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Has Hericobacter pylori eradication for large gastric ulcers been overrated?
April 2000
AGAA497
2668
2670
OMEPRAZOLE COMBINED WITH AMOXICILLIN AND CLARITHROMYCIN IN THE ERADICATION OF HELICOBACTER rvLORI IN CHILDREN WITH GASTRITIS: A PROSPECTIVE RANDOMISED DOUBLE-BLIND TRIAL.
ANTIBIOTIC SUSCEPTIBILITY PATTERNS IN NORTH AND MIDDLE JAPAN: CLARITHROMYCIN RESISTANCE HAS REACHED 18.7% IN JAPAN.
Frederic Gottrand, Nicolas Kalach, Claire Spyckerelle, Jean-Francois Mougenot, Jean-Philippe Girardet, Chantal Lenaerts, Jacques Sarles, Alain Lachaux, Alain Morali, Christophe Dupont, Chantal Maurage, Philippe Barthelemy, Lille, France; Creil, France; Paris, France; Arniens, France; Marseille, France; Lyon, France; Nancy, France; Tours, France; RueilMalmaison, France. The combination omeprazole[O]-amoxicillin[A]-clarithromycin[C] for one week is a reference treatment for the eradication of Helicobacter pylori (H. pylori) in adults. The aim of this multicenter prospective, randomised, double-blind study was to assess the efficacy of omeprazole combined with amoxicillin and clarithromycin in the treatment of H. pylori gastritis in children. Methods: 73 children were included (Mean age: 10.8 years; 3.3 to 15.4). Inclusion criteria were presence of dyspeptic symptoms, no gastroduodenal ulcer at upper-Gl endoscopy, gastritis at histopathological examination and a positive urease test (or another positive test for the presence of H. pylori). Patients were randomised to one of the following treatments for 7 days: 1) OAC: omeprazole: 10 mg bid (15 to 30kg) or 20 mg bid (>30 kg) + amoxicillin 25 mglkg bid + clarithromycin 7.5 mglkg bid; 2) AC: placebo bid + amoxicillin 25 mglkg bid + clarithromycin 7.5 mglkg bid. H. pylori status was assessed before and 4 weeks after eradication with 13-C urea breath test (UBT). Intent to treat analysis (lIT) included 63 patients with a positive UBT. Patients whose final H. pylori status was not assessed were considered as failures. Per protocol analysis (PP) included 53 patients, excluding those with major violation or without assessment of final H. pylori status. Results : Eradication rates were significantly higher in OAC group as compared to AC group (see table below).The most frequently reported adverse events were diarrhoea (n=7) and abdominal pain (n=5). Conclusion: This study shows the important contribution of omeprazole to successful eradication of H. pylori with one-week OAC triple therapy in children with gastritis. Eradication rates obtained in these children are similar to those observed in adults in France.
Mototosugu Kato, Masahiro Asaka, Jae 1. Kim, Yoshio Yamaoka, Rita Reddy, Fouad A. El-Zaatari, Michael S. Osato, David Y. Graham, Dong H. Kwon, Hokkaido Univ, Sapporo, Japan; VAMC and Baylor Coli of Medicine, Houston, TX.
Eradication %
OAC
AC
Difference (95%Cq
P
rrr
74.2 [58.?; 89.6) 80.0 [64.3; 95.?)
9.4 [0; 19.5) 10.? [0; 222]
648 [46.4; 83.2] 693 [49.9; 88.?]
