Detecting Hidden Antibiotic Resistance With Real-Time-Genomics

The Threat of Antibiotic Resistance

Antibiotic resistance is one of the most pressing challenges in modern healthcare, threatening to render many of our most potent medicines ineffective. This global health crisis not only compromises patient outcomes but also burdens healthcare systems with increased costs and longer hospital stays. Conventional diagnostic methods rely on culturing and phenotypic testing, which often fail to rapidly and accurately detect resistance, especially for rare or low-abundance mechanisms. The delays in growing cultures and subsequent susceptibility testing can lead to critical delays in administering effective treatment, significantly impacting recovery and survival rates.

Advancing Clinical Diagnostics with Real-Time Genomics

The study showcases major advancements in real-time genomics through nanopore sequencing, providing faster, more detailed analysis of pathogen genomes and resistance profiles than traditional diagnostic tools. The research focused on a severe infection by multi-drug resistant Klebsiella pneumoniae, a common hospital pathogen. Initially treated with Ceftazidime-Avibactam, the patient's condition worsened as the pathogen developed resistance. Traditional diagnostics failed to identify the genetic mechanisms behind this resistance.

Using real-time genomics, the team around first author Ela Sauerborn, PhD student at Helmholtz Munich, discovered complex resistance mechanisms, including a novel plasmid-encoded gene variant. This gene, present in low abundance before treatment, highlights the pathogen's ability to adapt under antibiotic pressure.

Implications for Healthcare

Integrating real-time genomics into clinical practice marks a major shift in managing infectious diseases. Rapid, on-site sequencing enables healthcare providers to quickly tailor treatment strategies to the specific genetic profile of pathogens. This immediate insight into resistance profiles allows clinicians to prescribe the most effective antibiotics, reducing treatment delays and improving patient outcomes while minimizing unnecessary exposure to broad-spectrum antibiotics.

Beyond individual care, real-time genomics-based resistance detection enhances infection control and containment. The rapid turnaround and high resolution of resistance mechanism detection facilitate targeted, immediate containment measures, crucial in high-resistance settings to alter the course of disease outbreaks.

"Our application of nanopore sequencing for hidden antimicrobial resistance detection does not only underscore the technology's potential for rapidly informing clinical management all around the world, but also highlights that it can be more sensitive in detecting rare resistance plasmids than established diagnostics.", says Lara Urban.

_{Source: Discovering the hidden: Advancing antibiotic resistance detection with real-time genomics | Research Communities by Springer Nature}