Medical Inspection – Health Blog

Whether omeprazole was given once or twice daily in combi­nation with clarithromycin and metronidazole, this one- week treatment regimen achieved 80% ITT, 85% APT and 86% to 87% PP Hpylori eradication. Due to small sample size, statistically significant differences may have been missed. However, because the results were exactly the same in both study arms, it is unlikely that clinically significant differences were missed. These one-week results are similar to those of our previously reported two-week omeprazole twice daily results.

While mild side effects were frequent and seen in approx­imately two-thirds of the patients, there was only one treat­ment discontinuation (1%) due to metronidazole-induced excessive perspiring. Overall, 94% of the patients took all their medications. Three patients took only half their dose of metronidazole by error. This problem arose because the pa­tients were prescribed two 250 mg tablets twice daily; the 250 mg tablet is much less expensive than the 500 mg dose and is automatically dispensed according to formulary by the pharmacy. This error resulted in two of the three patients continuing to be H pylori positive; thus, patients should be instructed carefully to take all their medications.

In this community setting, the effects of antibiotic resis­tance were not assessed because culture was not available. In an American study, metronidazole resistance did not predict treatment failure. Our centre participated in the large, multicentre randomized controlled MACH 1 trial, and all 12 of our patients treated with omeprazole, clarithro­mycin, metronidazole (OCM) triple therapy had H pylori eradicated. Although antibiotic resistance was not assessed, the 100% success rate suggests that H pylori metronidazole resistance may not necessarily predict treatment failure. Two recently published Canadian studies have shown that base­line H pylori metronidazole resistance is low at 11% to 12%. These numbers are lower than the 18% to 38% re­ported as abstracts, and may reflect an evolution in the methods and definitions used to define metronidazole re­sistance rather than a change in actual resistance patterns.

In contrast, recent evidence from the MACH 2 study sug­gests that metronidazole resistance only slightly reduces the efficacy of the OCM triple therapy from 95% to 76%. Importantly, this study also showed that the addition of omeprazole, ie, potent acid suppression, partially helped to overcome metronidazole resistance. Thus, there may be some rationale for favouring the greater acid suppression of omeprazole twice daily versus the once daily dose in clinical practice. In the MACH 2 study, omeprazole was given twice daily and the dosage of metronidazole was 400 mg bid – slightly lower than the 500 mg bid used in this study. This may be relevant because there may be a dose response to greater efficacy against resistant H pylori strains with higher doses of metronidazole.

Clarithromycin resistance was not assessed in this study; however, Canadian studies report that baseline clarithro- mycin resistance is less than 3% and as yet proba­bly plays little role in affecting eradication efficacy.

In this community setting, biopsy-based methods are the only methods readily available to assess H pylori status.

C-urea breath tests are now commercially available, but patients appear to be unwilling to to pay for them. Also, the ¹⁴C-urea breath test is available at a teaching centre 45 km away, but the patients are reluctant to travel out of town.

A potential limitation of this study is that histology was the only method used to define eradication. However, taking two biopsies from both the antrum and the body of the stom­ach, as was done in the present study, compared with biopsying the antrum alone, is known to improve diagnostic yield. In a study assessing diagnostic tests to define H pylori eradication after treatment, taking four histological biopsies as done in this study had high sensitivity (96.6%) and specificity (100%) compared with a gold standard of a true positive by a rigorous combination of immunohisto- chemistry, culture, polymerase chain reaction and C urea breath test. Furthermore, the Geimsa stain as used in this study “may be the preferred technique for confirming H pylori infection, due to its accuracy, low cost and technical ease of preparation”. While no single stain is a perfect gold standard, histology as performed in this study is thought to be a practical and adequate method to define H pylori eradication. In some centres, a rapid urease test of biopsy samples may also be done to confirm H pylori eradication.