Early Empiric Antibiotic Use in Patients Hospitalized With COVID-19: A Retrospective Cohort Study

On behalf of the N3C Consortium; J. Christian Widere; Claire Leilani Davis; Johanna Jean Loomba; Taison D. Bell; Kyle B. Enfield; Andrew Julio Barros; Benjamin Amor; Mark M. Bissell; Katie Rebecca Bradwell; Andrew T. Girvin; Amin Manna; Nabeel Qureshi; Christopher G. Chute; Emily R. Pfaff; Davera Gabriel; Stephanie S. Hong; Kristin Kostka; Harold P. Lehmann; Richard A. Moffitt; Michele Morris; Matvey B. Palchuk; Xiaohan Tanner Zhang; Richard L. Zhu; Christopher P. Austin; Kenneth R. Gersing; Samuel Bozzette; Mariam Deacy; Nicole Garbarini; Michael G. Kurilla; Sam G. Michael; Joni L. Rutter; Meredith Temple-O'Connor; Melissa A. Haendel; Tellen D. Bennett; Christopher G. Chute; David A. Eichmann; Justin Guinney; Warren A. Kibbe; Hongfang Liu; Philip R.O. Payne; Emily R. Pfaff; Peter N. Robinson; Joel H. Saltz; Heidi Spratt; Justin Starren; Christine Suver; Adam B. Wilcox; Andrew E. Williams; Chunlei Wu; Emily R. Pfaff; Benjamin Amor; Mark M. Bissell; Marshall Clark; Andrew T. Girvin; Stephanie S. Hong; Kristin Kostka; Adam M. Lee; Robert T. Miller; Michele Morris; Matvey B. Palchuk; Kellie M. Walters; Melissa A. Haendel; Christopher G. Chute; Kenneth R. Gersing; Anita Walden; Anita Walden; Yooree Chae; Connor Cook; Alexandra Dest; Racquel R. Dietz; Thomas Dillon; Patricia A. Francis; Rafael Fuentes; Alexis Graves; Julie A. McMurry; Andrew J. Neumann; Shawn T. O'Neil; Usman Sheikh; Andréa M. Volz; Elizabeth Zampino; Mary Morrison Saltz; Christine Suver; Christopher G. Chute; Melissa A. Haendel; Julie A. McMurry; Andréa M. Volz; Anita Walden; Carolyn Bramante; Jeremy Richard Harper; Wenndy Hernandez; Farrukh M. Koraishy; Federico Mariona; Amit Saha; Satyanarayana Vedula

doi:10.1097/CCM.0000000000005901

Early Empiric Antibiotic Use in Patients Hospitalized With COVID-19: A Retrospective Cohort Study

On behalf of the N3C Consortium, J. Christian Widere, Claire Leilani Davis, Johanna Jean Loomba, Taison D. Bell, Kyle B. Enfield, Andrew Julio Barros, Benjamin Amor, Mark M. Bissell, Katie Rebecca Bradwell, Andrew T. Girvin, Amin Manna, Nabeel Qureshi, Christopher G. Chute, Emily R. Pfaff, Davera Gabriel, Stephanie S. Hong, Kristin Kostka, Harold P. Lehmann, Richard A. MoffittMichele Morris, Matvey B. Palchuk, Xiaohan Tanner Zhang, Richard L. Zhu, Christopher P. Austin, Kenneth R. Gersing, Samuel Bozzette, Mariam Deacy, Nicole Garbarini, Michael G. Kurilla, Sam G. Michael, Joni L. Rutter, Meredith Temple-O'Connor, Melissa A. Haendel, Tellen D. Bennett, Christopher G. Chute, David A. Eichmann, Justin Guinney, Warren A. Kibbe, Hongfang Liu, Philip R.O. Payne, Emily R. Pfaff, Peter N. Robinson, Joel H. Saltz, Heidi Spratt, Justin Starren, Christine Suver, Adam B. Wilcox, Andrew E. Williams, Chunlei Wu, Emily R. Pfaff, Benjamin Amor, Mark M. Bissell, Marshall Clark, Andrew T. Girvin, Stephanie S. Hong, Kristin Kostka, Adam M. Lee, Robert T. Miller, Michele Morris, Matvey B. Palchuk, Kellie M. Walters, Melissa A. Haendel, Christopher G. Chute, Kenneth R. Gersing, Anita Walden, Anita Walden, Yooree Chae, Connor Cook, Alexandra Dest, Racquel R. Dietz, Thomas Dillon, Patricia A. Francis, Rafael Fuentes, Alexis Graves, Julie A. McMurry, Andrew J. Neumann, Shawn T. O'Neil, Usman Sheikh, Andréa M. Volz, Elizabeth Zampino, Mary Morrison Saltz, Christine Suver, Christopher G. Chute, Melissa A. Haendel, Julie A. McMurry, Andréa M. Volz, Anita Walden, Carolyn Bramante, Jeremy Richard Harper, Wenndy Hernandez, Farrukh M. Koraishy, Federico Mariona, Amit Saha, Satyanarayana Vedula

