Nanopore sequencing demonstrates identification of antibiotic-resistant pathogens hidden to traditional methods in new study

Rapid and accurate antibiotic resistance profiling with Oxford Nanopore sequencing demonstrates potential for clinical impact.

A new study published in Nature Communications has demonstrated the ability of real-time nanopore sequencing in identifying the antibiotic resistance of pathogens hidden to standard traditional methods, such as MALDI-TOF MS and VITEK 2, showcasing the potential for rapid nanopore sequencing to characterise drug resistant infections in a hospital setting.

Rosemary Sinclair Dokos, SVP for Product and Programme Management at Oxford Nanopore Technologies, said that the study “highlights the potential of real-time genomic technology to significantly enhance our understanding of antibiotic resistance,” adding, “by providing rapid and detailed insights, this technology has the potential to support timely and informed decision-making, and could lead to better outcomes in infectious disease and improved public health strategies."

The research, led by Ela Sauerborn under the supervision of Dr. Lara Urban and her team at Helmholtz Center Munich, was conducted in a research hospital and demonstrates how real-time genomics can offer rapid, precise insights that traditional methods might miss.

Antibiotic resistance is recognised as one of the top ten global health threats, increasing mortality and morbidity due to delayed or inappropriate therapy. The study emphasises the urgent need for rapid and accurate pathogen identification to combat this issue effectively. In terms of speed, the study showcases equivalence of nanopore sequencing to traditional methods. However, the biggest differentiator is that, within a similar timeframe to VITEK 2 and MALDI-TOF MS, real-time genomics uncovered plasmid-encoded resistance genes that these methods missed - identification of which is crucial for timely and appropriate therapy.

This point was demonstrated in a case study by Dr. Urban’s team that focused on a multi-drug resistant Klebsiella pneumoniae infection. This strain of bacteria has developed antibiotic resistance in some cases, and a decision was made to change antibiotic treatment from Meropenem to Ceftazidime-Avibactam (CAZ-AVI), the latter being recommended given the strain’s susceptibility to CAZ-AVI. However, traditional methods were unable to detect that the Klebsiella pneumoniae infection had developed resistance to CAZ-AVI itself.

In a recreation of the case study, Dr. Urban’s team used nanopore sequencing to accurately identify the presence of KPC-14 resistance genes, predicting antibiotic resistance accurately as opposed to established clinical diagnostics. This demonstrated that nanopore sequencing could have unveiled the CAZ-AVI resistance that other methods failed to detect, thereby influencing the therapeutic approach, such as the early administration of alternative antibiotics or combination therapy and potentially leading to positive outcomes. Further, this approach is cost-effective and suitable for global application in every clinical microbiology setting, while the accessibility of the platform enables low- and middle-income settings to adopt real-time genomic tools, particularly where there are barriers to the use of standard diagnostic machinery.

Dr. Lara Urban commented, "The fast, adaptive, and in situ nature of antibiotic resistance profiling by nanopore sequencing would have surpassed current clinical practice in accurately informing clinical management."

The study was conducted in collaboration with esteemed institutions, including the Technical University of Munich, Helmholtz Zentrum München, and the European Molecular Biology Laboratory European Bioinformatics Institute. This partnership underscores the global effort to advance genomic research and combat antibiotic resistance through innovative technology.

For more details, please visit the full study published in Nature Communications.

First author Ela Sauerborn will be discussing this research at the Nanopore Community Meeting 2024: Boston this September. To join her and hear the latest scientific breakthroughs register here now.