Over the past decade, Helicobacter pylori strains have reached “alarming levels” of antimicrobial resistance worldwide, investigators reported in the November issue of Gastroenterology.
In a large meta-analysis spanning 2007-2017, H. pylori isolates showed a 15% or higher pooled prevalence of primary and secondary resistance to clarithromycin, metronidazole, and levofloxacin in almost all World Health Organization (WHO) regions. “Local surveillance networks are required to select appropriate eradication regimens for each region,” concluded Alessia Savoldi, MD, of the University of Tübingen (Germany) and her associates.
Typically, the threshold of antimicrobial resistance for choosing empiric regimens is 15%, Dr. Savoldi and her associates noted. Their systematic review and meta-analysis included 178 studies comprising 66,142 isolates from 65 countries. They defined H. pylori infection as a positive histology, serology, stool antigen, urea breath test, or rapid urease test. They excluded studies of fewer than 50 isolates, studies that only reported resistance as a percentage with no denominator, studies that failed to specify time frames or clustered data over more than 3 years, and data reported in guidelines, conference presentations, or letters without formal publication.
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The prevalence of primary clarithromycin resistance exceeded 15% in the WHO European Region (18%; 95% confidence interval, 16%-20%), the Eastern Mediterranean Region (33%), and the Western Pacific Region (34%) and reached 10% in the Americas and the South East Asia region. Furthermore, primary resistance to metronidazole exceeded 15% in all WHO regions, ranging from 56% in the Eastern Mediterranean Region to 23% in the Americas. Resistance to levofloxacin was at least 15% in all WHO regions except the European region (11%).
In most regions, H. pylori also accrued substantially more antimicrobial resistance over time, the investigators said. Clarithromycin resistance rose from 13% during 2006 through 2008 to 21% during 2012 through 2016 (P less than .001). Levofloxacin resistance in the Western Pacific region increased from 12% to 31% during the same two time periods (P less than .001). Several other WHO regions showed less significant trends toward increasing resistance. Multidrug resistance also rose. Resistance to both clarithromycin and metronidazole increased markedly in all WHO areas with available data, reaching 14% in the Eastern Mediterranean and Western Pacific regions and 23% in the European region.
Secondary analyses linked resistance with dramatic increases in the odds of treatment failure. For example, clarithromycin resistance conferred a sevenfold increase in the odds of treatment failure for regimens containing clarithromycin (odds ratio, 7.0; 95% CI, 5.2 to 9.3; P less than .001). Corresponding ORs were 8.2 for levofloxacin resistance, 2.5 for metronidazole resistance, and 9.4 for dual clarithromycin-metronidazole resistance.
The investigators acknowledged several limitations. Of publications in this meta-analysis, 85% represented single-center studies with limited sample sizes, they wrote. Studies often excluded demographic and endoscopic details. Furthermore, only three studies provided prevalence data for the WHO Africa Region and these only provided overall estimates without stratifying by resistance type.
The German Center for Infection Research, Clinical Research Unit, and the WHO Priority List Pathogens project helped fund the work. One coinvestigator disclosed ties to RedHill Biopharma, BioGaia, and Takeda related to novel H. pylori therapies.
SOURCE: Savoldi A et al. Gastroenterology. 2018 Nov. doi: 10.1053/j.gastro.2018.07.007.