthermore, whole-genome sequencing of two CAM resistant and 10 wild-type clinical strains were determined. TCCs were nearly 90% mapped to the reference sequence of ATCC26695, and ACs were over 40, indicating good quality data. In two CAM resistant strains, A2144G mutation was found in all sequence reads ( . 100) at that position. In contrast, there was no mutation at those positions in 10 wild-type strains in agreement with the results of ASP-PCR. Comparative analysis of the genomic sequences in CAM resistant and wild-type strains revealed several mutations in H. pylori genome. Now, we increase the number of analyzed samples. Summary: In addition to the A2143G or A2144G mutations, we found the other mutations and genomic structure that underlie the CAM resistance in H. pylori. NGS is an effective tool to detect a novel mutation and aberrant genomic structures related with antibiotic resistance.
Sa1918 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 ABSTRACT BODY: 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 and twenty-one patients (mean age 50 years, 41% males, 27% peptic ulcer/ 73% 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 54% (95%CI=44-64%) and 52% (43-61%). Adverse effects were reported in 40
AGA Abstracts
S-334