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

Russell, Clark D; Fairfield, Cameron J; Drake, Thomas M; Turtle, Lance; Seaton, R Andrew; Wootton, Dan G; Sigfrid, Louise; Harrison, Ewen M; Docherty, Annemarie B; de Silva, Thushan I; Egan, Conor; Pius, Riinu; Hardwick, Hayley E; Merson, Laura; Girvan, Michelle; Dunning, Jake; Nguyen-Van-Tam, Jonathan S; Openshaw, Peter J M; Baillie, J Kenneth; Semple, Malcolm G; Ho, Antonia; Baillie, J Kenneth; Semple, Malcolm G; Openshaw, Peter JM; Carson, Gail; Alex, Beatrice; Bach, Benjamin; Barclay, Wendy S; Bogaert, Debby; Chand, Meera; Cooke, Graham S; Docherty, Annemarie B; Dunning, Jake; da Silva Filipe, Ana; Fletcher, Tom; Green, Christopher A; Harrison, Ewen M; Hiscox, Julian A; Ho, Antonia YW; Horby, Peter W; Ijaz, Samreen; Khoo, Say; Klenerman, Paul; Law, Andrew; Lim, Wei Shen; Mentzer, Alexander J; Merson, Laura; Meynert, Alison M; Noursadeghi, Mahdad; Moore, Shona C; Palmarini, Massimo; Paxton, William A; Pollakis, Georgios; Price, Nicholas; Rambaut, Andrew; Robertson, David L; Russell,...

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.

Citation

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., Semple, M. G., …Young, P. (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%2821%2900090-2

• Journal Article Type: Article
• Acceptance Date: Apr 13, 2021
• Online Publication Date: Jun 2, 2021
• Publication Date: 2021-08
• Deposit Date: Jul 8, 2021
• Publicly Available Date: Jul 9, 2021
• Journal: The Lancet Microbe
• Print ISSN: 2666-5247
• Electronic ISSN: 2666-5247
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 2
• Issue: 8
• Pages: e354-e365
• DOI: https://doi.org/10.1016/s2666-5247%2821%2900090-2
• Public URL: https://nottingham-repository.worktribe.com/output/5755939
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2666524721000902?via%3Dihub