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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

  • Stephen Poole
    Correspondence
    Corresponding author at: Faculty of Medicine, South Academic Block, Southampton General Hospital, Tremona Road LF100, Mailpoint 801, Southampton SO16 6YD, United Kingdom.
    Affiliations
    NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

    Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
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  • Alex R Tanner
    Affiliations
    Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
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  • Vasanth V Naidu
    Affiliations
    Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
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  • Florina Borca
    Affiliations
    NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

    Clinical Informatics Research Unit, University of Southampton, Southampton, United Kingdom
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  • Hang Phan
    Affiliations
    Clinical Informatics Research Unit, University of Southampton, Southampton, United Kingdom
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  • Kordo Saeed
    Affiliations
    Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

    School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
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  • Michael P W Grocott
    Affiliations
    NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

    School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom

    General Intensive Care Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
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  • Ahilanandan Dushianthan
    Affiliations
    NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

    School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom

    General Intensive Care Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
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  • Helen Moyses
    Affiliations
    NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
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  • Tristan W Clark
    Affiliations
    NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

    Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

    School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom

    NIHR Post-Doctoral Fellowship Programme, United Kingdom
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Published:September 08, 2022DOI:https://doi.org/10.1016/j.jinf.2022.09.003

      Highlights

      • The first randomised trial of rapid syndromic molecular testing in pneumonia.
      • Molecular testing for pneumonia detected more pathogens.
      • Molecular results were generated much more rapidly than culture.
      • More patients had early appropriate antibiotic de-escalation and escalation.
      • There were no major differences in clinical and safety outcomes.

      Summary

      Background

      Effective treatment of pneumonia requires timely administration of appropriate antimicrobials but standard diagnostic tests take around 48 h to generate results. Highly accurate, rapid molecular tests have been developed for identifying organisms in lower respiratory tract samples, however their impact on antibiotic use is unknown. The aim of this study was to assess the impact of syndromic molecular point-of-care testing compared to conventional diagnostic testing, on antibiotic use.

      Methods

      In this pragmatic, randomised controlled trial, we enrolled critically ill adults with pneumonia. Patients were assigned (1:1) to molecular testing of samples at the point-of-care or routine clinical care. The primary outcome was the proportion of patients who received results-directed antimicrobial therapy.

      Results

      200 patients were randomly assigned to point-of-care testing (n = 100) or the control group (n = 100). 85 patients had community acquired pneumonia (42 in the mPOCT group and 43 in the control group), 69 hospital acquired pneumonia (30 in mPOCT and 39 in control) and 46 ventilator associated pneumonia (28 in mPOCT and 18 in control). The median [IQR] time to results was 1.7 [1.6-1.9] hours for point-of-care testing and 66.7 [56.7-88.5] hours for standard diagnostics (difference of -65.0 h, 95%CI -68.0 to -62.0; p < 0.0001). 71 (71%) patients in the point-of-care testing arm had pathogens detected compared to 51 (51%) in the control arm (difference of 20%, 95%CI 7 to 33; p = 0.004). 80 (80%) of patients in the point-of-care group received results-directed therapy, compared with 29 (29%) of 99 in the control group (difference of 51%, 95%CI 39-63; p < 0.0001). Time to results-directed therapy was 2.3 [1.8-7.2] hours in the mPOCT group and 46.1 [23.0-51.5] hours in the control group (difference of -43.8 h, 95% CI -48.9 to -38.6; p < 0.0001). 42 (42%) patients in mPOCT group had antibiotics de-escalated compared with 8 (8%) of 98 in the control group (difference of 34%, 95%CI 23-45; p < 0.0001). Time to de-escalation was 4.8 [2.4-13.0] hours in the mPOCT group compared with 46.5 [26.3-48.6] hours in the control group (difference of -41.4 h, 95%CI -53 to -29.7; p < 0.0001). There was no major difference in antibiotic duration or in clinical or safety outcomes between the two groups.

      Conclusions

      Use of molecular point-of-care testing in patients with pneumonia returned results more rapidly and identified more pathogens than conventional testing. This was associated with improvements in appropriate antimicrobial use and appeared safe.

      Keywords

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