H. pylori infection: Resistance and recommendations for treatment

Issue: April 2022

ByAshley Franco, PharmD, MS

ByKati Shihadeh, PharmD, BCIDP

Helicobacter pylori is a spiral-shaped gram-negative rod that colonizes the gastric mucosa. H. pylori is mostly acquired in childhood before age 10 years, with more than 50% of people worldwide carrying the organism.

It is the main risk factor for peptic ulcer disease (PUD), gastric ulcers, adenocarcinoma and gastric mucosa-associated lymphoid tumor (MALT). Although most infected individuals are asymptomatic, about 10% to 15% of patients with H. pylori develop PUD during their lifetime and 1% develop gastric cancer over 20 to 40 years. Diagnosis of H. pylori infection is crucial, because treatment can greatly reduce morbidity and mortality. The 2013 American College of Gastroenterology (ACG) recommendation of triple therapy with clarithromycin, metronidazole and a proton pump inhibitor (PPI) as the first-line treatment option has fallen out of favor because growing resistance to this standard therapy has made eradication of H. pylori a challenge.

Diagnosis

In prior literature, indications for H. pylori testing included clinical manifestations of H. pylori infection, such as a history or active PUD or MALT lymphoma. Current literature now suggests testing patients who have conditions outside of gastrointestinal symptoms, such as patients with iron deficiency anemia and idiopathic thrombocytopenia. Testing for confirmatory H. pylori infection includes stool antigen test (SAT), urea breath test (UBT) and serology testing. False-negative results can occur with UBT and SAT, so it is important to discontinue PPIs at least 2 weeks before testing.

Antibiotic resistance

In 2017, WHO classified clarithromycin-resistant H. pylori as a high-priority pathogen. Strains of H. pylori that previously responded to triple therapy with greater than 90% rate of eradication have now become refractory to this standard treatment. Diminishing success of this therapy is due to growing clarithromycin and metronidazole resistance, which occurs in up to 50% of cases. Mechanisms of drug resistance in H. pylori infection include drug efflux pumps or the acquisition of point mutation. Overexpression of hefA pumps have been cited as a mechanism of resistance to metronidazole, whereas point mutations in penicillin-binding proteins and rdxA and gyrA genes represent the primary target of drug resistance in H. pylori. Eradication of H. pylori infection now relies heavily on local antibiotic resistance patterns and patients’ prior antibiotic exposure. Given the burden of disease that H. pylori can cause, diligent antibiotic stewardship is needed to prevent further eradication failure.

Treatment

Any patient with a positive H. pylori test should be treated for an active infection, with the goal to provide succinct treatment with greater than 90% eradication. Given the high resistance rates, the ACG now recommends multiple first-line treatment options with clinical considerations for each treatment regimen (Table 1). Proper treatment includes identifying a patient’s prior antibiotic exposure, reviewing local resistance patterns and analyzing rates of H. pylori eradication with various treatment options.

Given that the eradication rate is so low with the traditional therapy of clarithromycin triple, guidelines recommend choosing this regimen only for patients without prior macrolide exposure and in areas where resistance of clarithromycin is less than 15%. Bismuth quadruple therapy provides similar efficacy as clarithromycin triple therapy, with recommendations to use quadruple therapy where resistance rates are high, patients have prior macrolide exposure and for refractory H. pylori treatment. Non-bismuth quadruple therapy represents another first-line treatment option for patients with H. pylori infection, and it can also be used as salvage therapy in patients with persistent H. pylori infection.

The ACG recommends sequential, hybrid and levofloxacin-containing regimens as alternatives in patients with refractory H. pylori (Table 2). Literature supporting these recommendations in current guidelines find no difference in efficacy compared with clarithromycin-based therapy but suggest these complex regimens offer alternatives in patients refractory to other options. Upon failure of second-line treatment regimens, levofloxacin-containing therapies avoid the use of clarithromycin and are often the regimen selected in salvage therapy. Additionally, guidelines recommend culture and susceptibility testing after two failures of eradication; however, this susceptibility testing is not widely available. Other medication regimens such as high-dose amoxicillin plus a PPI or rifabutin-based treatment options provide salvage options when rates of clarithromycin or fluoroquinolone resistance are high.

The inability to eradicate H. pylori due to rising antibiotic resistance presents health challenges worldwide. Once a modifiable risk factor for the development of gastric cancer or the cause of PUD, H. pylori has now become a globally prevalent, high-risk pathogen. To successfully treat these patients, a multifactorial approach must consider local resistance and optimization of medication regimens that provide ease of adherence.

For more information:
Ashley Franco, PharmD, MS, is a PGY1 pharmacy resident at Denver Health Medical Center.
Kati Shihadeh, PharmD, BCIDP, is a clinical pharmacy specialist in infectious diseases at Denver Health Medical Center. Shihadeh can be reached at katherine.shihadeh@dhha.org.

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Sources/Disclosures

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Disclosures: Franco and Shihadeh report no relevant financial disclosures.

Read more

H. pylori infection: Resistance and recommendations for treatment

Diagnosis

Antibiotic resistance

Treatment

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