The resistance of Helicobacter pylori to antibiotics is increasing worldwide, with primary and secondary resistance to clarithromycin, metronidazole, and levofloxacin reaching levels higher than 15%, according to a new meta-analysis by researchers at the German Centre for Infection Research – University of Tübingen, GB Rossi University Hospital, University of Verona, Michael E DeBakey VA Medical Centre and Baylor College of Medicine.
Eradication of H. pylori infection has been proven to be instrumental in reducing the incidence of gastric cancer, but the efficacy of treatment has dramatically declined as a result of growing resistance to antimicrobial regimens.
Because the data on global distribution of resistance and the resulting clinical effects are limited, a systematic review and meta-analysis was conducted to evaluate H. pylori resistance globally and to measure the association between resistance to antimicrobial agents and treatment failure.
A total of 178 studies were included in the analysis. Of this group, 42 (24%) were randomised controlled trials and 136 (76%) were observational studies (118 prospective and 18 retrospective). The cohort included 53,583 patients and 66,142 samples (99.5% endoscopic gastric or duodenal biopsies). In addition, the majority (89%) of the studies included specified the minimum inhibitory concentration values used for defining resistance.
Resistance rates varied by geographic location, but overall, both primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were 15% or greater in all World Health Organization designated regions. Of note, metronidazole resistance proved to be the most prevalent worldwide, with levels between 44% and 65%. The only exception to this pan-increase in prevalence was resistance to primary clarithromycin in the Americas and South East Asia region, where it was 10%, and resistance to primary levofloxacin in the European region (11%).
The investigators write that “the implementation of local and national surveillance system networks and the development of new noninvasive techniques in clinical practice are urgently needed to improve treatment effectiveness and consequently limit the malignant and non-malignant burden of H. pylori chronic infection.”
Abstract
Background & Aims: In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However, there are no clear data on the global distribution of resistance or its clinical effects. We performed a systematic review and meta-analysis to assess the distribution of H pylori resistance to commonly used antibiotics and to measure the association between antibiotic resistance and treatment failure.
Methods: We searched publication databases for studies that assessed rates of H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline. Pooled estimates of primary and secondary resistance and 95% CIs were grouped by WHO region. The association between antibiotic resistance and treatment failure was measured by extracting data on treatment efficacy in patients with resistant and susceptible isolates and pooling odds ratios with 95% CIs.
Results: We identified 178 studies, comprising 66142 isolates from 65 countries. Primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were 15% or more in all WHO regions, except primary clarithromycin resistance in the Americas (10%, 95% CI, 4%–16%) and South-East Asia region (10%; 95% CI, 5%–16%) and primary levofloxacin resistance in the European region (11%; 95% CI, 9%–13%). There was considerable heterogeneity (I2 >75%) among all analyses—this might have resulted from the grouping of resistance rates by country. Increasing antibiotic resistance was observed in most WHO regions. Resistance to clarithromycin was significantly associated with failure of clarithromycin-containing regimens (odds ratio, 6.97; 95% CI, 5.23–9.28; P<.001).
Conclusions: Resistance of H pylori to antibiotics has reached alarming levels worldwide, which as a great effect on efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.
Authors
Alessia Savoldi, Elena Carrara, David Y Graham ,Michela Conti, Evelina Tacconelli
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