Research output: Contribution to journal › Article › peer-review

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Abstract

OBJECTIVE: To investigate temporal trends and outcomes associated with early antibiotic prescribing in patients hospitalized with COVID-19. DESIGN: Retrospective propensity-matched cohort study using the National COVID Cohort Collaborative (N3C) database. SETTING: Sixty-six health systems throughout the United States that were contributing to the N3C database. Centers that had fewer than 500 admissions in their dataset were excluded. PATIENTS: Patients hospitalized with COVID-19 were included. Patients were defined to have early antibiotic use if they received at least 3 calendar days of intravenous antibiotics within the first 5 days of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 322,867 qualifying first hospitalizations, 43,089 patients received early empiric antibiotics. Antibiotic use declined across all centers in the data collection period, from March 2020 (23%) to June 2022 (9.6%). Average rates of early empiric antibiotic use (EEAU) also varied significantly between centers (deviance explained 7.33% vs 20.0%, p < 0.001). Antibiotic use decreased slightly by day 2 of hospitalization and was significantly reduced by day 5. Mechanical ventilation before day 2 (odds ratio [OR] 3.57; 95% CI, 3.42-3.72), extracorporeal membrane oxygenation before day 2 (OR 2.14; 95% CI, 1.75-2.61), and early vasopressor use (OR 1.85; 95% CI, 1.78-1.93) but not region of residence was associated with EEAU. After propensity matching, EEAU was associated with an increased risk for in-hospital mortality (OR 1.27; 95% CI, 1.23-1.33), prolonged mechanical ventilation (OR 1.65; 95% CI, 1.50-1.82), late broad-spectrum antibiotic exposure (OR 3.24; 95% CI, 2.99-3.52), and late Clostridium difficile infection (OR 1.60; 95% CI, 1.37-1.87). CONCLUSIONS: Although treatment of COVID-19 patients with empiric antibiotics has declined during the pandemic, the frequency of use remains high. There is significant inter-center variation in antibiotic prescribing practices and evidence of potential harm. Our findings are hypothesis-generating and future work should prospectively compare outcomes and adverse events.

Original language	English
Pages (from-to)	1168-1176
Number of pages	9
Journal	Critical care medicine
Volume	51
Issue number	9
DOIs	https://doi.org/10.1097/CCM.0000000000005901
State	Published - Sep 1 2023

Keywords

COVID-19
antimicrobial prescribing
bacterial coinfection
drug resistance
pneumonia

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On behalf of the N3C Consortium, Widere, J. C., Davis, C. L., Loomba, J. J., Bell, T. D., Enfield, K. B., Barros, A. J., Amor, B., Bissell, M. M., Bradwell, K. R., Girvin, A. T., Manna, A., Qureshi, N., Chute, C. G., Pfaff, E. R., Gabriel, D., Hong, S. S., Kostka, K., Lehmann, H. P., ... Vedula, S. (2023). Early Empiric Antibiotic Use in Patients Hospitalized With COVID-19: A Retrospective Cohort Study. Critical care medicine, 51(9), 1168-1176. https://doi.org/10.1097/CCM.0000000000005901