<0.01
Background: Antibiotic resistance of Helicobacter pylori is problematic because treatment for H. pylori infection is often started on an empirical basis. If the infected strains are resistant to the antibiotics selected successful eradication is compromised. Aim: To assess the primary metronidazole and clarithromycin resistance rates among H. pylori isolates from two different geographic regions in Japan, Sapporo in the north island and Kyoto in central Japan. Methods: H. pylori isolates from 388 Japanese patients (247 males and 141 females, median age 51 year, range 21-85 years) from Sapporo (283 patients) and Kyoto (105 patients), who underwent endoscopy between January 1996 and February 1999 were tested for antibiotic susceptibility. Endoscopic diagnosis included chronic gastritis (80 patients), duodenal ulcer disease (118 patients), gastric ulcer disease (139 patients), and gastric cancer (51 patients). H. pylori isolated from gastric mucosal biopsy specimens were tested for metronidazole, amoxicillin, and clarithromycin susceptibility by agar dilution. Isolates were considered resistant when the MIC value was >8 mg/L for metronidazole, > I mg/L for clarithromycin and> 1 mglL for amoxicillin. Results: Overall primary resistance to metronidazole and clarithromycin were 12.4% and 12.9%, respectively. None of the isolates were resistant to amoxicillin. The metronidazole resistance rate was significantly higher in Kyoto than in Sapporo (23.8% vs. 8.1%, p<0.05). There was no difference in clarithromycin resistance between the two areas. The prevalence of primary clarithromycin resistance increased from 9.1% in 1996 to 18.7% in 1998-99 in both the Sapporo and Kyoto areas. The prevalence of metronidazole resistance did not change significantly in either region. There were no significant differences in metronidazole and clarithromycin resistance according to age, sex and disease presentation. Conclusions: a) There was a regional difference in metronidazole resistance in Japan; and b) Clarithromycin resistance rates have increased to a point that the effectiveness of clarithromycin containing triple therapies will likely be compromised in Japan.
<0.01
2671
PP
INCREASING HEUCOBACTER PYLORI RESISTANCE TO MET· RONIDAZOLE, CLARITHROMYCIN AND TETRACYCLINE.
2669
HAS HEUCOBACTER PYLORI ERADICATION FOR LARGE GASTRIC ULCERS BEEN OVERRATED? Kazuhide Higuchi, Tetsuo Arakawa, Yasuhiro Fujiwara, Kazunari Tominaga, Toshio Watanabe, Toshiyuki Uchida, Tetsuo Kuroki, Osaka City Univ Med Sch, Osaka, Japan. Few studies have reported the proportion of patients whose gastric ulcers heal when the initial therapy to eradicate H. pylori is for only 1 week. This prospective study evaluated the effects of the so-called new triple therapy done for I week, compared with the effects of the usual therapy with a proton pump inhibitor (PPI). Methods: Patients with gastric ulcers found by endoscopy and with H. pylori infection confirmed by histological results and culture were assigned radomly to a treatment group. Group 1 was given two antibacterial agents (1500 mg of amoxiciline and 800 mg of clarisromycin and a PPI (either 30 mg of ransoprazole or 40 mg of rabeprazole) daily for one week. Group 2 was given a PPI for 8 weeks. Follow-up endoscopy was done after 8 weeks. At the same time, histology, culture, a [13C]urea breath test were examined. Results: Between April 1997 and April 1999, 110 patients with gastric ulcers and with H. pylori infection were studied; 61 patients were assigned to antibacterial therapy, and 59 were assigned to treatment with a PPJ. The eradication rate with antibacterial therapy was 84% (51/61) by intention-totreat analysis, and 89% (51/57) by per-protocol analysis, but that in the PPI group was 0%. The healing rate with triple therapy was lower for large gastric ulcers than with the conventional therapy (table). Conclusions: In patients infected with H. pylori who have gastric ulcers not caused by the use of nonsteroidal anti-inflammatory drugs, the healing rate for large ulcers with antibacterial therapy only was lower than might be expected from reports to date. For healing of large gastric ulcers, an acid-suppressive drug such as a PPI is needed. Rate ofulcer healing 8weeks after start oftreatments Patients healedltotal patients (%) by Ulcer diameter, mm 5to< 10 10to< 15 ~ 15
Total 'Mann-Whitney U-test
Triple therapy
PPI
Pvalue'
16/18 (89%) 13/24 (54%) 1/19(5%) 30/61 (49%)
15/15(100%) 17/22 (77%) 17/22 (77%) 49/59 (83%)
0.18 010 <0.001 <0.001
