Molecular point-of-care testing for lower respiratory tract pathogens improves safe antibiotic de-escalation in patients with pneumonia in the ICU: Results of a randomised controlled trial
Introduction
Lower respiratory tract infections are responsible for a huge burden of disease globally, causing in excess of 3 million deaths in 2019.1 Timely administration of appropriate antimicrobials is a central principal in the care of patients with pneumonia.2,3 Large retrospective datasets have shown associations between increasing time to first dose of antimicrobials and worse outcomes.4 In spite of this, the current gold-standard for microbiological diagnosis remains culture-based methods which typically take around 48–72 h to generate results. Furthermore, conventional culture-based diagnostic tests only identify causative pathogens in 20–40% of patients5,6 with even lower yields following antimicrobial treatment.7 As a result, most critically unwell patients with pneumonia are treated empirically with broad spectrum antimicrobials for prolonged periods. These agents are associated with the development of antimicrobial resistance and antibiotic related side effects, such as Clostridiodies difficile infection. Empirical regimens may also be ineffective against unusual or antibiotic-resistant pathogens, leading to poor patient outcomes.8
Rapid multiplex molecular diagnostic tests have recently been developed which detect a wide variety of pneumonia pathogens in lower respiratory tract samples and take around 1 h to generate results. In diagnostic accuracy studies, these tests have been shown consistently to correlate well with culture-based test results and also to detect pathogens in a greater proportion of patients than conventional testing.9,10 However, to date there have been no published high-quality interventional trials assessing the clinical impact of using these tests. In previous studies we have demonstrated that molecular point-of-care testing (mPOCT) for respiratory viruses including Influenza and SARS-CoV-2, is achievable in patients presenting acutely to hospital, and associated with wide-ranging benefits to patient care including, rapid and appropriate isolation facility use, improved use of Influenza antivirals and reduced length of hospital stay.11, 12, 13 The aim of this trial was to assess the impact of mPOCT using the BioFire Filmarray Pneumonia panel (Biofire diagnostics LLC, Salt Lake City, Utah, US) on antimicrobial use, in critically ill patients with pneumonia.
Section snippets
Study design
We performed a single-centre, pragmatic, parallel group, open-label, randomised, controlled trial in a large UK hospital, between July 2019 and May 2021. All patients were recruited from the General Intensive Care Unit (GICU), Respiratory High Dependency Unit (rHDU) or Neurological Intensive Care Unit (NICU) of Southampton General Hospital (SGH). The hospital is an NHS acute teaching hospital run by University Hospital Southampton NHS Foundation trust, who were the trial sponsor. The study was
Results
Between July 10, 2019, and May 5, 2021, 296 patients were assessed for eligibility in the study and 200 were randomly assigned to either mPOCT (n = 100) or standard clinical care (n = 100). Patient flow through the study is shown in Fig. 1. No patients were withdrawn. One patient was transferred to another hospital before the results of their microbiological testing were available (in the control group), and so did not have data available for the primary endpoint. All patients were analysed in
Discussion
Our study is the first to our knowledge, to report on the clinical impact of molecular POCT for pneumonia pathogens in a critical care environment. It demonstrates that mPOCT led to the identification of a causative pathogen much more rapidly and in a greater proportion of patients than with current standard diagnostic testing. This in turn was associated with more patients receiving antimicrobial treatment directed by a microbiological result, and on average, almost 2 days earlier than with
Data sharing
The data analysed and presented in this study are available from the corresponding author on reasonable request, providing this meets local ethical and research governance criteria.
Funding
This study was funded by the University Hospital Southampton NHS Foundation Trust (UHSFT) with support from Biofire diagnostics and BioMerieux, who provided the pneumonia panel test kits, procalcitonin test kits and the analysers free-of-charge. The laboratory work, nursing costs, and statistical support were supported by the National Institute for Health Research (NIHR) Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre. The funder of the study had no role
Declaration of Competing Interest
TWC has received equipment and consumables free-of-charge from Biofire diagnostics and BioMeriuex to support this work. TWC has received speaker fees, honoraria, travel reimbursement, and equipment and consumables at discount or free of charge for the purposes independent of research, outside of this submitted study, from BioFire diagnostics, BioMerieux and QIAGEN. TWC has received consultancy fees from Cepheid, Synairgen research, Randox laboratories and Cidara therapeutics. He has received
Acknowledgments
We would like to acknowledge and give thanks to all the patients who kindly participated in this study and their families who offered consultee opinions in personally challenging circumstances. We would also like to thank all the clinical staff at University Hospital Southampton who cared for them. We also acknowledge the Department of Health and Social Care Antimicrobial Research Capital Funding Award (reference NIHR200638) for support with laboratory work. We would like to further acknowledge
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