Background.
Although combinations of antibiotics and
antisecretory drugs are useful for treatment of
Helicobacter pylori infection, treatment failure is common.
The aim of this study was to evaluate the relation between
pretreatment antibiotic resistance and outcome
by using six different treatment regimens for
H. pylori
infection.
Patients and Methods.
Three hundred sixty-nine consecutive
H. pylori–
infected patients with dyspeptic
symptoms were enrolled in three consecutive randomized,
controlled, single-center clinical trials: trial A, 128
patients; trial B, 125 patients; trial C, 116 patients.
Treatments consisted of (A) a 15-day course of dual
therapy (omeprazole, 20 mg bid, and amoxicillin, 1 gm
bid, or clarithromycin, 500 mg tid) (OA vs OC); (B) a
7-day triple therapy of omeprazole, 20 mg bid, plus
metronidazole, 500 mg bid, and amoxicillin, 1,000 mg
bid, or clarithromycin, 500 mg tid (OMA vs OMC); or
(C) omeprazole, 20 mg bid, plus metronidazole, 500 mg
bid, plus tetracycline, 500 mg qid, or doxycycline, 100
mg tid (OMT vs OMD). Diagnostic endoscopy was
made in all patients before and 5 to 6 weeks after therapy.
Six biopsies were taken from each patient for histology,
rapid urease test, and
H. pylori
culture; antibiotic
susceptibility testing was performed using the
E-test method.
Results.
Overall cure rates were poor for both dual
therapies OA and OC (38% and 37%, respectively) and
for triple therapies OMA, OMC, and OMD (57%,
55%, and 58%, respectively). The OMT combination
was successful in 91% (95% confidence interval [CI],
80.4%–97%). Metronidazole resistance was present in
29.7% (95% CI, 24%–35%), amoxicillin resistance
was present in 26% (95% CI, 21%–32%), clarithromycin
resistance was present in 23.1% (95% CI, 18%–
29%), tetracycline resistance was present in 14% (95%
CI, 10%–20%), and doxycycline resistance was present
in 33.3% (95% CI, 21%–47%). Antibiotic resistance
markedly reduced the cure rates and accounted for
most of the poor results with the triple therapies: 89%
versus 23%; 77% versus 26%; 100% versus 60%; and
67% versus 23% for OMC, OMA, OMT, and OMD,
respectively. OMT appeared to be the best because of
the high success rate with metronidazole-resistant
H.pylori (71%) and in low-level tetracycline resistance.
Conclusions.
Pretreatment antibiotic-resistant
H. pylori can, in part, explain the low cure rate of the infection and the variability in outcome in reported trial