BACKGROUND: Treatment of Helicobacter pylori infection is often empiric; however, current guidelines for management of Helicobacter pylori infection advise against the use of standard triple therapy (clarithromycin, amoxicillin, and proton-pump inhibitor) when clarithromycin resistance exceeds 20%. We developed and tested a new culture-free assay to detect clarithromycin resistance-conferring mutations to determine the prevalence of H. pylori clarithromycin resistance in patients from the United States Pacific Northwest. MATERIALS AND METHODS: Droplet digital PCR (ddPCR) was used to detect the H. pylori 23S rRNA gene, and resistance-conferring mutations, in archived, formalin-fixed, paraffin-embedded (FFPE) gastric tissue and to retrospectively determine the prevalence of clarithromycin-resistant H. pylori among 110 patients at an academic medical center in the Northwest United States between 2012 and 2014. RESULTS: Of 102 patients with the H. pylori 23S rRNA gene detected by the ddPCR assay, 45 (44%) had clarithromycin resistance mutations. Thirty-three of the 45 patients with clarithromycin resistance mutations had a mix of wild-type and resistance alleles. Prevalence of clarithromycin resistance mutations differed among racial groups and was highest among Asians, with mutations detected in 14 (67%) of the 21 patient samples. CONCLUSIONS: The prevalence of clarithromycin resistance detected in this region exceeds 20%, indicating that standard triple therapy should not be the first-line antibiotic treatment for H. pylori infection. Culture-free assays for detecting clarithromycin resistance mutations can be performed on archived tissue samples and will aid in informing tailored treatment for effective H. pylori eradication.
BACKGROUND: Treatment of Helicobacter pylori infection is often empiric; however, current guidelines for management of Helicobacter pylori infection advise against the use of standard triple therapy (clarithromycin, amoxicillin, and proton-pump inhibitor) when clarithromycin resistance exceeds 20%. We developed and tested a new culture-free assay to detect clarithromycin resistance-conferring mutations to determine the prevalence of H. pylori clarithromycin resistance in patients from the United States Pacific Northwest. MATERIALS AND METHODS: Droplet digital PCR (ddPCR) was used to detect the H. pylori 23S rRNA gene, and resistance-conferring mutations, in archived, formalin-fixed, paraffin-embedded (FFPE) gastric tissue and to retrospectively determine the prevalence of clarithromycin-resistant H. pylori among 110 patients at an academic medical center in the Northwest United States between 2012 and 2014. RESULTS: Of 102 patients with the H. pylori 23S rRNA gene detected by the ddPCR assay, 45 (44%) had clarithromycin resistance mutations. Thirty-three of the 45 patients with clarithromycin resistance mutations had a mix of wild-type and resistance alleles. Prevalence of clarithromycin resistance mutations differed among racial groups and was highest among Asians, with mutations detected in 14 (67%) of the 21 patient samples. CONCLUSIONS: The prevalence of clarithromycin resistance detected in this region exceeds 20%, indicating that standard triple therapy should not be the first-line antibiotic treatment for H. pylori infection. Culture-free assays for detecting clarithromycin resistance mutations can be performed on archived tissue samples and will aid in informing tailored treatment for effective H. pylori eradication.
Authors: Peter Malfertheiner; Francis Megraud; Colm A O'Morain; John Atherton; Anthony T R Axon; Franco Bazzoli; Gian Franco Gensini; Javier P Gisbert; David Y Graham; Theodore Rokkas; Emad M El-Omar; Ernst J Kuipers Journal: Gut Date: 2012-05 Impact factor: 23.059
Authors: J Versalovic; M S Osato; K Spakovsky; M P Dore; R Reddy; G G Stone; D Shortridge; R K Flamm; S K Tanaka; D Y Graham Journal: J Antimicrob Chemother Date: 1997-08 Impact factor: 5.790
Authors: C P Dooley; H Cohen; P L Fitzgibbons; M Bauer; M D Appleman; G I Perez-Perez; M J Blaser Journal: N Engl J Med Date: 1989-12-07 Impact factor: 91.245
Authors: David A Baltrus; Manuel R Amieva; Antonello Covacci; Todd M Lowe; D Scott Merrell; Karen M Ottemann; Markus Stein; Nina R Salama; Karen Guillemin Journal: J Bacteriol Date: 2008-10-24 Impact factor: 3.490
Authors: Benjamin Chun-Yu Wong; Shiu Kum Lam; Wai Man Wong; Jian Shun Chen; Ting Ting Zheng; Rui E Feng; Kam Chuen Lai; Wayne Hsing Cheng Hu; Siu Tsan Yuen; Suet Yi Leung; Daniel Yee Tak Fong; Joanna Ho; Chi Kong Ching; Jun Shi Chen Journal: JAMA Date: 2004-01-14 Impact factor: 56.272
Authors: Sarah Talarico; Mahboobeh Safaeian; Paula Gonzalez; Allan Hildesheim; Rolando Herrero; Carolina Porras; Bernal Cortes; Ann Larson; Ferric C Fang; Nina R Salama Journal: Helicobacter Date: 2015-12-15 Impact factor: 5.753
Authors: Benjamin J Hindson; Kevin D Ness; Donald A Masquelier; Phillip Belgrader; Nicholas J Heredia; Anthony J Makarewicz; Isaac J Bright; Michael Y Lucero; Amy L Hiddessen; Tina C Legler; Tyler K Kitano; Michael R Hodel; Jonathan F Petersen; Paul W Wyatt; Erin R Steenblock; Pallavi H Shah; Luc J Bousse; Camille B Troup; Jeffrey C Mellen; Dean K Wittmann; Nicholas G Erndt; Thomas H Cauley; Ryan T Koehler; Austin P So; Simant Dube; Klint A Rose; Luz Montesclaros; Shenglong Wang; David P Stumbo; Shawn P Hodges; Steven Romine; Fred P Milanovich; Helen E White; John F Regan; George A Karlin-Neumann; Christopher M Hindson; Serge Saxonov; Bill W Colston Journal: Anal Chem Date: 2011-10-28 Impact factor: 6.986