Coronavirus Disease 2019 Vaccination Is Associated With Reduced Outpatient Antibiotic Prescribing in Older Adults With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2: A Population-Wide Cohort Study

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Abstract

Background

Antibiotics are frequently prescribed unnecessarily in outpatients with coronavirus disease 2019 (COVID-19). We sought to evaluate factors associated with antibiotic prescribing in outpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods

We performed a population-wide cohort study of outpatients aged ≥66 years with polymerase chain reaction–confirmed SARS-CoV-2 from 1 January 2020 to 31 December 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1 week before (prediagnosis) and 1 week after (postdiagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary-series COVID-19 vaccination, in univariate and multivariable analyses.

Results

We identified 13 529 eligible nursing home residents and 50 885 eligible community-dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3020 (22%) and 6372 (13%), respectively, received at least 1 antibiotic prescription within 1 week of a SARS-CoV-2 positive result. Antibiotic prescribing in nursing home and community residents occurred, respectively, at 15.0 and 10.5 prescriptions per 1000 person-days prediagnosis and 20.9 and 9.8 per 1000 person-days postdiagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted postdiagnosis incidence rate ratios (95% confidence interval) of 0.7 (0.4–1) and 0.3 (0.3–0.4), respectively.

Conclusions

Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis but was reduced in COVID-19–vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19.

Abstract

Outpatient antibiotic use around the time of SARS-CoV-2 diagnosis is common. A completed primary COVID-19 (2-dose) vaccination series is associated with significantly reduced antibiotic use around the time of SARS-CoV-2 diagnosis.

Graphical Abstract

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Most cited references 42

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis

Bradley Langford, Miranda So, Sumit Raybardhan … (2020)

Background Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood. Aims To determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19. Sources We performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection. Content Data were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4–6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6–18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3–9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3–13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%). Implications Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment.

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Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19

Alexandre B Cavalcanti, Fernando Zampieri, Regis Rosa … (2020)

Abstract Background Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. Methods We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. Results A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. Conclusions Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.)

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Author and article information

Contributors

Derek R MacFadden

Colleen Maxwell:

ORCID: https://orcid.org/0000-0002-7988-2899

Dawn Bowdish

Susan Bronskill

James Brooks

Kevin Brown

Lori L Burrows

Anna Clarke

Bradley Langford:

ORCID: https://orcid.org/0000-0001-5467-6776

Elizabeth Leung

Valerie Leung:

ORCID: https://orcid.org/0000-0002-6780-5378

Doug Manuel

Allison McGeer

Sharmistha Mishra

Andrew M Morris

Caroline Nott

Sumit Raybardhan

Mia Sapin

Kevin L Schwartz

Miranda So:

ORCID: https://orcid.org/0000-0002-2765-2063

Jean-Paul R Soucy

Nick Daneman

Journal

Journal ID (nlm-ta): Clin Infect Dis

Journal ID (iso-abbrev): Clin Infect Dis

Journal ID (publisher-id): cid

Title: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

Publisher: Oxford University Press (US )

ISSN (Print): 1058-4838

ISSN (Electronic): 1537-6591

Publication date Collection: 01 August 2023

Publication date (Electronic): 31 March 2023

Publication date PMC-release: 31 March 2023

Volume: 77

Issue: 3

Pages: 362-370

Affiliations

Clinical Epidemiology Program, The Ottawa Hospital Research Institute , Ottawa, Canada

ICES , Toronto, Canada

Division of Infectious Diseases, The Ottawa Hospital , Ottawa, Canada

ICES , Toronto, Canada

Schools of Pharmacy and Public Health Sciences, University of Waterloo , Waterloo, Canada

