Routine Metagenomics Service for ICU Patients with Respiratory Infection

Abstract

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 ICUs at Guy's and 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 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 (n = 12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus, and Legionella pneumophila ST1326, which was subsequently isolated from the bedside 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. Multicenter studies are now required to inform future translation into routine service.

Figure 1.

Schematic overview of the study. (A) Overview of the patient cohort and sample set included in the respiratory metagenomics (RMg) pilot service. (B) The metagenomics regimen that was followed on a daily basis when samples were requested for RMg service. Steps outlined include sample collection until reporting results to ICU physicians. (C) Respiratory metagenomic end-to-end clinical pathway. LRT = lower respiratory tract; MV = mechanically ventilated; QC = quality control.

Figure 2.

Patient ICU timelines illustrating the integration of RMg results into antimicrobial treatment and infection control decisions. Hospital-acquired lower respiratory tract infection (LRTI): (A) ICU-acquired L. pneumophila ST1326 pneumonia. Unexpected bacteria prompting antibiotic escalation, infection control, and public health interventions. (B) P. aeruginosa ventilator-associated pneumonia (VAP)–LRTI. New bacterial pathogen in patient with severe COVID-19 pneumonitis prompting antibiotic escalation. (C) ICU-acquired vancomycin-resistant E. faecium. Unexpected antimicrobial resistance (AMR) bacteria with patient and infection control impact. (D) Unexpected disseminated reactivation of herpes simplex virus 2 (HSV-2). Community-acquired LRTI: (E) Influenza with secondary S. pyogenes infection. (F) Influenza with secondary Panton–Valentine leukocidin and methicillin-resistant S. aureus (PVL-MRSA) and S. pyogenes infection. (G) Influenza with secondary PVL and methicillin-sensitive S. aureus (PVL-MSSA) and S. dysgalactiae infection. (H) Influenza with secondary invasive aspergillosis prompting urgent treatment. The details of each case are presented in the online supplement. CRP = C-reactive protein; CFU = colony-forming unit; D = day.

Figure 2.

Patient ICU timelines illustrating the integration of RMg results into antimicrobial treatment and infection control decisions. Hospital-acquired lower respiratory tract infection (LRTI): (A) ICU-acquired L. pneumophila ST1326 pneumonia. Unexpected bacteria prompting antibiotic escalation, infection control, and public health interventions. (B) P. aeruginosa ventilator-associated pneumonia (VAP)–LRTI. New bacterial pathogen in patient with severe COVID-19 pneumonitis prompting antibiotic escalation. (C) ICU-acquired vancomycin-resistant E. faecium. Unexpected antimicrobial resistance (AMR) bacteria with patient and infection control impact. (D) Unexpected disseminated reactivation of herpes simplex virus 2 (HSV-2). Community-acquired LRTI: (E) Influenza with secondary S. pyogenes infection. (F) Influenza with secondary Panton–Valentine leukocidin and methicillin-resistant S. aureus (PVL-MRSA) and S. pyogenes infection. (G) Influenza with secondary PVL and methicillin-sensitive S. aureus (PVL-MSSA) and S. dysgalactiae infection. (H) Influenza with secondary invasive aspergillosis prompting urgent treatment. The details of each case are presented in the online supplement. CRP = C-reactive protein; CFU = colony-forming unit; D = day.