- Email: [email protected]
Assessment of Helicobacter pylori infection in primary care: Which test to use?
method for H. pylori isolat=onfrom saliva and other nonsterile--site specimens. METHODS: H. pyloriwas inoculated =nto normal saline or saliva and incubated in various concentrations of urea and HCI at 4, 22 or 3TC for 5 minutes, then plated onto nonselective media. Survival rates of the H. pylori type stra=n and fresh clinical isolates were then compared. RESULTS: H. pylori survived a briet exposure to HCI as high as 0.48 N (pH 0.36) in the presence of 1 M urea. Optimal H, pylori recoveries with minimal growth of background microflora were obtained with concentrations of 0.06 N to 0.24 N HCI (pH 1.2 - 0.65 ) plus 20to 1000 mM urea at 37 °C. After exposure to the optimal mixture of urea-HCI, 13 clinical strains gave survival rates ranging from 14% to 90% of the initial inoculum (median 43%), compared to the ATCCtype strain which had a survival rate of 5-8% of initial inoculum. When saliva spiked with H. py/oriwas incubated in the optimal mixture of urea-HCI,background microorganisms in saliva were almost completely inhibited. Using this approach, we were abte to isolate H. py/od even at low inocula of H. py/oriin saliva (100 CFU/ml), and from highly contaminated gastric biopsy or H. py/ori culture specimens for which conventional selective enrichment media had not been successful. CONCLUSIONS:We have developed a reproducible, novel method for H. py/or/isolation from contaminated samples. This novel method may be useful for the isolation of H. pylodfrom nonsterile-site clinical specimens and from environmental specimens and thereby facilitate the identification of environmental reservoirs of H. pylori.
not treat based on a positive result. Most use appropriate combination regimens although knowledge of antibiotic resistance is suboptimal.
2945
Hellcobacter pylori (Hp) Infection Plays a Crucial Role in the Majority of Alropbi¢ Body Gastritis (ABG) Patients Bruno Annibale, Edith Lahner, Cristina Grossi, Univ La Sapienza, Rome Italy; Riccardo Negrini, Spedali Civili, Brescia Italy; Pietro Caruana, Cesare Bordi, Univ, Parma Italy; Gabriele Capurso, Gianfranco Delle Fave, Univ La Sapienza, Rome Italy Background:ABG is characterizedby atrophy of oxyntic mucosa, hypo/achlorbydrla and fasting hypergastrinemia. It is now apparent that Hp may be involved in the induction of ABG. Hp infection may be detected by histology in a small proportion of ABG patients, but it has been recently suggested that in ABG patients the presence of circulating antibodies against Hp could indicate active infection too. Aim:to investigate the prevalence of Hp infection on the basis of histology and serology, in ABG patients. Patients:150 consecutive ABG outpatients (991:/51M, aged 22-83)diagnosed by a screening program performed on subjects with unexplained microcytic (n = 65) or macrocytic (n = 68)anemia or long-standing dyspepsia (n = 19). Methods:All patients had assesssment of monoclonal IgGHp and PC antibodies, fasting gastrin levels and gastroscopy with antrai (n = 3) and corporal (n = 3) biopsies. Gastritis was e s s e ~ according to the updated Sydney System. Results:24.6% of patients were Hp negative both at histology and serology (Group A), 52.7% were negativeat histology but positive at samlogy(Group B), 22.6% had histology positive for Hp (Group C).IgGHp levels (U/ml)were significantly different among the 3 groups, being the median respectively for groups A,B and C: 180 (0435), 2070 (465-75000) and 16350 (345-75000). There was also a clear gradient for the mean corporal atrophy (Group A> Group B> Group C)which was significantly higher in group A compared to B(2.75_+0.09 vs 2.43_+0.08; p<0.05)and in group B compared to C (1.79_+0.11; p<0.001). Corporal atrophy resulted correlated directly with PC Ab titer (r=0.04791; p<0.05) and inversely with IgGHp (r-0.2322; p<0.0001). Pernicious anemia was observed respectively in 75.6%, 45.6% and 11.8% in Groups A,B and C. Conclusions:This study demonstrates that Hp infection can be detected in 2/3 of ABG patients performing both histological and serological assessment. The observed correlation between the progression of corporal atrophy and both the increase of PC Ab titer and the decrease of IgGHp, strongly suggests that Hp infection is related with the induction of the oxyntic damage.
