NICE, FRANCE — Two different rifabutin-based, triple-therapy approaches proved to be safe and effective rescue therapies in two European trials involving patients with treatment-resistant Helicobacter pylori.
In primary care, first-line triple therapy has been shown to fail in up to 27% of patients. These failures are frequently due to metronidazole or clarithromycin resistance. Further, up to 75% of these infections are resistant to both drugs, Dr. Stephan Miehlke said at the 16th European Congress of Clinical Microbiology and Infectious Diseases.
Triple therapy with a proton pump inhibitor, rifabutin, and either amoxicillin or levofloxacin has been proven effective as salvage therapy. More recently, some physicians have undertaken first-line therapy with a proton pump inhibitor, moxifloxacin, and either clarithromycin or amoxicillin.
To assess this type of therapy, Dr. Miehlke and his associates treated 104 consecutive patients with H. pylori infections who were resistant to both metronidazole and clarithromycin by giving them esomeprazole 40 mg, moxifloxacin 400 mg, and rifabutin 300 mg orally once each morning for 7 days.
Indications for treatment included peptic ulcers (30%), functional dyspepsia/nonulcer dyspepsia (59%), and other diagnoses (11%). Two-thirds of the patients had a history of two or more previous treatment failures, and 25% had a known history of penicillin intolerance.
Follow-up endoscopy, including histology and H. pylori culture, was performed 6–8 weeks after treatment. Clinical failure was defined as at least one positive biopsy-based test or a positive urea breath test.
Four patients discontinued treatment prematurely because of adverse events, and two were lost to follow-up. Successful eradication of H. pylori infection was confirmed in 70 of the 86 patients (81%) for whom follow-up endoscopy was available.
In the 16 patients who were deemed treatment failures, posttreatment resistance to rifampicin was detected in 5 patients, and resistance to ciprofloxacin in 3. Minor adverse events occurred in 57% of patients and commonly included nausea, headache, and muscle pain.
Although secondary resistance can occur, the 1-week, once-daily therapy is safe, is at least as effective as quadruple therapy, and may be particularly useful for patients with an intolerance to penicillin, concluded Dr. Miehlke of the Technical University Hospital in Dresden, Germany.
Results from a second study he presented demonstrated that rifabutin-based triple therapy was comparable to high-dose dual therapy for treatment-resistant H. pylori, and that sequential therapy is both possible and effective.
In that study, 145 patients with H. pylori infection who were resistant to both metronidazole and clarithromycin were prospectively randomized to receive one of two regimens: either twice-daily therapy for 7 days with esomeprazole 20 mg, rifabutin 150 mg, and amoxicillin 1,000 mg; or thrice-daily therapy for 14 days with omeprazole 40 mg and amoxicillin 1,000 mg.
Indications for treatment included peptic ulcer disease (37%), nonulcer dyspepsia (46.6%), gastroesophageal reflux disease (2.7%), and other diagnoses (13.7%). Two-thirds of the patients (68%) had failed two or more previous treatment regimens.
Six patients discontinued treatment prematurely due to side effects, and three were lost to follow-up.
Eradication of H. pylori infection was achieved in 78% of triple-therapy patients (54/69) and 75% of high-dose, dual-therapy patients (50/67), according to the per protocol analysis. By the intent-to-treat analysis, the figures were 74% vs. 70%. The difference between the two groups was not statistically significant, Dr. Miehlke said.
Seven of 10 patients who failed high-dose dual therapy were cured by crossover to triple therapy.
Eight of 10 patients who failed triple therapy were cured by crossover to high-dose dual therapy.
Posttreatment resistance to amoxicillin or rifabutin was not detected. There were more adverse events reported by patients who were given triple therapy (35%) than by those who received dual therapy (20%). The most common events reported were nausea, diarrhea, headache, and erythema.