UH Physician-Scientists Study Genetic Markers of Resistance in Helicobacter pylori

Innovations in Digestive Health | Winter 2023

University Hospitals Cleveland Medical Center physician-scientists collaborated with colleagues at Case Western Reserve University School of Medicine to conduct the first known study of Helicobacter pylori (H. pylori) antimicrobial susceptibility testing as the standard of care. Findings from their retrospective study were recently published in the American Journal of Gastroenteology (AJG).

Linda Cummings, MD, MS

Named for its helical shape, H. pylori is a gram-negative, microaerophilic, spiral bacterium responsible for infections of the mucoid lining of the stomach. It is estimated that 30 to 40 percent of the U.S. population will develop an H. pylori infection, most in childhood. Diagnostic testing includes blood, breath or stool tests, but many patients require upper endoscopy with biopsy. Treatment involves a combination of antibiotics and acid-reducing medications. Follow-up treatment is needed to confirm that the infection is eradicated. 

“H. pylori is a leading cause of peptic ulcers, gastritis and stomach cancer,” says co-first-author Linda Cummings, MD, MS, a gastroenterologist at UH Cleveland Medical Center and Associate Professor of Medicine at School of Medicine. Leila Hojat, MD, MS, an infectious disease expert at UH Cleveland Medical Center and Assistant Professor at School of Medicine, also co-first-authored the article. 

“Unfortunately, H. pylori is difficult to treat and can require a regimen of up to four medications,” says Dr. Cummings. “As the bacterium is becoming increasingly resistant to antibiotics, researchers have discovered several genetic mutations associated with poor eradication outcomes.” Due to increasing antibiotic resistance, starting patients on empiric treatment for H. pylori can expose them to unnecessary, ineffective antibiotics and lead to future resistance.

Further confounding medical management, H. pylori is extremely challenging to culture. “With many infections, you send a sample to the lab to be cultured for susceptibility against various antibiotics,” says Dr. Cummings. However, she explains that H. pylori requires fastidious growth conditions in lab settings. “Biopsies can be sent for culture but do not always result in growth such that, a few weeks later, we may be no closer to identifying an effective antibiotic.” 

In 2019, pathologists under the leadership of Navid Sadri, MD, PhD, chief of the Division of Genomic and Molecular Pathology at University Hospitals and School of Medicine, published a study of H. pylori mutations associated with treatment failure in the Journal of Clinical Microbiology. The team examined 133 gastric biopsy specimens positive for H. pylori “using a next-generation sequencing (NGS) assay to detect mutations that are known to confer resistance to clarithromycin, levofloxacin and tetracycline.”¹

That work informed the recent “AJG” publication, in which the authors evaluated the impact of routine NGS testing with tailored treatment recommendations on eradication success. The authors note that NGS testing led to the identification of genetic mutations associated with antimicrobial resistance (MAAR) in 55 percent of the samples. Focusing on genetic markers of resistance to generate a recommended treatment regimen was “associated with an 84% rate of eradication success and 4.4 greater odds of eradication relative to unrecommended treatment.”²

University Hospitals is leading the way in providing assay testing as standard of care for patients with H. pylori. While other health systems may need to send samples to an outside laboratory for susceptibility testing, University Hospitals has invested in in-house MAAR testing. “We are not waiting to see whether the patient responds to a first line of empiric treatment. If H. pylori is found during regular pathology review following endoscopy, the sample is automatically tested to check for mutations that predict antibiotic resistance,” says Dr. Cummings. “I don’t know of any other health system currently offering this testing as standard protocol.” 

The field of H. pylori management is rapidly changing. While future study is needed, early results indicate that routine evaluation of MAAR can help providers tailor initial therapy, improve patient outcomes and foster antibiotic stewardship. “As our understanding of mutation-associated resistance in H. pylori continues to grow, some experts are stating that if success with empiric treatment is lower than 90 percent, you should be adding antimicrobial susceptibility testing,” says Dr. Cummings. 

For more information, contact Dr. Cummings at Linda.Cummings@UHhospitals.org. 

1. Behtash G. Nezami, Mehul Jani, David Alouani, Daniel D. Rhoads, and Navid Sadri. Helicobacter pylori Mutations Detected by Next-Generation Sequencing in Formalin-Fixed, Paraffin-Embedded Gastric Biopsy Specimens Are Associated with Treatment Failure. July 2019  Volume 57  Issue 7  e01834-18 https://doi.org/10.1128/JCM.01834-18

2. Cummings, Linda C. MD, MS1,2,*; Hojat, Leila S. MD, MS2,3,*; Nguyen, David C. MD2,4; Stempak, Lisa M. MD5,6; Rhoads, Daniel D. MD7; Sadri, Navid MD, PhD5,6. Tailored Treatment Based on Helicobacter pylori Genetic Markers of Resistance Is Associated With Higher Eradication Success. The American Journal of Gastroenterology 118(2):p 360-363, February 2023. | DOI: 10.14309/ajg.0000000000002085

Contributing Expert: 
Linda Cummings, MD, MS
UH Digestive Health Institute
University Hospitals Cleveland Medical Center 
Associate Professor of Medicine
Case Western Reserve University School of Medicine