Jae J. Kim, Rita Reddy, Siddharta G. Reddy, Fouad A. El-Zaatari, Michael S. Osato, J. G. Kim, David Y. Graham, Dong H. Kwon, VAMC and Baylor Coli of Medicine, Houston, TX; Guro Hosp Korea Univ, Seoul, South Korea. Background: The high prevalence of antimicrobial resistance in H. pylori makes it critical to know the local antibiotic resistance patterns in order to prevent failure of empiric therapy. Furthermore, there has been a debate whether the susceptibility test results obtained from antrum are representative of that of H. pylori in the stomach. Aim: To assess the primary antibiotic resistance rates in Korean H. pylori isolates and to determine the consistency of drug-susceptibility patterns of isolates obtained from antrum and body of the same patients. Methods: H. pylori isolates from 459 patients (314 males and 145 females, median age 45 year, range 16-82 years) who underwent endoscopy (in Guro Hospital, Seoul, Korea) between September 1993 and September 1999, were tested for drug susceptibility. 109 patients had chronic gastritis, 224 had peptic ulcer diseases, and 126 had gastric cancer. H. pylori were isolated from gastric mucosal biopsy specimens and the recovered isolates were tested for metronidazole, clarithromycin, tetracycline, and amoxicillin susceptibility by agar dilution method. Isolates were considered resistant when the MIC value was >8 mgIL for metronidazole, > 1 mg/L for amoxicillin, >2 mgIL for tetracycline, and> 1 mgIL for clarithromycin. Results: Overall primary resistance to metronidazole, clarithromycin and tetracycline were 40.5%, 5.9% and 5.2%, respectively. 2 patients had amoxicillin resistant Hp. The prevalence of primary resistance to metronidazole, clarithromycin and tetracycline has increased (e.g., from 33.3%, 4.5% and 3.0%, respectively in 1993-94 to 47.7%,7.7%, and 7.7%, respectively in 1998-99). There was no significant difference in metronidazole, clarithromycin and tetracycline resistance according to age, sex or disease except for a high prevalence of metronidazole resistance in chronic gastritis compared to gastric cancer (48.6% versus 34%, p<0.05). For metronidazole susceptibility, fourteen (7.1%) of 196 patients who had both antral and body isolates had susceptible antral isolates but resistant fundus isolates and fifteen patients (7.7%) had susceptible body isolates but resistant antral isolates. The maximum difference with clarithromycin was 2% and 2.6% for tetracycline susceptibility. Conclusion: Metronidazole, clarithromycin and tetracycline resistant H. pylori have increased over the last 4 to 5 years in Korea. Biopsies from both the antrum and body are necessary for representative metronidazole susceptibility testing.
AGAA497
2668
2670
OMEPRAZOLE COMBINED WITH AMOXICILLIN AND CLARITHROMYCIN IN THE ERADICATION OF HELICOBACTER rvLORI IN CHILDREN WITH GASTRITIS: A PROSPECTIVE RANDOMISED DOUBLE-BLIND TRIAL.
ANTIBIOTIC SUSCEPTIBILITY PATTERNS IN NORTH AND MIDDLE JAPAN: CLARITHROMYCIN RESISTANCE HAS REACHED 18.7% IN JAPAN.
Frederic Gottrand, Nicolas Kalach, Claire Spyckerelle, Jean-Francois Mougenot, Jean-Philippe Girardet, Chantal Lenaerts, Jacques Sarles, Alain Lachaux, Alain Morali, Christophe Dupont, Chantal Maurage, Philippe Barthelemy, Lille, France; Creil, France; Paris, France; Arniens, France; Marseille, France; Lyon, France; Nancy, France; Tours, France; RueilMalmaison, France. The combination omeprazole[O]-amoxicillin[A]-clarithromycin[C] for one week is a reference treatment for the eradication of Helicobacter pylori (H. pylori) in adults. The aim of this multicenter prospective, randomised, double-blind study was to assess the efficacy of omeprazole combined with amoxicillin and clarithromycin in the treatment of H. pylori gastritis in children. Methods: 73 children were included (Mean age: 10.8 years; 3.3 to 15.4). Inclusion criteria were presence of dyspeptic symptoms, no gastroduodenal ulcer at upper-Gl endoscopy, gastritis at histopathological examination and a positive urease test (or another positive test for the presence of H. pylori). Patients were randomised to one of the following treatments for 7 days: 1) OAC: omeprazole: 10 mg bid (15 to 30kg) or 20 mg bid (>30 kg) + amoxicillin 25 mglkg bid + clarithromycin 7.5 mglkg bid; 2) AC: placebo bid + amoxicillin 25 mglkg bid + clarithromycin 7.5 mglkg bid. H. pylori status was assessed before and 4 weeks after eradication with 13-C urea breath test (UBT). Intent to treat analysis (lIT) included 63 patients with a positive UBT. Patients whose final H. pylori status was not assessed were considered as failures. Per protocol analysis (PP) included 53 patients, excluding those with major violation or without assessment of final H. pylori status. Results : Eradication rates were significantly higher in OAC group as compared to AC group (see table below).The most frequently reported adverse events were diarrhoea (n=7) and abdominal pain (n=5). Conclusion: This study shows the important contribution of omeprazole to successful eradication of H. pylori with one-week OAC triple therapy in children with gastritis. Eradication rates obtained in these children are similar to those observed in adults in France.