@article{eee3033127ea4de39f9ab7dbf3ca0212,

title = "Early Empiric Antibiotic Use in Patients Hospitalized With COVID-19: A Retrospective Cohort Study",

abstract = "OBJECTIVE: To investigate temporal trends and outcomes associated with early antibiotic prescribing in patients hospitalized with COVID-19. DESIGN: Retrospective propensity-matched cohort study using the National COVID Cohort Collaborative (N3C) database. SETTING: Sixty-six health systems throughout the United States that were contributing to the N3C database. Centers that had fewer than 500 admissions in their dataset were excluded. PATIENTS: Patients hospitalized with COVID-19 were included. Patients were defined to have early antibiotic use if they received at least 3 calendar days of intravenous antibiotics within the first 5 days of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 322,867 qualifying first hospitalizations, 43,089 patients received early empiric antibiotics. Antibiotic use declined across all centers in the data collection period, from March 2020 (23%) to June 2022 (9.6%). Average rates of early empiric antibiotic use (EEAU) also varied significantly between centers (deviance explained 7.33% vs 20.0%, p < 0.001). Antibiotic use decreased slightly by day 2 of hospitalization and was significantly reduced by day 5. Mechanical ventilation before day 2 (odds ratio [OR] 3.57; 95% CI, 3.42-3.72), extracorporeal membrane oxygenation before day 2 (OR 2.14; 95% CI, 1.75-2.61), and early vasopressor use (OR 1.85; 95% CI, 1.78-1.93) but not region of residence was associated with EEAU. After propensity matching, EEAU was associated with an increased risk for in-hospital mortality (OR 1.27; 95% CI, 1.23-1.33), prolonged mechanical ventilation (OR 1.65; 95% CI, 1.50-1.82), late broad-spectrum antibiotic exposure (OR 3.24; 95% CI, 2.99-3.52), and late Clostridium difficile infection (OR 1.60; 95% CI, 1.37-1.87). CONCLUSIONS: Although treatment of COVID-19 patients with empiric antibiotics has declined during the pandemic, the frequency of use remains high. There is significant inter-center variation in antibiotic prescribing practices and evidence of potential harm. Our findings are hypothesis-generating and future work should prospectively compare outcomes and adverse events.",

keywords = "COVID-19, antimicrobial prescribing, bacterial coinfection, drug resistance, pneumonia",

author = "{On behalf of the N3C Consortium} and Widere, {J. Christian} and Davis, {Claire Leilani} and Loomba, {Johanna Jean} and Bell, {Taison D.} and Enfield, {Kyle B.} and Barros, {Andrew Julio} and Benjamin Amor and Bissell, {Mark M.} and Bradwell, {Katie Rebecca} and Girvin, {Andrew T.} and Amin Manna and Nabeel Qureshi and Chute, {Christopher G.} and Pfaff, {Emily R.} and Davera Gabriel and Hong, {Stephanie S.} and Kristin Kostka and Lehmann, {Harold P.} and Moffitt, {Richard A.} and Michele Morris and Palchuk, {Matvey B.} and Zhang, {Xiaohan Tanner} and Zhu, {Richard L.} and Austin, {Christopher P.} and Gersing, {Kenneth R.} and Samuel Bozzette and Mariam Deacy and Nicole Garbarini and Kurilla, {Michael G.} and Michael, {Sam G.} and Rutter, {Joni L.} and Meredith Temple-O'Connor and Haendel, {Melissa A.} and Bennett, {Tellen D.} and Chute, {Christopher G.} and Eichmann, {David A.} and Justin Guinney and Kibbe, {Warren A.} and Hongfang Liu and Payne, {Philip R.O.} and Pfaff, {Emily R.} and Robinson, {Peter N.} and Saltz, {Joel H.} and Heidi Spratt and Justin Starren and Christine Suver and Wilcox, {Adam B.} and Williams, {Andrew E.} and Chunlei Wu and Pfaff, {Emily R.} and Benjamin Amor and Bissell, {Mark M.} and Marshall Clark and Girvin, {Andrew T.} and Hong, {Stephanie S.} and Kristin Kostka and Lee, {Adam M.} and Miller, {Robert T.} and Michele Morris and Palchuk, {Matvey B.} and Walters, {Kellie M.} and Haendel, {Melissa A.} and Chute, {Christopher G.} and Gersing, {Kenneth R.} and Anita Walden and Anita Walden and Yooree Chae and Connor Cook and Alexandra Dest and Dietz, {Racquel R.} and Thomas Dillon and Francis, {Patricia A.} and Rafael Fuentes and Alexis Graves and McMurry, {Julie A.} and Neumann, {Andrew J.} and O'Neil, {Shawn T.} and Usman Sheikh and Volz, {Andr{\'e}a M.} and Elizabeth Zampino and Saltz, {Mary Morrison} and Christine Suver and Chute, {Christopher G.} and Haendel, {Melissa A.} and McMurry, {Julie A.} and Volz, {Andr{\'e}a M.} and Anita Walden and Carolyn Bramante and Harper, {Jeremy Richard} and Wenndy Hernandez and Koraishy, {Farrukh M.} and Federico Mariona and Amit Saha and Satyanarayana Vedula",