21148 Nodh American Randomized Trial of Single-Triple Capsule (Bismuth Subcitrate, Metrooidazole, Tetracycline) plus Omeprazole vs. Omeprazole, Amoxicillin, and ClsdU.myde ~ H. Pytod Eradication Loren Laine, U S C Sch of Medicine, Los Angeles, CA; Richard H. Hunt, McMaster Univ, Hamilton Canada; Hala M. T. EI-Zimaity, Michael S. Osato, Baylor Coil of Medicine, Houston, TX; Jean Spenard, Axcan Pharma, Mont St-Hilaire Canada Randomizedtrials of PPI-bismuth-hased quadruple therapy or of bismuth subcitrate have not been done in the U.S., nor has the effect of metronidazole resistance on H. pylori (HP) eradication been widely studied in U.S. trials. We studied quadruple therapy using a new single-triple capsule containing bismuth subcitrate. METHODS: Patients with duodenal ulcer (OU) (active or documented by EGD or x-ray in past 5 yrs) and HP infection (by C-13 urea breath test plus histology or culture) were randomly assigned to a lO-day course of OBMT (single-triple capsule (Helicide~, containing bismuth subcitrate 40rag, metronidazole 125mg, tetracycline 125mg) 3 qid + omeprazole 2Brag bid) or OAC (omeprazole 20rag, amoxicilfin lg, clarithromycin 500rag, all bid). Two negative breath tests, > 1 mo and > 2 mo after end of therapy, were required to confirm eradication. If a post-therapy breath test was positive, repeat EGD was done for agar dilution susceptibility testing. Intent-to-treet (ITT) analysis included all patients with documented DO and HP (N = 277); per protocol analysis included ITT patients with breath test data available and no substantive protocol violation (N =250). RESULTS (SEE TABLE): Mean age in the I1-I group was 47 yrs and 39% were women. Baseline HP resistance rates were 39% for metmnidazole and 11% for clarithmmycin. Only 3 patients (2 in OAC, 1 in OBMT) withdrew due to adverse events. CONCLUSIONS:The singletriple capsule OBMT regimen is as efficacious as the widely used PPI triple therapy. This OBMT therapy overcomes HP metronidazole resistance, which is present in -40% of North ~ n OU pat.~nts.
2946 Assessment of Helicobacter pylori Infection in Primary Care; Whidt Test to Uu? Catherine F. Weijnen, Nlek J. De Wit, Mattijs E. Numans, Julius Ctr for Gen Practice and Patient Oriented Rese, Utrecht Netherlands; Ernst J. Kuipers, Dept of Gastroenterology Erasmus Univ Medical C, Rotterdam Netherlands; Amo W. Hoes, Theo J. Verheij, Julius Ctr for Gen Practice and Patient Oriented Rese, Utrecht Netherlands Background: As H py/ori(Hp)intection plays a major role in peptic ulcer disease, testing for Hp may contribute to management of dyspepsia in primary care (PC). Although nun-invasive Hp tests (i.e. tests not requiring endoscopy) are available,comparative validation studies in PC applying an optimal gold standard are virtually lacking. Aim: To determine test characteristics of non-invasive Hp tests in a PC population. Methods: Three different non-invasive tip tests (whole blood test, ELISA and carbon urea breath test (CUBT)) were evaluatedin the PC setting and validated against a gold standard including histology and a rapid urease test in gastric biopsies. All test characteristics were determined, but emphasis was laid on the positive predictive value (PPV) and negative predictive value (NPV) as Hp infection rate in PC is low and treatment initiation critically depends on the test result. Results: For 136 patients presenting with dyspepsia lasting > 2 weeks in PC complete data were available. Test characteristics are shown in the table below. The PPV was highest in the CUBT. In a subgroup with low Hp infection rate (the infection rate in PC is low and is expected to further decrease in the near future) the ELISA perfumed less well than the CUBT (PPV 75% vs 83%). The NPV of ELISA and CUBT were comparable. Conclusions: Diagnostic performance of the whole blood test was poor. Both ELISA and CUBTshowed acceptabletest characteristica. The CUBT performs best in all groups of patients (independent of Hp infection rate) and should be the test of choice for PC, in spite of it's higher costs.