Mototosugu Kato, Masahiro Asaka, Jae 1. Kim, Yoshio Yamaoka, Rita Reddy, Fouad A. El-Zaatari, Michael S. Osato, David Y. Graham, Dong H. Kwon, Hokkaido Univ, Sapporo, Japan; VAMC and Baylor Coli of Medicine, Houston, TX.
Eradication %
OAC
AC
Difference (95%Cq
P
rrr
74.2 [58.?; 89.6) 80.0 [64.3; 95.?)
9.4 [0; 19.5) 10.? [0; 222]
648 [46.4; 83.2] 693 [49.9; 88.?]
<0.01
Background: Antibiotic resistance of Helicobacter pylori is problematic because treatment for H. pylori infection is often started on an empirical basis. If the infected strains are resistant to the antibiotics selected successful eradication is compromised. Aim: To assess the primary metronidazole and clarithromycin resistance rates among H. pylori isolates from two different geographic regions in Japan, Sapporo in the north island and Kyoto in central Japan. Methods: H. pylori isolates from 388 Japanese patients (247 males and 141 females, median age 51 year, range 21-85 years) from Sapporo (283 patients) and Kyoto (105 patients), who underwent endoscopy between January 1996 and February 1999 were tested for antibiotic susceptibility. Endoscopic diagnosis included chronic gastritis (80 patients), duodenal ulcer disease (118 patients), gastric ulcer disease (139 patients), and gastric cancer (51 patients). H. pylori isolated from gastric mucosal biopsy specimens were tested for metronidazole, amoxicillin, and clarithromycin susceptibility by agar dilution. Isolates were considered resistant when the MIC value was >8 mg/L for metronidazole, > I mg/L for clarithromycin and> 1 mglL for amoxicillin. Results: Overall primary resistance to metronidazole and clarithromycin were 12.4% and 12.9%, respectively. None of the isolates were resistant to amoxicillin. The metronidazole resistance rate was significantly higher in Kyoto than in Sapporo (23.8% vs. 8.1%, p<0.05). There was no difference in clarithromycin resistance between the two areas. The prevalence of primary clarithromycin resistance increased from 9.1% in 1996 to 18.7% in 1998-99 in both the Sapporo and Kyoto areas. The prevalence of metronidazole resistance did not change significantly in either region. There were no significant differences in metronidazole and clarithromycin resistance according to age, sex and disease presentation. Conclusions: a) There was a regional difference in metronidazole resistance in Japan; and b) Clarithromycin resistance rates have increased to a point that the effectiveness of clarithromycin containing triple therapies will likely be compromised in Japan.
<0.01
2671
PP
INCREASING HEUCOBACTER PYLORI RESISTANCE TO MET· RONIDAZOLE, CLARITHROMYCIN AND TETRACYCLINE.
