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H. pylori resistance highlights need for guided therapy

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Study findings mirror European data

Antimicrobial-resistant strains of H. pylori are increasing in prevalence in the United States. In the study described here, only half of H. pylori strains were susceptible to commonly used antibiotics and approximately one in three were resistant to at least one antibiotic, according to a single-center study of U.S. veterans. The study assessed 656 gastric biopsies randomly selected from a cohort of 1,559 patients who underwent esophagogastroduodenoscopy at the Houston VA Medical Center between 2009 and 2013. Patients were mostly male and had an average age of 60 years. The researchers cultured tissue samples and used the E test to assess minimum inhibitory concentrations for amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline.

Dr. Nimish Vakil

A total of 135 (20.6%) of the biopsies cultured H. pylori, of which half (65 strains) were susceptible to all five antibiotics tested, 31% were resistant to levofloxacin (95% confidence interval, 23%-39%), 20% were resistant to metronidazole (95% CI, 13%-27%), 16% were resistant to clarithromycin (95% CI, 10%-23%), 0.8% were resistant to tetracycline (95% CI, 0%-2%), and none were resistant to amoxicillin, said the researchers.

The study mirrors findings in Europe where similar rates of resistance have been reported. European studies have also shown that levofloxacin resistance rises rapidly when it becomes widely used in the community, The study described here is not population based and consists mostly of male subjects and therefore may not be generalizable to the rest to the rest of the United States. As culture and antimicrobial sensitivity testing is not available to most gastroenterologists, the initial treatment chosen should reflect resistance data in the community. Given the rising rates of resistance, it is important that eradication be confirmed 4 weeks or more after eradication therapy ends using a stool antigen test or a breath test. Clinicians should be prepared to re-treat patients if necessary.

Dr. Nimish Vakil, AGAF, is clinical professor of medicine at the University of Wisconsin School of Medicine and Public Health in Madison. He has no conflicts of interest.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

References

Only half of Helicobacter pylori strains were pansusceptible, and almost one in three was resistant to at least one antibiotic, according to a single-center study of U.S. veterans published in Clinical Gastroenterology and Hepatology.

The analysis is the first published report of H. pylori resistance in more than a decade, said Dr. Seiji Shiota at the Michael E. DeBakey Veterans Affairs Medical Center and the Baylor College of Medicine, Houston, and his associates. “Clarithromycin, metronidazole, and levofloxacin resistances were all high among untreated patients, suggesting that they all should be avoided as components of empiric triple therapy [consisting of a] proton pump inhibitor, amoxicillin, plus a third antibiotic,” said the researchers. “The four-drug concomitant therapy and bismuth quadruple therapy, or antibiotic susceptibility–guided therapy, are likely be the best strategies locally and are recommended for previously untreated patients with H. pylori infection.”

Helicobacter pylori © NDDIC.NIH.gov

Helicobacter pylori

The study assessed 656 gastric biopsies randomly selected from a cohort of 1,559 patients who underwent esophagogastroduodenoscopy at the Houston VA Medical Center between 2009 and 2013. About 90% of patients were male, and patients ranged in age from 40 to 79 years old, with an average age of 60 years. The researchers cultured tissue samples and used the E test to assess minimum inhibitory concentrations for amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline. (Clin Gastroenterol Hepatol. 2015 Feb 11. pii: S1542-3565(15)00122-6).

A total of 135 (20.6%) of the biopsies cultured H. pylori, of which half (65 strains) were susceptible to all five antibiotics tested, 31% were resistant to levofloxacin (95% confidence interval, 23%-39%), 20% were resistant to metronidazole (95% CI, 13%-27%), 16% were resistant to clarithromycin (95% CI, 10%-23%), 0.8% were resistant to tetracycline (95% CI, 0%-2%), and none were resistant to amoxicillin, said the researchers. The extent of levofloxacin resistance was a “new and concerning finding” that was linked in the multivariable analysis with past fluoroquinolone treatment, reflecting the rising use of fluoroquinolones in community practice, they said. “Levofloxacin has been recommended as a rescue drug to eradicate H. pylori in patients who fail first-line therapy,” they added. “Locally, it would seem to be a poor choice on the basis of the high resistance rate (31.9%), which is higher than the 10% limit suggested as a cutoff for use of fluoroquinolone-containing triple therapy for H. pylori.”

Clarithromycin resistance also rose during the study period, probably because of the rising use of macrolides in respiratory and otorhinolaryngology, the investigators noted. Patients who had been treated before for helicobacteriosis were significantly more likely to have clarithromycin-resistant H. pylori infections even after accounting for demographic factors, smoking status, gastroesophageal reflux disease, and past use of macrolides and fluoroquinolones, they said. Based on that result, patients with a history of prior helicobacteriosis should not receive clarithromycin as part of triple therapy, they emphasized.

Resistance to metronidazole also remained high, but only 1.8% of isolates were resistant to both metronidazole and clarithromycin, making combination therapy with a proton pump inhibitor, clarithromycin, metronidazole, and amoxicillin “an excellent choice as an empiric therapy,” added Dr. Shiota and his associates. Furthermore, the study might have overestimated the rate of metronidazole resistance because the E test yielded significantly higher minimum inhibitory concentration values than did agar dilution, they noted. The study cohort also was demographically dissimilar to that of the United States and might have reflected selection bias, because patients with a history of helicobacteriosis would be more likely to be referred for endoscopy, they said.

The National Institutes of Health and the Veterans Affairs Health Services Research & Development Center for Innovations in Quality, Effectiveness, and Safety supported the study. The researchers reported having no conflicts of interest.

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