Intent-to-TreatAnalyses All Patients M-Sensitive M-Re~dstant
C-SensJ~ve C..Reshdmt
PPV NPV Sensitivity Specificity
71.4 (47.8-88.7) 73.8 (65.3-82.3) 35.7 (21.6-52) 92.7 (84.7-97.3)
83.3 (69.8-92.5) 96 (88.8-99.2) 93 (80.9-98.5) 90 (81 2-95.6)
OBMT OAC 115/125(92%) 110/125(88%) 63/66(95%) .... 37/43(86%) --85/91 (93%) -3/12 (25%)*
2949
Triple Therapy with Panioprazole, Metronidazole and Amoxicillin for the Eradication of Hellcobaofer pylod in Patients with Duodenal Ulcer.
(n=t~) ELISA (Cl)
OAC 110/138(80%) ----85/99(86%) 3/13 (23%)*
Analyses
• p < O001, C-Sensitivevs. C-Resistant M = Metronidazote C = Clarithromycin
Table 1: Non-invasiveHp test characteristicsin the Primary Care sethn9 vs gold standard Whoteblood test (cl)
116/139(83%) 63/73 (86%) 38/49(78%)
Per-P~
Karsten Lauritsen, 0dense Univ Hosp, Odense Denmark; Susanne Hartzen, Dept of Clin Microbiology, Hillerod Denmark; Leue Hendel, Private Practice, Birkerod Denmark; RolfRoland link, Private Practice, Freising Germany
CUBT (CI) .....
High Helicobacter pylori (H.p.) eradication and duodenal ulcer (DU) healing rates have been published using pantoprazole based triple therapy, but data are limited in populations with a considerable metronidazole resistance. This study aimed to investigate the efficacy and tolerability of two different treatments with pantoprazole, metmnidazole and amoxicillin to eradicate H.p. in patients with DU. Methods: Open, multicentre, randomized trial carried out in Denmark and Germany. A total of 523 patients with endoscopically confirmed DU (5-20 mm diameter) and with a positive H.p. rapid urease test were allocated at random to treatment with either pantoprazole 40 mg b.i.d., amoxicillin 1000 mg b.i.d, and metronidazole 500 mg b.i.d. (PAM2), or pantoprazole 40 mg b.i.d., amoxicillin 750 mg t.i.d, and metronidazole 400 mg t.i.d. (PAM-3) for 7 days. H.p. infection was confirmed by a 13C-urea breath test (UBT) and antrum and corpus biopsies were cultured for H.p. Isolates were tested for their susceptibilities to amoxicillin and metmnidazole. After a treatment free period of 5 weeks the UBT and endoscopy with biopsies for culture were repeated.Eradication was defined by a negative UBT and culture. Results: The H.p. eradication rates (per protocol-cohort) were 73% and 77% for the PAM-2 and PAM-3 groups, respectively (ns). At baseline, resistance to metronidazole was found in 48% of patients and to amoxicillin in 0%. Eradication rates of 89% (PAM-2) to 94% (PAM3) and 50% (PAM-2) to 60% (PAM-3) were achieved in patients sensitive and resistant to metmnidazole, respectively. During the course of the study the development of newly resistant strains against metmnidazole was observed in 7 patients. DU healing rates after 6 weeks were 95% (PAM-2) and 90% (PAM-3), respectively. Early symptom relief occurred in both groups, and the treatments were well tolerated and associated with a high compliance.