2669
HAS HEUCOBACTER PYLORI ERADICATION FOR LARGE GASTRIC ULCERS BEEN OVERRATED? Kazuhide Higuchi, Tetsuo Arakawa, Yasuhiro Fujiwara, Kazunari Tominaga, Toshio Watanabe, Toshiyuki Uchida, Tetsuo Kuroki, Osaka City Univ Med Sch, Osaka, Japan. Few studies have reported the proportion of patients whose gastric ulcers heal when the initial therapy to eradicate H. pylori is for only 1 week. This prospective study evaluated the effects of the so-called new triple therapy done for I week, compared with the effects of the usual therapy with a proton pump inhibitor (PPI). Methods: Patients with gastric ulcers found by endoscopy and with H. pylori infection confirmed by histological results and culture were assigned radomly to a treatment group. Group 1 was given two antibacterial agents (1500 mg of amoxiciline and 800 mg of clarisromycin and a PPI (either 30 mg of ransoprazole or 40 mg of rabeprazole) daily for one week. Group 2 was given a PPI for 8 weeks. Follow-up endoscopy was done after 8 weeks. At the same time, histology, culture, a [13C]urea breath test were examined. Results: Between April 1997 and April 1999, 110 patients with gastric ulcers and with H. pylori infection were studied; 61 patients were assigned to antibacterial therapy, and 59 were assigned to treatment with a PPJ. The eradication rate with antibacterial therapy was 84% (51/61) by intention-totreat analysis, and 89% (51/57) by per-protocol analysis, but that in the PPI group was 0%. The healing rate with triple therapy was lower for large gastric ulcers than with the conventional therapy (table). Conclusions: In patients infected with H. pylori who have gastric ulcers not caused by the use of nonsteroidal anti-inflammatory drugs, the healing rate for large ulcers with antibacterial therapy only was lower than might be expected from reports to date. For healing of large gastric ulcers, an acid-suppressive drug such as a PPI is needed. Rate ofulcer healing 8weeks after start oftreatments Patients healedltotal patients (%) by Ulcer diameter, mm 5to< 10 10to< 15 ~ 15
Total 'Mann-Whitney U-test
Triple therapy
PPI
Pvalue'
16/18 (89%) 13/24 (54%) 1/19(5%) 30/61 (49%)
15/15(100%) 17/22 (77%) 17/22 (77%) 49/59 (83%)
0.18 010 <0.001 <0.001
Jae J. Kim, Rita Reddy, Siddharta G. Reddy, Fouad A. El-Zaatari, Michael S. Osato, J. G. Kim, David Y. Graham, Dong H. Kwon, VAMC and Baylor Coli of Medicine, Houston, TX; Guro Hosp Korea Univ, Seoul, South Korea. Background: The high prevalence of antimicrobial resistance in H. pylori makes it critical to know the local antibiotic resistance patterns in order to prevent failure of empiric therapy. Furthermore, there has been a debate whether the susceptibility test results obtained from antrum are representative of that of H. pylori in the stomach. Aim: To assess the primary antibiotic resistance rates in Korean H. pylori isolates and to determine the consistency of drug-susceptibility patterns of isolates obtained from antrum and body of the same patients. Methods: H. pylori isolates from 459 patients (314 males and 145 females, median age 45 year, range 16-82 years) who underwent endoscopy (in Guro Hospital, Seoul, Korea) between September 1993 and September 1999, were tested for drug susceptibility. 109 patients had chronic gastritis, 224 had peptic ulcer diseases, and 126 had gastric cancer. H. pylori were isolated from gastric mucosal biopsy specimens and the recovered isolates were tested for metronidazole, clarithromycin, tetracycline, and amoxicillin susceptibility by agar dilution method. Isolates were considered resistant when the MIC value was >8 mgIL for metronidazole, > 1 mg/L for amoxicillin, >2 mgIL for tetracycline, and> 1 mgIL for clarithromycin. Results: Overall primary resistance to metronidazole, clarithromycin and tetracycline were 40.5%, 5.9% and 5.2%, respectively. 2 patients had amoxicillin resistant Hp. The prevalence of primary resistance to metronidazole, clarithromycin and tetracycline has increased (e.g., from 33.3%, 4.5% and 3.0%, respectively in 1993-94 to 47.7%,7.7%, and 7.7%, respectively in 1998-99). There was no significant difference in metronidazole, clarithromycin and tetracycline resistance according to age, sex or disease except for a high prevalence of metronidazole resistance in chronic gastritis compared to gastric cancer (48.6% versus 34%, p<0.05). For metronidazole susceptibility, fourteen (7.1%) of 196 patients who had both antral and body isolates had susceptible antral isolates but resistant fundus isolates and fifteen patients (7.7%) had susceptible body isolates but resistant antral isolates. The maximum difference with clarithromycin was 2% and 2.6% for tetracycline susceptibility. Conclusion: Metronidazole, clarithromycin and tetracycline resistant H. pylori have increased over the last 4 to 5 years in Korea. Biopsies from both the antrum and body are necessary for representative metronidazole susceptibility testing.