Abstract
We evaluated the primary resistance of Helicobacter pylori (H. pylori) to routinely used antibiotics in Cambodia, an unexplored topic in the country, and assessed next-generation sequencing’s (NGS) potential to discover genetic resistance determinants. Fifty-five H. pylori strains were successfully cultured and screened for antibiotic susceptibility using agar dilution. Genotypic analysis was performed using NGS data with a CLC genomic workbench. PlasmidSeeker was used to detect plasmids. The correlation between resistant genotypes and phenotypes was evaluated statistically. Resistances to metronidazole (MTZ), levofloxacin (LVX), clarithromycin (CLR), and amoxicillin (AMX) were 96.4%, 67.3%, 25.5%, and 9.1%, respectively. No resistance to tetracycline (TET) was observed. Multi-drug resistance affected 76.4% of strains. No plasmids were found, but genetic determinants of resistance to CLR, LVX, and AMX were 23S rRNA (A2146G and A2147G), GyrA (N87K and D91Y/N/G), and pbp1 (P473L), respectively. No determinants were genetically linked to MTZ or TET resistance. There was high concordance between resistant genotypes and phenotypes for AMX, LVX, and CLR. We observed high antibiotic resistance rates of CLR, MTZ, and LVX, emphasizing the need for periodic evaluation and alternative therapies in Cambodia. NGS showed high capability for detecting genetic resistance determinants and potential for implementation in local treatment policies.
Highlights
Drug resistance is recognized as one of the greatest public health threats, leading to 700,000 deaths per year worldwide
Despite an increasing worldwide trend in antibiotic resistance, a recent meta-analysis showed that only southeast Asia (10%) and the Americas (10%) appeared to have low CLR resistance rates compared to all World Health Organization (WHO) regions [12]
H. pylori primary resistance rates to CLR, MTZ, and LVX were high in Cambodia, warning that the standard triple therapy as a first-line treatment may no longer be effective in southeast Asia, in Cambodia
Summary
Drug resistance is recognized as one of the greatest public health threats, leading to 700,000 deaths per year worldwide This figure is expected to reach to 300 million people, with a loss of up to US$100 trillion for the global economy by 2050, if not addressed [1]. The issue is of great concern because of the rapid spread of multidrug-resistant strains, some of which may be untreatable with available treatments [2]. In this scenario, Helicobacter pylori (H. pylori) has emerged as an alarming bacterium due to its resistance rate, and it has been noted as one of 16 antibiotic-resistant pathogens that pose the most serious threat to human health, according to World Health Organization (WHO), since 2017 [3,4]. Many consensus conferences for H. pylori treatment (e.g., Toronto [8], Maastricht [9], Asia-Pacific [10], Kyoto [11]) have been held to attempt to deal with threats from the effectiveness of current eradication protocols caused by antibiotic resistance in different regions
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