Abstract:
:The gold standard for clinical diagnosis of bacterial lower respiratory infections (LRIs) is culture, which has poor sensitivity and is too slow to guide early, targeted antimicrobial therapy. Metagenomic sequencing could identify LRI pathogens much faster than culture, but methods are needed to remove the large amount of human DNA present in these samples for this approach to be feasible. We developed a metagenomics method for bacterial LRI diagnosis that features efficient saponin-based host DNA depletion and nanopore sequencing. Our pilot method was tested on 40 samples, then optimized and tested on a further 41 samples. Our optimized method (6 h from sample to result) was 96.6% sensitive and 41.7% specific for pathogen detection compared with culture and we could accurately detect antibiotic resistance genes. After confirmatory quantitative PCR and pathobiont-specific gene analyses, specificity and sensitivity increased to 100%. Nanopore metagenomics can rapidly and accurately characterize bacterial LRIs and might contribute to a reduction in broad-spectrum antibiotic use.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Charalampous T,Kay GL,Richardson H,Aydin A,Baldan R,Jeanes C,Rae D,Grundy S,Turner DJ,Wain J,Leggett RM,Livermore DM,O'Grady Jdoi
10.1038/s41587-019-0156-5subject
Has Abstractpub_date
2019-07-01 00:00:00pages
783-792issue
7eissn
1087-0156issn
1546-1696pii
10.1038/s41587-019-0156-5journal_volume
37pub_type
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