Exclusion of bacterial co-infection in COVID-19 using baseline inflammatory markers and their response to antibiotics

Mason, Claire; Kanitkar, Tanmay; Richardson, Charlotte; Lanzman, Marisa; Stone, Zak; Mahungu, Tabitha; Mack, Damien; Wey, Emmanuel; Lamb, Lucy; Balakrishnan, Indran; Pollara, Gabriele

doi:10.1093/jac/dkaa563

Cited by 42 publications

(36 citation statements)

References 33 publications

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“…The absence of an elevated white cell count at baseline and antimicrobial-associated C-reactive protein reduction can exclude co-infection in around 50% of patients with COVID-19. 20 Procalcitonin might be an additional decision-making adjunct, using a threshold of 0·25 ng/mL or less to identify patients with a reduced likelihood of bacterial infection. 21 Regular review of drug charts with discontinuation of antimicrobials if co-infection is deemed unlikely, supported by negative microbiological investigations, are also key to minimise unnecessary antimicrobial exposure.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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...

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Bacterial co-infections in COVID-19 are infrequent, creating a need to minimize excessive antibiotic prescribing and selection for resistance. WCC and CRP have limited discriminatory capacity, 1 and PCT has been increasingly used to provide more diagnostic certainty, with several studies using low PCT values, which support the exclusion of bacterial co-infections, to safely reduce antibiotic prescribing. 7 , 11–13 Our findings reveal that low PCT values, especially <0.5 ng/mL, can be predicted from low levels of routinely measured CRP, avoiding the associated costs of PCT testing in over one-third of patients.…”

Section: Discussionmentioning

confidence: 99%

“…The hyperinflammatory state in severe COVID-19 disease resembles but is rarely complicated by bacterial co-infections, 1 , 2 hindering antimicrobial stewardship efforts that seek to minimize unnecessary antibiotic prescribing. Cross-sectional radiological changes lack specificity, microbiological investigations lack sensitivity, and culture-independent biomarkers such as C-reactive protein (CRP) and white cell count (WCC) only partially exclude co-infections, 1 , 3 and procalcitonin (PCT) may provide additional diagnostic discrimination. 4 In non-COVID-19 settings, elevated PCT is associated with bacterial than viral infections, 5 and low PCT values (<0.5 ng/mL) can support cessation of antibiotics.…”

Section: Introductionmentioning

confidence: 99%

C-reactive protein-guided use of procalcitonin in COVID-19

Houghton

Moore

Williams

et al. 2021

JAC-Antimicrobial Resistance

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Background A low procalcitonin (PCT) concentration facilitates exclusion of bacterial co-infections in COVID-19, but high costs associated with PCT measurements preclude universal adoption. Changes in inflammatory markers, including C-reactive protein (CRP), can be concordant, and predicting low PCT concentrations may avoid costs of redundant tests and support more cost-effective deployment of this diagnostic biomarker. Objectives To explore whether, in COVID-19, low PCT values could be predicted by the presence of low CRP concentrations. Methods Unselected cohort of 224 COVID-19 patients admitted to hospital that underwent daily PCT and CRP measurements as standard care. Both 0.25 ng/mL and 0.5 ng/mL were used as cut-offs for positive PCT test results. Geometric mean was used to define high and low CRP values at each timepoint assessed. Results Admission PCT was <0.25 ng/mL in 160/224 (71.4%), 0.25–0.5 ng/mL in 27 (12.0%) and >0.5 ng/mL in 37 (16.5%). Elevated PCT was associated with increased risk of death (P = 0.0004) and was more commonly associated with microbiological evidence of bacterial co-infection (P < 0.0001). For high CRP values, significant heterogeneity in PCT measurements was observed, with maximal positive predictive value of 50% even for a PCT cut-off of 0.25 ng/mL. In contrast, low CRP was strongly predictive of low PCT concentrations, particularly <0.5 ng/mL, with a negative predictive value of 97.6% at time of hospital admission and 100% 48 hours into hospital stay. Conclusions CRP-guided PCT testing algorithms can reduce unnecessary PCT measurement and costs, supporting antimicrobial stewardship strategies in COVID-19.

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“…Even with low rates of positive bacterial coinfection, without a method to distinguish at-risk patient groups, cautious over-prescribing of antibacterials will continue [ 5 ]. Work to date has highlighted the potential for traditional biomarkers (e.g., C-reactive protein (CRP) and neutrophils) to exclude bacterial co-infection but most of this work was completed before the introduction of dexamethasone in standard care [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Procalcitonin to Guide Antibacterial Prescribing in Patients Hospitalised with COVID-19

2021

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Antibacterial prescribing in patients presenting with COVID-19 remains discordant to rates of bacterial co-infection. Implementing diagnostic tests to exclude bacterial infection may aid reduction in antibacterial prescribing. (1) Method: A retrospective observational analysis was undertaken of all hospitalised patients with COVID-19 across a single-site NHS acute Trust (London, UK) from 1 December 2020 to 28 February 2021. Electronic patient records were used to identify patients, clinical data, and outcomes. Procalcitonin (PCT) serum assays, where available on admission, were analysed against electronic prescribing records for antibacterial prescribing to determine relationships with a negative PCT result (<25 mg/L) and antibacterial course length. (2) Results: Antibacterial agents were initiated on admission in 310/624 (49.7%) of patients presenting with COVID-19. A total of 33/74 (44.5%) patients with a negative PCT on admission had their treatment stopped within 24 h. A total of 6/49 (12.2%) patients were started on antibacterials, but a positive PCT saw their treatment stopped. Microbiologically confirmed bacterial infection was low (19/594; 3.2%) and no correlation was seen between PCT and culture positivity (p = 1). Lower mortality (15.6% vs. 31.4%; p = 0.049), length of hospital stay (7.9 days vs. 10.1 days; p = 0.044), and intensive care unit (ICU) admission (13.9% vs. 40.8%; p = 0.001) was noted among patients with low PCT. (3) Conclusions: This retrospective analysis of community acquired COVID-19 patients demonstrates the potential role of PCT in excluding bacterial co-infection. A negative PCT on admission correlates with shorter antimicrobial courses, early cessation of therapy, and predicts lower frequency of ICU admission. Low PCT may support decision making in cessation of antibacterials at the 48–72 h review.

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Exclusion of bacterial co-infection in COVID-19 using baseline inflammatory markers and their response to antibiotics

Cited by 42 publications

References 33 publications

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

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

C-reactive protein-guided use of procalcitonin in COVID-19

Procalcitonin to Guide Antibacterial Prescribing in Patients Hospitalised with COVID-19

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