Faculty of Health Sciences, McMaster University , Hamilton, Canada

ICES , Toronto, Canada

Division of Infectious Diseases, The Ottawa Hospital , Ottawa, Canada

Dalla Lana School of Public Health, University of Toronto , Toronto, Canada

Public Health Ontario , Toronto, Canada

Faculty of Health Sciences, McMaster University , Hamilton, Canada

ICES , Toronto, Canada

Dalla Lana School of Public Health, University of Toronto , Toronto, Canada

Public Health Ontario , Toronto, Canada

Unity Health Toronto , Toronto, Canada

Leslie Dan Faculty of Pharmacy, University of Toronto , Toronto, Canada

Public Health Ontario , Toronto, Canada

Michael Garron Hospital, Toronto East Health Network , Toronto, Canada

ICES , Toronto, Canada

Sinai Health System , Toronto, Canada

ICES , Toronto, Canada

Dalla Lana School of Public Health, University of Toronto , Toronto, Canada

Department of Medicine, University of Toronto , Toronto, Canada

MAP Centre for Urban Health Solutions, St. Michael's Hospital, Unity Health Toronto , Toronto, Canada

Institute of Medical Science, University of Toronto , Toronto, Canada

Sinai Health System , Toronto, Canada

Division of Infectious Diseases, The Ottawa Hospital , Ottawa, Canada

Dalla Lana School of Public Health, University of Toronto , Toronto, Canada

Pharmacy Department, North York General Hospital, Toronto , Canada

School of Epidemiology and Public Health, University of Ottawa , Ottawa, Canada

ICES , Toronto, Canada

Dalla Lana School of Public Health, University of Toronto , Toronto, Canada

Public Health Ontario , Toronto, Canada

Unity Health Toronto , Toronto, Canada

Leslie Dan Faculty of Pharmacy, University of Toronto , Toronto, Canada

Toronto General Hospital Research Institute , Toronto, Canada

Dalla Lana School of Public Health, University of Toronto , Toronto, Canada

ICES , Toronto, Canada

Division of Infectious Diseases, Sunnybrook Health Sciences Centre, University of Toronto , Toronto, Canada

Author notes

Correspondence: D. R. MacFadden, The Ottawa Hospital Research Institute, 1053 Carling Ave, Ottawa, Ontario, Canada, K1Y 4E9 ( dmacfadden@ 123456toh.ca ).

Potential conflicts of interest. D. B. reports grants or contracts from the Public Health Agency of Canada, CIHR, Natural Sciences and Engineering Research Council of Canada, and Weston Family Foundation; occasional honoraria for invited talks; payment for expert testimony and a volunteer role for the government of Canada in 3 lawsuits on vaccine mandates; and support for attending meetings and/or travel when invited to speak at conferences. M. S. reports speaker's honorarium for an educational event from the government of Canada; and a role as Chair of the Canadian Society of Hospital Pharmacists Foundation Education Grant Committee (unpaid role to lead the committee to review submissions for the Education Grant competition). S. R. reports payment or honoraria paid to author from Merck for presentation on the role of antimicrobial stewardship pharmacists and facilitator for talk on hospital-acquired pneumonias, and a role as volunteer Board Director and Corporate Secretary with Momiji Health Care Society for a seniors’ supportive housing facility in Toronto. All other authors report no potential conflicts.

All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Author information

Colleen Maxwell https://orcid.org/0000-0002-7988-2899

Bradley Langford https://orcid.org/0000-0001-5467-6776

Valerie Leung https://orcid.org/0000-0002-6780-5378

Miranda So https://orcid.org/0000-0002-2765-2063

Article

Publisher ID: ciad190

DOI: 10.1093/cid/ciad190

PMC ID: 10425187

PubMed ID: 36999314

SO-VID: edb1669b-3144-4c3a-b916-75aaa831b49b

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

History

Date received : 01 February 2023

Date: 27 March 2023

Date: 12 May 2023

Page count

Pages: 9

Funding

Funded by: Ontario MOH and the MLTC, DOI 10.13039/501100000226;

Funded by: Canadian Institutes of Health Research, DOI 10.13039/501100000024;

Funded by: (CIHR);

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Changes in the Appropriateness of US Outpatient Antibiotic Prescribing After the Coronavirus Disease 2019 Outbreak: An Interrupted Time Series Analysis of 2016–2021 Data
Authors: Kao-Ping Chua, Michael A Fischer, Moshiur Rahman …

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Coronavirus Disease 2019 Vaccination Is Associated With Reduced Outpatient Antibiotic Prescribing in Older Adults With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2: A Population-Wide Cohort Study

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Novel Coronavirus Disease COVID-19

Most cited references 42

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19

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