87.8 (73.8-95.9) 95.9 (88.6-99.2) 92.3 (79.1-98.4) 93.4 (85.3-97.8)
PPV: positive predictivevalue; NPV: negativepredictivevalue (95% confidenceinterval)
2947 A Novel Method for Isolation of Helicobaoferpylori from Contaminated Human and Environmental Specimens Qunsheng Song, Centers for Disease Control and Prevention, Emory Univ, Atlanta, GA; Gerald W. Zirnstein, Bala Swaminathan, Benjamin D. Gold, Centers for Disease Control and Prevention, Atlanta, GA BACKGROUNDS:Previous attempts to isolate Helicobacterpylorifrom extra-gastric sites (e.g., saliva) using selective media enrichment and plating techniques have not been successful due, in part, to overgrowth of H. pylori by other microorganisms. AIM: To develop a new
A-580
not treat based on a positive result. Most use appropriate combination regimens although knowledge of antibiotic resistance is suboptimal.
2945
Hellcobacter pylori (Hp) Infection Plays a Crucial Role in the Majority of Alropbi¢ Body Gastritis (ABG) Patients Bruno Annibale, Edith Lahner, Cristina Grossi, Univ La Sapienza, Rome Italy; Riccardo Negrini, Spedali Civili, Brescia Italy; Pietro Caruana, Cesare Bordi, Univ, Parma Italy; Gabriele Capurso, Gianfranco Delle Fave, Univ La Sapienza, Rome Italy Background:ABG is characterizedby atrophy of oxyntic mucosa, hypo/achlorbydrla and fasting hypergastrinemia. It is now apparent that Hp may be involved in the induction of ABG. Hp infection may be detected by histology in a small proportion of ABG patients, but it has been recently suggested that in ABG patients the presence of circulating antibodies against Hp could indicate active infection too. Aim:to investigate the prevalence of Hp infection on the basis of histology and serology, in ABG patients. Patients:150 consecutive ABG outpatients (991:/51M, aged 22-83)diagnosed by a screening program performed on subjects with unexplained microcytic (n = 65) or macrocytic (n = 68)anemia or long-standing dyspepsia (n = 19). Methods:All patients had assesssment of monoclonal IgGHp and PC antibodies, fasting gastrin levels and gastroscopy with antrai (n = 3) and corporal (n = 3) biopsies. Gastritis was e s s e ~ according to the updated Sydney System. Results:24.6% of patients were Hp negative both at histology and serology (Group A), 52.7% were negativeat histology but positive at samlogy(Group B), 22.6% had histology positive for Hp (Group C).IgGHp levels (U/ml)were significantly different among the 3 groups, being the median respectively for groups A,B and C: 180 (0435), 2070 (465-75000) and 16350 (345-75000). There was also a clear gradient for the mean corporal atrophy (Group A> Group B> Group C)which was significantly higher in group A compared to B(2.75_+0.09 vs 2.43_+0.08; p<0.05)and in group B compared to C (1.79_+0.11; p<0.001). Corporal atrophy resulted correlated directly with PC Ab titer (r=0.04791; p<0.05) and inversely with IgGHp (r-0.2322; p<0.0001). Pernicious anemia was observed respectively in 75.6%, 45.6% and 11.8% in Groups A,B and C. Conclusions:This study demonstrates that Hp infection can be detected in 2/3 of ABG patients performing both histological and serological assessment. The observed correlation between the progression of corporal atrophy and both the increase of PC Ab titer and the decrease of IgGHp, strongly suggests that Hp infection is related with the induction of the oxyntic damage.
