Transitioning of Helicobacter pylori Therapy from Trial and Error to Antimicrobial Stewardship

Abstract

Helicobacter pylori is the only major infection for which antimicrobial therapy is not designed using the principles of antimicrobial stewardship. Traditionally, antimicrobial therapy is a susceptibility-based therapy, achieves high cure rates, and includes surveillance programs to regularly provide updated data regarding resistance, outcomes, and treatment guidelines. Current H. pylori therapies identified by trial-and-error, and treatment recommendations and guidelines are based on comparisons among regimens that rarely take into account the prevalence or effect of resistance. The majority of patients currently treated achieve suboptimal results. A paradigm shift is required to abandon current approaches and embrace antimicrobial stewardship, and therefore reliably achieve high cure rates; develop, propagate, and update best practice guidelines; and provide surveillance of local or regional susceptibility/resistance patterns. These also require timely updates to clinicians regarding the current status of resistance, antimicrobial effectiveness, and ways to prevent antimicrobial misuse to extend the useful life of currently available antibiotics. Here, we discuss the differences among current approaches to H. pylori therapy and antimicrobial stewardship and identify what is required to achieve the transition. Conceptually, the differences are significant, and the transition will likely need to be both abrupt and complete. Recommendations for therapy during the transition period are given.

Keywords: Helicobacter pylori; amoxicillin; antibiotics; antimicrobial stewardship; clarithromycin; ethical trials; fluoroquinolones; metronidazole; proton pump inhibitors; therapy.

Figure 1

Intention to treat cure rates and standard deviations reported from the clinical trials published for studies designed to obtain FDA approval for triple therapy with PPI, clarithromycin, and amoxicillin, in the United States. From [4] with permission.

Figure 2

Helicobacter pylori treatment nomogram illustrating the duration-related difference in cure rate with 7- and 14-day clarithromycin triple therapy and the effect of clarithromycin resistance on the outcome. As shown, 15% clarithromycin resistance results in a decline in the population cure rate to approximately 85% with 14-day therapy and to approximately 75% with 7-day therapy. It also shows the lack of utility of consensus conference recommendations to use 15% resistance as a yes-no guide to therapy.