Routine Metagenomics Service for Intensive Care Unit Patients with Respiratory Infection

Rationale: Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Objectives: Feasibility, performance and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. Methods: RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory intensive care units (ICU) at Guy’s & St Thomas NHS foundation Trust, London. Measurements and Main Results: During the first 15-weeks RMg provided same-day results for 110 samples (86%) with median turnaround time of 6.7hrs (IQR 6.1-7.5 hrs). RMg was 93% sensitive and 81% 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: This pilot study illustrates the potential of RMg testing to provide benefits for antimicrobial treatment, infection control and public health, when provided in a real-world critical care setting. Multi-centre studies are now required to inform future translation into routine service. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).