21148 Nodh American Randomized Trial of Single-Triple Capsule (Bismuth Subcitrate, Metrooidazole, Tetracycline) plus Omeprazole vs. Omeprazole, Amoxicillin, and ClsdU.myde ~ H. Pytod Eradication Loren Laine, U S C Sch of Medicine, Los Angeles, CA; Richard H. Hunt, McMaster Univ, Hamilton Canada; Hala M. T. EI-Zimaity, Michael S. Osato, Baylor Coil of Medicine, Houston, TX; Jean Spenard, Axcan Pharma, Mont St-Hilaire Canada Randomizedtrials of PPI-bismuth-hased quadruple therapy or of bismuth subcitrate have not been done in the U.S., nor has the effect of metronidazole resistance on H. pylori (HP) eradication been widely studied in U.S. trials. We studied quadruple therapy using a new single-triple capsule containing bismuth subcitrate. METHODS: Patients with duodenal ulcer (OU) (active or documented by EGD or x-ray in past 5 yrs) and HP infection (by C-13 urea breath test plus histology or culture) were randomly assigned to a lO-day course of OBMT (single-triple capsule (Helicide~, containing bismuth subcitrate 40rag, metronidazole 125mg, tetracycline 125mg) 3 qid + omeprazole 2Brag bid) or OAC (omeprazole 20rag, amoxicilfin lg, clarithromycin 500rag, all bid). Two negative breath tests, > 1 mo and > 2 mo after end of therapy, were required to confirm eradication. If a post-therapy breath test was positive, repeat EGD was done for agar dilution susceptibility testing. Intent-to-treet (ITT) analysis included all patients with documented DO and HP (N = 277); per protocol analysis included ITT patients with breath test data available and no substantive protocol violation (N =250). RESULTS (SEE TABLE): Mean age in the I1-I group was 47 yrs and 39% were women. Baseline HP resistance rates were 39% for metmnidazole and 11% for clarithmmycin. Only 3 patients (2 in OAC, 1 in OBMT) withdrew due to adverse events. CONCLUSIONS:The singletriple capsule OBMT regimen is as efficacious as the widely used PPI triple therapy. This OBMT therapy overcomes HP metronidazole resistance, which is present in -40% of North ~ n OU pat.~nts.
2946 Assessment of Helicobacter pylori Infection in Primary Care; Whidt Test to Uu? Catherine F. Weijnen, Nlek J. De Wit, Mattijs E. Numans, Julius Ctr for Gen Practice and Patient Oriented Rese, Utrecht Netherlands; Ernst J. Kuipers, Dept of Gastroenterology Erasmus Univ Medical C, Rotterdam Netherlands; Amo W. Hoes, Theo J. Verheij, Julius Ctr for Gen Practice and Patient Oriented Rese, Utrecht Netherlands Background: As H py/ori(Hp)intection plays a major role in peptic ulcer disease, testing for Hp may contribute to management of dyspepsia in primary care (PC). Although nun-invasive Hp tests (i.e. tests not requiring endoscopy) are available,comparative validation studies in PC applying an optimal gold standard are virtually lacking. Aim: To determine test characteristics of non-invasive Hp tests in a PC population. Methods: Three different non-invasive tip tests (whole blood test, ELISA and carbon urea breath test (CUBT)) were evaluatedin the PC setting and validated against a gold standard including histology and a rapid urease test in gastric biopsies. All test characteristics were determined, but emphasis was laid on the positive predictive value (PPV) and negative predictive value (NPV) as Hp infection rate in PC is low and treatment initiation critically depends on the test result. Results: For 136 patients presenting with dyspepsia lasting > 2 weeks in PC complete data were available. Test characteristics are shown in the table below. The PPV was highest in the CUBT. In a subgroup with low Hp infection rate (the infection rate in PC is low and is expected to further decrease in the near future) the ELISA perfumed less well than the CUBT (PPV 75% vs 83%). The NPV of ELISA and CUBT were comparable. Conclusions: Diagnostic performance of the whole blood test was poor. Both ELISA and CUBTshowed acceptabletest characteristica. The CUBT performs best in all groups of patients (independent of Hp infection rate) and should be the test of choice for PC, in spite of it's higher costs.
