Background Culture-based microbiological investigation of hospital-acquired or ventilator-associated pneumonia (HAP or VAP) is insensitive, with aetiological agents often unidentified. This can lead to excess antimicrobial treatment of patients with susceptible pathogens, while those with resistant bacteria are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship.
Methods Surplus routine lower respiratory tract samples were collected from intensive care unit patients about to receive new or changed antibiotics for hospital-onset lower respiratory tract infections at 15 UK hospitals. Testing was performed using the BioFire FilmArray Pneumonia Panel (bioMérieux) and Unyvero Pneumonia Panel (Curetis). Concordance analysis compared machine and routine microbiology results, while Bayesian latent class (BLC) analysis estimated the sensitivity and specificity of each test, incorporating information from both PCR panels and routine microbiology.
Findings In 652 eligible samples; PCR identified pathogens in considerably more samples compared with routine microbiology: 60.4% and 74.2% for Unyvero and FilmArray respectively vs 44.2% by routine microbiology. PCR tests also detected more pathogens per sample than routine microbiology. For common HAP/VAP pathogens, FilmArray had sensitivity of 91.7%–100.0% and specificity of 87.5%–99.5%; Unyvero had sensitivity of 50.0%–100.0%%, and specificity of 89.4%–99.0%. BLC analysis indicated that, compared with PCR, routine microbiology had low sensitivity, ranging from 27.0% to 69.4%.
Interpretation Conventional and BLC analysis demonstrated that both platforms performed similarly and were considerably more sensitive than routine microbiology, detecting potential pathogens in patient samples reported as culture negative. The increased sensitivity of detection realised by PCR offers potential for improved antimicrobial prescribing.
- bacterial Infection
- critical care
- respiratory infection
Data availability statement
The dataset for this study is available on request from Norwich Clinical Trials Unit.
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Collaborators INHALE WP1 Study Group: Eleanor Tudtud, BUPA Cromwell Hospital; Luke Moore, Nabeela Mughal and Suveer Singh, Chelsea and Westminster Hospital NHS Foundation Trust; Alistair Roy, City Hospitals Sunderland; Julian Sonksen, Dudley Group NHS Foundation Trust; Nigel Klein and Mark J. Peters, Great Ormond Street Hospital and UCL Great Ormond St Institute of Child Health NIHR Biomedical Research Centre; Meera Chand and Jonathan Edgeworth, Guy’s and St Thomas’ NHS Foundation Trust; Michael Karlikowski, James Paget University Hospitals NHS Foundation Trust; Christopher Parry and Ingeborg D. Welters, Liverpool University Hospitals NHS Foundation Trust; Ben Morton, Liverpool University Hospitals NHS Foundation Trust and Liverpool School of Tropical Medicine; Tim Leary, Parveez Moondi, Catherine Tremlett and Helen Williams, Norfolk and Norwich University Hospitals NHS Foundation Trust; Jeronimo Cuesta, North Middlesex Hospital; Mark Blunt, Queen Elizabeth Hospital Kings Lynn NHS Trust; Damien Mack and Daniel Martin, Royal Free Hospital; David Brealey, University College London Hospital NHS Trust and UCLH NIHR Biomedical Research Centre; Robert Horne and Laura Shallcross, University College London; David Turner, University of East Anglia; Nehal Patel, University Hospitals of North Midlands.
Contributors VIE, VG, DML and JO'G conceived the study and obtained funding. JB, JH and A-MS contributed to study design. VIE and JH obtained study approvals. AC built the study database. AA, RB, DRO, HR, CR and BON-I managed the machine-based testing, generating the data for analysis. HR, DRO, AA and RB performed the supplementary laboratory analyses. VIE and JO'G supervised the laboratory work. CR, HR, AA, DRO and VIE performed data checks and queries. JB and FR wrote the statistical analysis plan and designed the BLC analysis, FR performed the analyses. VIE, VG, DML and JO'G interpreted the data and conceived the scoring system for machine evaluation. VIE wrote the manuscript with assistance from RB and DML. All authors reviewed the manuscript and approved the final version. VIE, FR and RB had full access to the data and could check their validity. VIE accepts full responsibility for the work and the conduct of the study and controlled the decision to publish.
Funding This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Reference Number: RP-PG-0514–20018).The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. The funder had no role in the study design, nor in the collection, analysis, and interpretation of data or in the writing of the report. The funder appointed an independent research Programme Steering Committee (PSC) to provide quality assurance and oversight. The corresponding author had full access to all study data and had final responsibility for the decision to submit for publication.
Competing interests DML: Advisory Boards or ad-hoc consultancy Accelerate, Allecra, Antabio, Centauri, Entasis, GSK, Meiji, Menarini, Mutabilis, Nordic, ParaPharm, Pfizer, QPEX, Roche, Shionogi, Summit, T.A.Z., VenatoRx, Wockhardt, Zambon, Paid lectures– Astellas, bioMérieux, Beckman Coulter, Cardiome, Cepheid, Hikma, Merck/MSD, Menarini, Nordic, Pfizer and Shionogi. Relevant shareholdings or options-Dechra, GSK, Merck, Perkin Elmer, Pfizer, T.A.Z, amounting to <10% of portfolio value. He also has nominated holdings in Avacta, Byotrol, Destiny, Diaceutics, Evgen, Faron, Fusion Antibodies, Genedrive, Hardide, Renalytics, Scancell and Synairgen (all with research/products pertinent to medical and diagnostic innovation) through Enterprise Investment Schemes but has no authority to trade these shares directly. VG: Advisory boards or ad-hoc consultancy Gilead, Shionogi, bioMérieux, MSD, Vidya Diagnostics. VIE: Speaking honoraria, consultancy fees and in-kind contributions from several diagnostic companies including Curetis GmbH, bioMérieux and Oxford Nanopore. JO'G: has received speaking honoraria, consultancy fees, in-kind contributions or research funding from Oxford Nanopore, Simcere, Becton-Dickinson and Heraeus Medical.
Provenance and peer review Not commissioned; externally peer reviewed.