Routine Metagenomics Service for ICU Patients with Respiratory Infection

• Published in: American journal of respiratory and critical care medicine 2024-01, Vol.209 (2), p.164-174
• Main Authors: Charalampous, Themoula, Alcolea-Medina, Adela, Snell, Luke B, Alder, Christopher, Tan, Mark, Williams, Tom G S, Al-Yaakoubi, Noor, Humayun, Gul, Meadows, Christopher I S, Wyncoll, Duncan L A, Paul, Richard, Hemsley, Carolyn J, Jeyaratnam, Dakshika, Newsholme, William, Goldenberg, Simon, Patel, Amita, Tucker, Fearghal, Nebbia, Gaia, Wilks, Mark, Chand, Meera, Cliff, Penelope R, Batra, Rahul, O'Grady, Justin, Barrett, Nicholas A, Edgeworth, Jonathan D
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents; Antimicrobial agents; Diagnostic tests; Disease control; Genetic testing; Genomics; Health care; Humans; Intensive Care Units; London; Medical diagnosis; Original; Pathogens; Pilot Projects; Respiratory diseases; Respiratory Tract Infections - diagnosis; Respiratory Tract Infections - drug therapy; Tuberculosis
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.202305-0901OC

Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London. During the first 15 weeks, RMg provided same-day results for 110 samples (86%), with a median turnaround time of 6.7 hours (interquartile range = 6.1-7.5 h). RMg was 93% sensitive and 81% specific for clinically relevant pathogens compared with routine testing. Forty-eight percent of RMg results informed antimicrobial prescribing changes (22% escalation; 26% deescalation) with escalation based on speciation in 20 out of 24 cases and detection of acquired-resistance genes in 4 out of 24 cases. Fastidious or unexpected organisms were reported in 21 samples, including anaerobes (  = 12), , , cytomegalovirus, and ST1326, which was subsequently isolated from the bedside water outlet. Application to consecutive severe community-acquired LRTI cases identified (two with and three with F/S virulence determinants), ( M1uk clone), subspecies equisimilis (STG62647A), and with multiple treatments and public health impacts. 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. Multicenter studies are now required to inform future translation into routine service.