Researchers from the University of East Anglia (UK) have investigated a nanopore sequencing device that has the potential to accelerate diagnosis and resistance profiling of infections and explored the capacity of the device against complicated urinary tract infections. By speeding this process up it may enable early de-escalation and refinement of antimicrobial treatment.
Current comprehensive methods of detecting pathogens and resistance genes in specimens suffer from the limitation of speed and cost, impeding their implementation into clinical microbiology.
The Oxford Nanopore Technolgies (UK) MinION device has demonstrated the capacity to characterize bacterial pathogens and predict their antimicrobial resistances in as little as 4 hours from a urine sample, which may enable clinicians to provide tailored treatment, assisting in the battle against antibiotic resistance.
Corresponding author, David Livermore commented: “Identifying specific pathogens and resistance to antibiotics as quickly as possible is the key to reducing the number of patients who are ‘over treated’ with broad-spectrum antibiotics while waiting for results to come through from the micro lab – a process that presently takes a couple of days”.
“This ‘carpet-bombing’ approach -of giving a broad spectrum antibiotic whilst you wait for results -leads to poor antibiotic stewardship. It’s vital that we move beyond it. The way to do so lies in accelerating lab investigation. That way, treatment can be refined earlier. This will benefit the patient, who gets an effective antibiotic, and society, whose diminishing stock of antibiotics is better managed.” Livermore continued.
In the study, bacterial DNA from clinical urines and healthy urines mixed with multiresistant Escherichia coli were sequenced by MinION. The team observed that MinION correctly identified pathogens without culture and detected 51 of 55 resistance genes when results were compared with Illumina sequencing.
However resistance-conferring mutations and allelic variants were not reliably identified.
These findings demonstrate that MinION sequencing has the capacity to identify bacterial pathogens and acquired resistance genes from urine in a short timeframe, suggesting that this method may be utilized to accelerate pathogen identification and enable clinicians to adjust microbial therapy.
Author Justin O’Grady concluded: “Both the type of bacteria and the acquired resistance genes were identified reliably, agreeing with conventional laboratory testing….Challenges remain, though. The approach is currently best suited to difficult cases, but improving hospitals’ antibiotic stewardship requires new diagnostics to be deployed widely.”
“Our method currently requires heavily-infected urine and our rapid analysis can’t yet predict those resistances that arise by mutation – changes to existing genes. But the technology is developing rapidly and we expect to overcome these limitations in the near future.” O’Grady continued.
Sources: Schmidt K, Mwaigwisya S, Crossman LC et al. Identification of bacterial pathogens and antimicrobial resistance directly from clinical urines by nanopore-based metagenomic sequencing. J. Antimicrob. Chemother. doi: 10.1093/jac/dkw397 (2016) (Epub ahead of print);