Tay et al. proposed recently a new quadruple therapy after the failure of a first-line therapy for eradicating Helicobacter pylori. They reported an impressive eradication rate of >95%. However, they prescribed this regimen according to preantibiotic sensitivity testing based on bacterial culture. Although this approach seems to achieve a higher eradication rate, it may not be suitable for use in primary care.
Current Maastricht IV guidelines still advise clarithromycin-based 7-day triple therapy in areas of low clarithromycin resistance, although clarithromycin resistance is very high worldwide, ranging from <10% in Northern Europe to 18.9% in Asia and 29.3% in America. However, this does not reflect the current eradication rate worldwide using this therapeutic regimen. In fact, its success rate has remained stable in the Far East as, for example, occurred from 2000 to 2010 in South Korea (86.7% vs. 88.3%, P = 0.06).
On the contrary, in our experience, its effectiveness decreased significantly during the last decade or so. From January 1996 to December 2006, we treated 1497 dyspeptic patients with standard 7-day triple therapy (PPI-amoxycillin-clarithromycin). The overall H. pylori eradication rate was 70.4% (on intention-to-treat analysis). However, looking at the trend during the observation period, we found that it decreased significantly from 90.0% (95% CI: 87.1–93.9) in 1996 to 51.1% (95% CI: 48.1–55.9) in 2006 on intention-to-treat analysis (P = 0.001). It was well tolerated, with adverse events occurring in 7.9% (95% CI: 4.7–10.1) of the overall population, and only 1.4% of the overall population (95% CI: 0.33–3.6) had to discontinue treatment and withdraw from the study.
After multivariate analysis, only smoking habit influenced eradication rates. Several other factors, ranging from adherence to therapy to age at the time of treatment, were assessed, but none were significant (see Table 1). Why this difference between Italy and other countries has occurred remains unclear, but it needs more in-depth analysis.
|Adjusted OR (95% CI)||P|
|Age at the time of diagnosis|
|<45 years||1.03 (0.65–1.91)||0.5|
|Smoking habits||10.03 (4.68–38.98)||0.002|
|Disease at entry|
|Severe gastritis/duodenitis||1.3 (0.8–1.69)||0.4|
|Mild gastritis/duodenitis||1.3 (0.73–1.625||0.4|
|Compliance to the therapy (% of tablets taken)|
In terms of using culture in managing resistant H. pylori infection, performing culture systematically in primary care has some limitations. Culture is not always available on a routine basis, it is expensive and time-consuming, especially when a low bacterial load is present, the sensitivity is not 100%, and therefore the antimicrobial susceptibility cannot be obtained in all cases; and antibiotic susceptibility testing in clinical practice yields useful information only with respect to a few antibiotics. In our experience, levofloxacin-containing sequential therapy can be used as an alternative strategy.
In conclusion, the optimal first-line H. pylori eradication therapy has yet to be discovered. Preantibiotic sensitivity testing should be used with caution, due to several limitations that affect the test yet.