year = "2023",

month = sep,

day = "1",

doi = "10.1097/CCM.0000000000005901",

language = "English",

volume = "51",

pages = "1168--1176",

journal = "Critical care medicine",

issn = "0090-3493",

number = "9",

}

On behalf of the N3C Consortium, Widere, JC, Davis, CL, Loomba, JJ, Bell, TD, Enfield, KB, Barros, AJ, Amor, B, Bissell, MM, Bradwell, KR, Girvin, AT, Manna, A, Qureshi, N, Chute, CG, Pfaff, ER, Gabriel, D, Hong, SS, Kostka, K, Lehmann, HP, Moffitt, RA, Morris, M, Palchuk, MB, Zhang, XT, Zhu, RL, Austin, CP, Gersing, KR, Bozzette, S, Deacy, M, Garbarini, N, Kurilla, MG, Michael, SG, Rutter, JL, Temple-O'Connor, M, Haendel, MA, Bennett, TD, Chute, CG, Eichmann, DA, Guinney, J, Kibbe, WA, Liu, H, Payne, PRO, Pfaff, ER, Robinson, PN, Saltz, JH, Spratt, H, Starren, J, Suver, C, Wilcox, AB, Williams, AE, Wu, C, Pfaff, ER, Amor, B, Bissell, MM, Clark, M, Girvin, AT, Hong, SS, Kostka, K, Lee, AM, Miller, RT, Morris, M, Palchuk, MB, Walters, KM, Haendel, MA, Chute, CG, Gersing, KR, Walden, A, Walden, A, Chae, Y, Cook, C, Dest, A, Dietz, RR, Dillon, T, Francis, PA, Fuentes, R, Graves, A, McMurry, JA, Neumann, AJ, O'Neil, ST, Sheikh, U, Volz, AM, Zampino, E, Saltz, MM, Suver, C, Chute, CG, Haendel, MA, McMurry, JA, Volz, AM, Walden, A, Bramante, C, Harper, JR, Hernandez, W, Koraishy, FM, Mariona, F, Saha, A & Vedula, S 2023, 'Early Empiric Antibiotic Use in Patients Hospitalized With COVID-19: A Retrospective Cohort Study', Critical care medicine, vol. 51, no. 9, pp. 1168-1176. https://doi.org/10.1097/CCM.0000000000005901

TY - JOUR

T1 - Early Empiric Antibiotic Use in Patients Hospitalized With COVID-19

T2 - A Retrospective Cohort Study

AU - On behalf of the N3C Consortium

AU - Widere, J. Christian

AU - Davis, Claire Leilani

AU - Loomba, Johanna Jean

AU - Bell, Taison D.

