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Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study.
Lancet Microbe. 2021 08; 2(8):e354-e365.LM

Abstract

BACKGROUND

Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19.

METHODS

The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded.

FINDINGS

We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59-84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives.

INTERPRETATION

In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist.

FUNDING

National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London.

Authors+Show Affiliations

University of Edinburgh Centre for Inflammation Research, Edinburgh, UK. Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh, UK.Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK. Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, UK.Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK. Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, UK.Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.Emerging Infections and Zoonoses Unit, National Infection Service, Public Health England, Colindale, London, UK.Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK. UK Department of Health and Social Care, London, UK.National Heart and Lung Institute, Imperial College London, London, UK.Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh, UK.Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK. Department of Respiratory Medicine, Alder Hey Children's Hospital, Liverpool, UK.Medical Research Council-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34100002

Citation

Russell, Clark D., et al. "Co-infections, Secondary Infections, and Antimicrobial Use in Patients Hospitalised With COVID-19 During the First Pandemic Wave From the ISARIC WHO CCP-UK Study: a Multicentre, Prospective Cohort Study." The Lancet. Microbe, vol. 2, no. 8, 2021, pp. e354-e365.
Russell CD, Fairfield CJ, Drake TM, et al. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. Lancet Microbe. 2021;2(8):e354-e365.
Russell, C. D., Fairfield, C. J., Drake, T. M., Turtle, L., Seaton, R. A., Wootton, D. G., Sigfrid, L., Harrison, E. M., Docherty, A. B., de Silva, T. I., Egan, C., Pius, R., Hardwick, H. E., Merson, L., Girvan, M., Dunning, J., Nguyen-Van-Tam, J. S., Openshaw, P. J. M., Baillie, J. K., ... Ho, A. (2021). Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. The Lancet. Microbe, 2(8), e354-e365. https://doi.org/10.1016/S2666-5247(21)00090-2
Russell CD, et al. Co-infections, Secondary Infections, and Antimicrobial Use in Patients Hospitalised With COVID-19 During the First Pandemic Wave From the ISARIC WHO CCP-UK Study: a Multicentre, Prospective Cohort Study. Lancet Microbe. 2021;2(8):e354-e365. PubMed PMID: 34100002.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. AU - Russell,Clark D, AU - Fairfield,Cameron J, AU - Drake,Thomas M, AU - Turtle,Lance, AU - Seaton,R Andrew, AU - Wootton,Dan G, AU - Sigfrid,Louise, AU - Harrison,Ewen M, AU - Docherty,Annemarie B, AU - de Silva,Thushan I, AU - Egan,Conor, AU - Pius,Riinu, AU - Hardwick,Hayley E, AU - Merson,Laura, AU - Girvan,Michelle, AU - Dunning,Jake, AU - Nguyen-Van-Tam,Jonathan S, AU - Openshaw,Peter J M, AU - Baillie,J Kenneth, AU - Semple,Malcolm G, AU - Ho,Antonia, AU - ,, Y1 - 2021/06/02/ PY - 2021/6/9/pubmed PY - 2021/6/9/medline PY - 2021/6/8/entrez SP - e354 EP - e365 JF - The Lancet. Microbe JO - Lancet Microbe VL - 2 IS - 8 N2 - BACKGROUND: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. METHODS: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. FINDINGS: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59-84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. INTERPRETATION: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. FUNDING: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London. SN - 2666-5247 UR - https://www.unboundmedicine.com/medline/citation/34100002/Co_infections_secondary_infections_and_antimicrobial_use_in_patients_hospitalised_with_COVID_19_during_the_first_pandemic_wave_from_the_ISARIC_WHO_CCP_UK_study:_a_multicentre_prospective_cohort_study_ DB - PRIME DP - Unbound Medicine ER -