Intent-to-TreatAnalyses All Patients M-Sensitive M-Re~dstant
C-SensJ~ve C..Reshdmt
PPV NPV Sensitivity Specificity
71.4 (47.8-88.7) 73.8 (65.3-82.3) 35.7 (21.6-52) 92.7 (84.7-97.3)
83.3 (69.8-92.5) 96 (88.8-99.2) 93 (80.9-98.5) 90 (81 2-95.6)
OBMT OAC 115/125(92%) 110/125(88%) 63/66(95%) .... 37/43(86%) --85/91 (93%) -3/12 (25%)*
2949
Triple Therapy with Panioprazole, Metronidazole and Amoxicillin for the Eradication of Hellcobaofer pylod in Patients with Duodenal Ulcer.
(n=t~) ELISA (Cl)
OAC 110/138(80%) ----85/99(86%) 3/13 (23%)*
Analyses
• p < O001, C-Sensitivevs. C-Resistant M = Metronidazote C = Clarithromycin
Table 1: Non-invasiveHp test characteristicsin the Primary Care sethn9 vs gold standard Whoteblood test (cl)
116/139(83%) 63/73 (86%) 38/49(78%)
Per-P~
Karsten Lauritsen, 0dense Univ Hosp, Odense Denmark; Susanne Hartzen, Dept of Clin Microbiology, Hillerod Denmark; Leue Hendel, Private Practice, Birkerod Denmark; RolfRoland link, Private Practice, Freising Germany
CUBT (CI) .....
High Helicobacter pylori (H.p.) eradication and duodenal ulcer (DU) healing rates have been published using pantoprazole based triple therapy, but data are limited in populations with a considerable metronidazole resistance. This study aimed to investigate the efficacy and tolerability of two different treatments with pantoprazole, metmnidazole and amoxicillin to eradicate H.p. in patients with DU. Methods: Open, multicentre, randomized trial carried out in Denmark and Germany. A total of 523 patients with endoscopically confirmed DU (5-20 mm diameter) and with a positive H.p. rapid urease test were allocated at random to treatment with either pantoprazole 40 mg b.i.d., amoxicillin 1000 mg b.i.d, and metronidazole 500 mg b.i.d. (PAM2), or pantoprazole 40 mg b.i.d., amoxicillin 750 mg t.i.d, and metronidazole 400 mg t.i.d. (PAM-3) for 7 days. H.p. infection was confirmed by a 13C-urea breath test (UBT) and antrum and corpus biopsies were cultured for H.p. Isolates were tested for their susceptibilities to amoxicillin and metmnidazole. After a treatment free period of 5 weeks the UBT and endoscopy with biopsies for culture were repeated.Eradication was defined by a negative UBT and culture. Results: The H.p. eradication rates (per protocol-cohort) were 73% and 77% for the PAM-2 and PAM-3 groups, respectively (ns). At baseline, resistance to metronidazole was found in 48% of patients and to amoxicillin in 0%. Eradication rates of 89% (PAM-2) to 94% (PAM3) and 50% (PAM-2) to 60% (PAM-3) were achieved in patients sensitive and resistant to metmnidazole, respectively. During the course of the study the development of newly resistant strains against metmnidazole was observed in 7 patients. DU healing rates after 6 weeks were 95% (PAM-2) and 90% (PAM-3), respectively. Early symptom relief occurred in both groups, and the treatments were well tolerated and associated with a high compliance.
87.8 (73.8-95.9) 95.9 (88.6-99.2) 92.3 (79.1-98.4) 93.4 (85.3-97.8)
PPV: positive predictivevalue; NPV: negativepredictivevalue (95% confidenceinterval)
2947 A Novel Method for Isolation of Helicobaoferpylori from Contaminated Human and Environmental Specimens Qunsheng Song, Centers for Disease Control and Prevention, Emory Univ, Atlanta, GA; Gerald W. Zirnstein, Bala Swaminathan, Benjamin D. Gold, Centers for Disease Control and Prevention, Atlanta, GA BACKGROUNDS:Previous attempts to isolate Helicobacterpylorifrom extra-gastric sites (e.g., saliva) using selective media enrichment and plating techniques have not been successful due, in part, to overgrowth of H. pylori by other microorganisms. AIM: To develop a new
A-580