AU - Enfield, Kyle B.

AU - Barros, Andrew Julio

AU - Amor, Benjamin

AU - Bissell, Mark M.

AU - Bradwell, Katie Rebecca

AU - Girvin, Andrew T.

AU - Manna, Amin

AU - Qureshi, Nabeel

AU - Chute, Christopher G.

AU - Pfaff, Emily R.

AU - Gabriel, Davera

AU - Hong, Stephanie S.

AU - Kostka, Kristin

AU - Lehmann, Harold P.

AU - Moffitt, Richard A.

AU - Morris, Michele

AU - Palchuk, Matvey B.

AU - Zhang, Xiaohan Tanner

AU - Zhu, Richard L.

AU - Austin, Christopher P.

AU - Gersing, Kenneth R.

AU - Bozzette, Samuel

AU - Deacy, Mariam

AU - Garbarini, Nicole

AU - Kurilla, Michael G.

AU - Michael, Sam G.

AU - Rutter, Joni L.

AU - Temple-O'Connor, Meredith

AU - Haendel, Melissa A.

AU - Bennett, Tellen D.

AU - Chute, Christopher G.

AU - Eichmann, David A.

AU - Guinney, Justin

AU - Kibbe, Warren A.

AU - Liu, Hongfang

AU - Payne, Philip R.O.

AU - Pfaff, Emily R.

AU - Robinson, Peter N.

AU - Saltz, Joel H.

AU - Spratt, Heidi

AU - Starren, Justin

AU - Suver, Christine

AU - Wilcox, Adam B.

AU - Williams, Andrew E.

AU - Wu, Chunlei

AU - Pfaff, Emily R.

AU - Amor, Benjamin

AU - Bissell, Mark M.

AU - Clark, Marshall

AU - Girvin, Andrew T.

AU - Hong, Stephanie S.

AU - Kostka, Kristin

AU - Lee, Adam M.

AU - Miller, Robert T.

AU - Morris, Michele

AU - Palchuk, Matvey B.

AU - Walters, Kellie M.

AU - Haendel, Melissa A.

AU - Chute, Christopher G.

AU - Gersing, Kenneth R.

AU - Walden, Anita

AU - Chae, Yooree

AU - Cook, Connor

AU - Dest, Alexandra

AU - Dietz, Racquel R.

AU - Dillon, Thomas

AU - Francis, Patricia A.

AU - Fuentes, Rafael

AU - Graves, Alexis

AU - McMurry, Julie A.

AU - Neumann, Andrew J.

AU - O'Neil, Shawn T.

AU - Sheikh, Usman

AU - Volz, Andréa M.

AU - Zampino, Elizabeth

AU - Saltz, Mary Morrison

AU - Suver, Christine

AU - Chute, Christopher G.

AU - Haendel, Melissa A.

AU - McMurry, Julie A.

AU - Volz, Andréa M.

AU - Walden, Anita

AU - Bramante, Carolyn

AU - Harper, Jeremy Richard

AU - Hernandez, Wenndy

AU - Koraishy, Farrukh M.

