Routine respiratory metagenomics service for intensive care unit patients

Background: Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into clinical practice. Methods: Feasibility, performance and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service for patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory intensive care units (ICU) at Guys & St Thomas NHS foundation Trust, London. Results: RMg was performed on 128 samples from 87 patients during the first 15-weeks providing same-day results for 110 samples (86%) with median turnaround time of 6.7hrs (IQR 6.1-7.5 hrs). RMg was 92% sensitive and 82% specific for clinically-relevant pathogens compared with routine testing. 48% of RMg results informed antimicrobial prescribing changes (22% escalation; 26% de-escalation) with escalation based on speciation in 20/24 cases and detection of acquired-resistance genes in 4/24 cases. Fastidious or unexpected organisms were reported in 21 samples including anaerobes (n=12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus and Legionella pneumophila ST1326, which was subsequently isolated from the bed-side water outlet. Application to consecutive severe community-acquired LRTI cases identified Staphylococcus aureus (two with SCCmec and three with luk F/S virulence determinants), Streptococcus pyogenes (emm1-M1uk clone), S. dysgalactiae subspecies equisimilis (STG62647A) and Aspergillus fumigatus with multiple treatments and public-health impacts. Conclusions: RMg provides frequent diverse benefits for treatment, infection control and public health. The combination of rapid comprehensive results, alongside revealing and characterising a hidden burden of infections makes the case for expediting routine service implementation