Incidence of secondary Helicobacter pylori resistance to antibiotics in treatment failures after 1-week proton pump inhibitor-based triple therapies: a prospective study.
BACKGROUND
Antibiotic-resistant Helicobacter pylori strains are becoming increasingly prevalent, although it is not clear to what extent the new resistant organisms will spread.


OBJECTIVE
To evaluate the incidence of secondary Helicobacter pylori resistance to metronidazole, clarithromycin and/or amoxycillin after one-week proton pump inhibitor based triple therapy failure in patients who were, before therapy infected with Helicobacter pylori strains susceptible to these antibiotics.


METHODS
Enrolled in the study were 97 consecutive Helicobacter pylori-positive subjects infected by Helicobacter pylori strains susceptible to metronidazole, clarithromycin and amoxycillin. Activity of tested antibiotics was determined by means of the E-test. Patients were treated for seven days with a proton pump inhibitor, omeprazole 20 mg twice daily or pantoprazole 40 mg once daily, plus clarithromycin 250 mg twice daily and metronidazole 250 mg four times daily; or with a proton pump inhibitor plus amoxycillin 1 g twice daily and clarithromycin 500 mg twice daily. Two months after completion of therapy, endoscopy and gastric biopsies for histology, rapid urease test and culture were repeated.


RESULTS
Four patients were dropped from the study Overall Helicobacter pylori cure rates expressed as both intention-to-treat and per-protocol analyses, were, respectively 80% (40/50) and 81.6% (40/49) with proton pump inhibitor, clarithromycin and metronidazole and 76.6% (36/47) and 81.8% (36/44) with proton pump inhibitor amoxycillin and clarithromycin. No significant differences were observed between the two treatments. Subjects in whom treatment failed were significantly younger and had less active ulcer than cured patients. Of treatment failures, 70.6% (12 out of 17 subjects) de veloped a secondary resistance to metronidazole (35.33% and/or clarithromycin (64.7%). Secondary antibiotic resistance occurred in 77. 8% of treatment failures treated with proton pump inhibitor, clarithromycin and metronidazole and in 62.5% of those treated with proton pump inhibitor, amoxycillin and clarithromycin. Considering all patients treated, the overall incidence of secondary metronidazole and/or clarithromycin resistance after therapy was reported in 12.9% of subjects (12 out of 93 treated patients).


CONCLUSIONS
Secondary Helicobacter pylori resistances to metronidazole and/or clarithromycin occurred in large percentages in patients with treatment failure after the one-week proton pump inhibitor-based triple therapies, proton pump inhibitor, clarithromycin and metronidazole and proton pump inhibitor, amoxycillin and clarithromycin. It is likely that new antibiotics or treatment strategies will be needed in the near future to successfully treat Helicobacter pylori infection.
Pilotto
A
A
Department of Geriatrics, S. Bortolo Hospital, Vicenza, Italy. alberto.pilotto@libero.it
Franceschi
M
M
Rassu
M
M
Leandro
G
G
Bozzola
L
L
Furlan
F
F
Di Mario
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000658:Amoxicillin / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017291:Clarithromycin / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology*; D016481:Helicobacter Infections / Q000175:diagnosis / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use; D011446:Prospective Studies; D054328:Proton Pump Inhibitors; D017211:Treatment Failure
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D005765:Gastrointestinal Agents; D054328:Proton Pump Inhibitors; D008795:Metronidazole; D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole