1249 National and Regional U.S. Antibiotic Resistance to Helicobacter pylori Identified From a Phase 3 Clinical Trial of Treatment Naïve Patients in the United States

Abstract

INTRODUCTION: Antibiotic resistance to Helicobacter varies by region. A 2001 report of H. pylori clinical trials noted 10.6% clarithromycin and 21.6% metronidazole resistance nationally. Regional clarithromycin resistance varied from 8.3% in the West to 13.0% in the Northeast and metronidazole resistance ranged from 22.1% in the Northeast to 27.5% in the Southeast. A 2015 Houston VAMC study noted resistance of 16.4% to clarithromycin and 20.3% to metronidazole. A recent clinical study found additional concerns for increasing resistance at both national and regional levels for H. pylori infection. METHODS: Isolates collected in a multi-center clinical trial (2017-2018) from de-identified patients were tested for minimal inhibitory concentrations (MICs) by agar dilution using Clinical and Laboratory Standards Institute (CLSI) methods. CLSI and EUCAST (The European Committee on Antimicrobial Susceptibility Testing) interpretive breakpoints were applied. MICs were obtained for amoxicillin, clarithromycin, metronidazole and rifabutin. Analysis provided resistance patterns for both national and regional levels. RESULTS: MICs were reported for 345 of 356 clinical isolates recovered from treatment-naïve patients at 55 centers (20 states) across the US. The regions were broken down as Northeast, Southeast, South, Central, and West. The MIC90 was 0.125 µg/mL for amoxicillin, 8 µg/mL for clarithromycin, 64 µg/mL for metronidazole, and ≤0.008 µg/mL for rifabutin. Across all US sites, resistance rates were: amoxicillin 6.7%; clarithromycin 17.4%; metronidazole 43.7% and rifabutin 0.0%. Regional assessment of amoxicillin, clarithromycin and metronidazole resistance was: Northeast 0.0% (n = 0), 31.6% (n = 6) and 36.8% (n = 7); Southeast: 6.1% (n = 8), 22.0% (n = 29) and 51.5% (n = 68); South 6.5% (n = 5), 11.7% (n = 9) and 45.5% (n = 35); Central 0.0% (n = 0), 44.4% (n = 4) and 22.2% (n = 2); and West 8.3% (n = 9), 11.1% (n = 12) and 35.5% (n = 38), respectively. CONCLUSION/DISCUSSION: Nationally, we found greater resistance rates for clarithromycin (17.4%) and metronidazole (43.7%) compared to previous reports from 2001 and 2015. Regionally, clarithromycin resistance was greater for the Northeast, Southeast and Central areas while metronidazole resistance was greater than previously reported across all regions. Amoxicillin resistance was low (6.7%: 0%-8.3%), and no resistance to rifabutin was reported. These emerging resistance patterns support the use of rifabutin based therapies for H. pylori eradication.