Implications of the paradigm shift in management of Helicobacter pylori infections

Abstract

The recent availability of susceptibility testing for Helicobacter pylori infections in the United Sates has resulted in paradigm shifts in the diagnosis, therapy, and follow-up of H. pylori infections. Here, we reviewed the English literature concerning changes in H. pylori diagnosis and therapy with an emphasis on the last 3 years. We focus on the new methods that offer rapid and convenient susceptibility testing using either invasive (endoscopic) or noninvasive (stool) methods of obtaining test material. We also discuss the implications of this availability on therapy and follow-up after therapy. The approach to therapy was categorized into four groups: (1) therapies that can be used empirically, (2) therapies that should be restricted to those that are susceptibility-based, (3) potentially effective therapies that have yet to be optimized for local use, and (4), therapies that contain unneeded antibiotics that should not be prescribed. The most convenient and efficient method of susceptibility testing is by using reflexive stool testing in which if the sample is positive, it is automatically also used for determination of susceptibility. Reflexive testing can also be done via reflexive ordering (e.g., for all positive urea breath tests). The post therapy test-of-cure has emerged as a critical component of therapy as it not only provides feedback regarding treatment success but when combined with susceptibility testing also provide evidence regarding the cause of failure (e.g., poor adherence versus emergence of resistance during therapy. Susceptibility testing has made even the most current H. pylori guidelines for diagnosis and therapy generally obsolete. Clarithromycin, metronidazole, and levofloxacin triple therapies should only be administered as susceptibility-based therapy. Regimens containing unneeded antibiotics should not be given. We provide recommendations regarding the details and indications for all current therapies.

Keywords: Helicobacter pylori; heteroresistance; molecular stool testing; optimization; paradigm shift; susceptibility testing; test-of-cure; treatment; treatment failure; treatment guidelines.

Figure 1.

An illustration of the current and now superseded approach to diagnosis and empiric therapy of Helicobacter pylori for patients with and without alarm features.

Figure 2.

An illustration of the use of next generation sequencing for Helicobacter pylori susceptibility using stool, fresh or formalin fixed biopsies, or bacteria from culture plates. Results include amoxicillin, metronidazole, clarithromycin, rifabutin, tetracycline, and levofloxacin.

Figure 3.

Illustration of the steps in reflexive stool testing in which positive samples are automatically sent for next generation sequencing to provide noninvasive susceptibility testing.

Figure 4.

Flow diagram of a stepwise approach to Helicobacter pylori therapy that starts with empiric therapy using a proven locally highly effective regimen. If not, one goes immediately to susceptibility-based therapy.

Figure 5.

Illustration of the importance of the post treatment test-of-cure as feedback to provide the clinician with updated information regarding the local effectiveness of locally optimized therapies. Source: From Graham’s study, with permission.

Figure 6.

Schematic of the entire course of therapy starting with either empiric or susceptibility-based therapy through one treatment failure.

Figure 7.

An algorithm emphasizing the information obtainable from always utilizing the post treatment test-of-cure to both provide information regarding effectiveness of the therapy used and also to provide information regarding the likely cause of treatment failure.