Combination amoxycillin and metronidazole with famotidine in the eradication of Helicobacter pylori--a randomized, double-blind comparison of a three times daily and twice daily regimen.
OBJECTIVE
To determine the efficacy of a three times daily (t.i.d.) versus a twice daily (b.i.d.) regimen of combination amoxycillin and metronidazole and famotidine in the eradication of Helicobacter pylori and the influence of metronidazole resistance on the outcome of treatment.


METHODS
Patients selected had unequivocal evidence of H. pylori infection based on the urease test, culture and histology and had either peptic ulcer disease or non-ulcer dyspepsia.


METHODS
The study was a comparative and double-blind study and patients were randomized to receive either amoxycillin 750 mg t.i.d. and metronidazole 500 mg t.i.d. for 12 days or amoxycillin 1000 mg b.i.d. and metronidazole 500 mg b.i.d. for 12 days. Both groups also received famotidine 40 mg for 6 weeks.


METHODS
Patients were assessed for successful eradication, defined as absence of bacteria in all tests, at least 4 weeks after completion of antibiotic therapy by repeat gastroscopy.


RESULTS
One hundred and twenty-nine patients were recruited for the study. Two patients defaulted follow-up, two patients were withdrawn from the study and six patients were found to be non-compliant with medications. The eradication rates of the t.i.d. regimen was higher than the b.i.d. regimen (per protocol (PP) analysis: 83.3% (50/60) vs. 76.3% (45/59), P=0.337; intention-to-treat (ITT) analysis: 78.5% (51/65) vs. 75.0% (48/64), P=0.642). Seventy-five patients had pre-treatment cultures checked for metronidazole resistance, 33 (44.0%) were found to be resistant. Acquired resistance occurred in 3/40 (7.5%) patients. Eradication rates of metronidazole-sensitive and metronidazole-resistant patients: t.i.d. regimen - 100% (17/17) and 88.2% (15/17), b.i.d. regimen - 19/21 (90.5%) and 11/15 (73.3%). Side effects were reported in up to 70% of patients but were mild and tolerable in the majority. Two patients were withdrawn from the study because of a fixed drug eruption in one and generalized macular rash in the other.


CONCLUSIONS
Combination amoxycillin and metronidazole is effective in eradicating H. pylori. There was a tendency for the t.i.d. regimen to be better than the b.i.d. regimen and for metronidazole-resistant infections to be associated with a lower eradication rate but these differences did not reach statistical significance.
Goh
K L
KL
Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Parasakthi
N
N
Chuah
S Y
SY
Toetsch
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000008:administration & dosage* / Q000009:adverse effects; D000994:Antitrichomonal Agents / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000627:therapeutic use*; D015738:Famotidine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects / Q000302:isolation & purification; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010406:Penicillins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D000994:Antitrichomonal Agents; D006635:Histamine H2 Antagonists; D010406:Penicillins; D008795:Metronidazole; D015738:Famotidine; D000658:Amoxicillin