AU - Mariona, Federico

AU - Saha, Amit

AU - Vedula, Satyanarayana

PY - 2023/9/1

Y1 - 2023/9/1

N2 - OBJECTIVE: To investigate temporal trends and outcomes associated with early antibiotic prescribing in patients hospitalized with COVID-19. DESIGN: Retrospective propensity-matched cohort study using the National COVID Cohort Collaborative (N3C) database. SETTING: Sixty-six health systems throughout the United States that were contributing to the N3C database. Centers that had fewer than 500 admissions in their dataset were excluded. PATIENTS: Patients hospitalized with COVID-19 were included. Patients were defined to have early antibiotic use if they received at least 3 calendar days of intravenous antibiotics within the first 5 days of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 322,867 qualifying first hospitalizations, 43,089 patients received early empiric antibiotics. Antibiotic use declined across all centers in the data collection period, from March 2020 (23%) to June 2022 (9.6%). Average rates of early empiric antibiotic use (EEAU) also varied significantly between centers (deviance explained 7.33% vs 20.0%, p < 0.001). Antibiotic use decreased slightly by day 2 of hospitalization and was significantly reduced by day 5. Mechanical ventilation before day 2 (odds ratio [OR] 3.57; 95% CI, 3.42-3.72), extracorporeal membrane oxygenation before day 2 (OR 2.14; 95% CI, 1.75-2.61), and early vasopressor use (OR 1.85; 95% CI, 1.78-1.93) but not region of residence was associated with EEAU. After propensity matching, EEAU was associated with an increased risk for in-hospital mortality (OR 1.27; 95% CI, 1.23-1.33), prolonged mechanical ventilation (OR 1.65; 95% CI, 1.50-1.82), late broad-spectrum antibiotic exposure (OR 3.24; 95% CI, 2.99-3.52), and late Clostridium difficile infection (OR 1.60; 95% CI, 1.37-1.87). CONCLUSIONS: Although treatment of COVID-19 patients with empiric antibiotics has declined during the pandemic, the frequency of use remains high. There is significant inter-center variation in antibiotic prescribing practices and evidence of potential harm. Our findings are hypothesis-generating and future work should prospectively compare outcomes and adverse events.

AB - OBJECTIVE: To investigate temporal trends and outcomes associated with early antibiotic prescribing in patients hospitalized with COVID-19. DESIGN: Retrospective propensity-matched cohort study using the National COVID Cohort Collaborative (N3C) database. SETTING: Sixty-six health systems throughout the United States that were contributing to the N3C database. Centers that had fewer than 500 admissions in their dataset were excluded. PATIENTS: Patients hospitalized with COVID-19 were included. Patients were defined to have early antibiotic use if they received at least 3 calendar days of intravenous antibiotics within the first 5 days of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 322,867 qualifying first hospitalizations, 43,089 patients received early empiric antibiotics. Antibiotic use declined across all centers in the data collection period, from March 2020 (23%) to June 2022 (9.6%). Average rates of early empiric antibiotic use (EEAU) also varied significantly between centers (deviance explained 7.33% vs 20.0%, p < 0.001). Antibiotic use decreased slightly by day 2 of hospitalization and was significantly reduced by day 5. Mechanical ventilation before day 2 (odds ratio [OR] 3.57; 95% CI, 3.42-3.72), extracorporeal membrane oxygenation before day 2 (OR 2.14; 95% CI, 1.75-2.61), and early vasopressor use (OR 1.85; 95% CI, 1.78-1.93) but not region of residence was associated with EEAU. After propensity matching, EEAU was associated with an increased risk for in-hospital mortality (OR 1.27; 95% CI, 1.23-1.33), prolonged mechanical ventilation (OR 1.65; 95% CI, 1.50-1.82), late broad-spectrum antibiotic exposure (OR 3.24; 95% CI, 2.99-3.52), and late Clostridium difficile infection (OR 1.60; 95% CI, 1.37-1.87). CONCLUSIONS: Although treatment of COVID-19 patients with empiric antibiotics has declined during the pandemic, the frequency of use remains high. There is significant inter-center variation in antibiotic prescribing practices and evidence of potential harm. Our findings are hypothesis-generating and future work should prospectively compare outcomes and adverse events.

KW - COVID-19

KW - antimicrobial prescribing

KW - bacterial coinfection

KW - drug resistance

KW - pneumonia

UR - http://www.scopus.com/inward/record.url?scp=85168251224&partnerID=8YFLogxK

U2 - 10.1097/CCM.0000000000005901

DO - 10.1097/CCM.0000000000005901

M3 - Article

C2 - 37125800

AN - SCOPUS:85168251224

SN - 0090-3493

VL - 51

SP - 1168

EP - 1176

JO - Critical care medicine

JF - Critical care medicine

IS - 9

ER -

Early Empiric Antibiotic Use in Patients Hospitalized With COVID-19: A Retrospective Cohort Study

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