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Next-Gen Sequencing for Investigation of Genetic Antimicrobial Resistance Mechanisms

Research aims at demonstrating diagnostic value of next-generation sequencing for antimicrobial susceptibility testing and translation into clinical practice

OpGen, Inc.

OpGen, Inc. (Gaithersburg, MD, USA) is a precision medicine company harnessing the power of molecular diagnostics and bioinformatics to help combat infectious disease. Along with subsidiaries, Curetis GmbH and Ares Genetics GmbH, the company is developing and commercializing molecular microbiology solutions helping to guide clinicians with more rapid and actionable information about life threatening infections to improve patient outcomes, and decrease the spread of infections caused by multidrug-resistant microorganisms, or MDROs. OpGen’s product portfolio includes Unyvero, Acuitas AMR Gene Panel and Acuitas® Lighthouse, and the ARES Technology Platform including ARESdb, using NGS technology and AI-powered bioinformatics solutions for antibiotic response prediction.

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Published:Sep 23, 2020
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VIENNA, AUSTRIA and GAITHERSBURG, MD — September 16, 2020 (GLOBE NEWSWIRE) — OpGen, Inc. (Nasdaq: OPGN, “OpGen”), announced today that scientists at its subsidiary Ares Genetics GmbH (Vienna, Austria; “Ares Genetics”), in collaboration with researchers from the Johns Hopkins University School of Medicine, have published a peer-reviewed study on modifiable risk factors for the emergence of ceftolozane-tazobactam resistance in P. aeruginosa in the journal Clinical Infectious Diseases.

P. aeruginosa is listed by the World Health Organization as critical priority pathogen. To overcome antimicrobial resistance, ceftolozane-tazobactam has been introduced as a novel β-lactam-β-lactamase inhibitor combination agent and received initial U.S. FDA approval in 2014. While pre-clinical investigations indicated ceftolozane-tazobactam activity against approximately 85%-95 percent of US and Canadian carbapenem-non-susceptible P. aeruginosa isolates, soon after the clinical introduction of ceftolozane-tazobactam, reports of resistance during therapy emerged.

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The study published in Clinical Infectious Diseases sought to understand mechanisms of resistance leading to ceftolozane-tazobactam resistance, the frequency of cross-resistance between ceftolozane-tazobactam and other novel beta-lactam beta-lactamase inhibitor combinations and identify modifiable risk factors that may slow or prevent the acquisition of ceftolozane-tazobactam resistance. Findings demonstrate the potential of  next-generation sequencing (NGS) to investigate mechanisms of resistance by analyzing whole-genome sequencing data from P. aeruginosa isolates that developed resistance under treatment with ceftolozane-tazobactam. Mutations identified in ceftolozane-tazobactam resistant isolates involved, amongst others, AmpC, a known binding site for ceftolozane, PBP3, the target of ceftolozane, and DNA polymerase. The researchers propose extending ceftolozane-tazobactam infusions as a potential protective measure against acquired mutational resistance.

The present study is the result of an ongoing collaboration between Ares Genetics and the Johns Hopkins University School of Medicine, with the goal of investigating the diagnostic potential of NGS for antimicrobial susceptibility testing. Earlier this year, Dr. Patricia Simner of Johns Hopkins Medicine and Ares Genetics presented results from a study assessing the potential of long-read sequencing to predict antimicrobial susceptibility results at the online ASM Microbe 2020 meeting.

Dr. Andreas Posch, CEO Ares Genetics and co-author of both studies, commented, “While we have already shown that NGS allows for CLIA-compliant identification of bacterial pathogens and antimicrobial resistance markers as well as accurate prediction of phenotypic resistance in previous publications, the present studies further underline the diagnostic value of NGS as well as the need for rapid antimicrobial resistance testing and improving antibiotic treatment regiments. I am particularly excited about our joint work on using long-read sequencing technology for phenotype prediction as this technology could potentially allow for molecular antibiotic susceptibility testing directly from native patient samples in just a few hours.”

- This press release was originally published on the OpGen website