Affiliation:
1. Latvian Biomedical Research and Study Centre, Riga, Latvia
2. Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
3. Institute of Clinical and Preventive Medicine, University of Latvia; Faculty of Medicine, University of Latvia, Riga, Latvia
Abstract
Abstract
The spread of extended-spectrum beta-lactamases (ESBLs) in nosocomial and community-acquired enterobacteria is an important challenge for clinicians due to the limited therapeutic options for infections that are caused by these organisms. The epidemiology of these infections is complex and combines the expansion of mobile genetic elements with clonal spread. Insufficient empirical therapy for serious infections caused by these organisms is independently associated with increased mortality. Here, we developed an ESBL coding gene panel, evaluated the abundance and prevalence of ESBLs encoding genes in patients undergoing H. pylori eradication therapy, and summarized the effect of eradication therapy on gut microbiome functional profiles. To assess the repertoire of known beta lactamase (BL) genes, we divided them in clusters according to their evolutionary relation, designed primers for amplification of cluster marker regions and assessed efficiency of this amplification panel on 120 fecal samples acquired from 60 patients undergoing H. pylori eradication therapy. In addition, fecal samples from additional 30 patients were used to validate the detection efficiency of designed ESBL panel. The presence for majority of targeted clusters was confirmed by NGS of amplification products. Metagenomic sequencing revealed that the abundance of ESBL genes within the pool of microorganisms was very low. The global relative abundances of the ESBL-coding gene clusters did not differ significantly across the treatment states. However, at the level of each cluster, classical ESBL producers, such as Klebsiella sp. for blaOXY (p = 0.0076), Acinetobacter sp. for blaADC (p = 0.02297), and others, differed significantly with a tendency to decrease compared to the pre- and post-eradication states. Only 13 clusters were common among all three datasets, suggesting a patient-specific prevalence profile of ESBL-coding genes. The number of AMR genes detected in the post-eradication state was higher than that in the pre-eradication state, which at least partly might be attributed to the therapy. This study demonstrated that the ESBL screening panel was efficient for targeting ESBL-coding gene clusters from bacterial DNA and that minor differences exist in the abundance and prevalence of ESBL-coding gene levels before and after eradication therapy.
Funder
European Regional Development Fund
Publisher
Research Square Platform LLC
Reference91 articles.
1. Prevalence of extended-spectrum beta-lactamase genes in Acinetobacter baumannii strains isolated from nosocomial infections in Tehran, Iran;Abdar MH;GMS Hyg Infect Control,2019
2. Adegoke, A.A., Stenström, T.A., Okoh, A.I., 2017. Stenotrophomonas maltophilia as an Emerging Ubiquitous Pathogen: Looking Beyond Contemporary Antibiotic Therapy. Frontiers in Microbiology .
3. The impact of production of extended-spectrum β-lactamases on the 28-day mortality rate of patients with Proteus mirabilis bacteremia in Korea;Ahn JY;BMC Infect Dis,2017
4. CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database;Alcock BP;Nucleic Acids Res,2020
5. ESBL expression and antibiotic resistance patterns in a hospital in Saudi Arabia: Do healthcare staff have the whole picture?;Aldrazi FA;J Infect Public Health,2019