Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy.
OBJECTIVE
To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy.


METHODS
Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial.


RESULTS
Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (e.g., susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group.


CONCLUSIONS
These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains.


BACKGROUND
NCT02175901.
GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China.
Wei
W
Zhang
GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China.
Qi
Q
Chen
GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China.
Xiao
X
Liang
GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China.
Wenzhong
W
Liu
GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China.
Shudong
S
Xiao
Michael E. DeBakey VA Medical Center, and Baylor College of Medicine Houston, Houston, Texas, USA.
David Y
DY
Graham
GI Division, Renji Hospital, School of Medicine, Shanghai Jiao-Tong University, Shanghai Institution of Digestive Disease, Shanghai, China Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai, China.
Hong
H
Lu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001729:Bismuth / Q000627:therapeutic use*; D017291:Clarithromycin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D064747:Lansoprazole / Q000627:therapeutic use*; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D055815:Young Adult
D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D008795:Metronidazole; D000658:Amoxicillin; D017291:Clarithromycin; D001729:Bismuth