Trends in Outpatient Antibiotic Prescriptions in the United States During the COVID-19 Pandemic in 2020

Following the arrival of COVID-19 in the US, there were significant reductions in prescription fills with commonly prescribed outpatient antibiotics in April 2020.¹ Through July 2020, monthly azithromycin, amoxicillin, amoxicillin-clavulanate, and levofloxacin prescription fills did not rebound significantly.¹ In this cross-sectional study, we measured prescription fills of commonly prescribed outpatient antibiotics in the US through the end of 2020.

This cross-sectional study was found exempt by the institutional review board at the University of Pittsburgh. Informed consent was waived because data was deidentified. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

During each quarter, the mean monthly prescription fills for 9 of the 10 most commonly prescribed US outpatient antibiotics (excluding sulfamethoxazole-trimethoprim) was found from IQVIA National Prescription Audit data (Figure).¹ A nonlinear least squares regression model was used to anticipate mean monthly prescription fills during quarters of 2020 based on 2015 to 2019 data. Anticipated and actual mean monthly fills each quarter were compared by a 2-tailed t test. Statistical significance was set at P < .05. STATA/SE version 16.1 (StataCorp) was used for statistical analysis.

In quarter 1 of 2020 (ie, January-March), the mean monthly prescription fills of each agent did not significantly differ from anticipated values (Table). In quarter 2 (ie, April-June), quarter 3 (ie, July-September), and quarter 4 (ie, October-December 2020), the mean monthly amoxicillin, amoxicillin-clavulanate, and doxycycline fills were significantly lower than anticipated (amoxicillin: 25.3%-44.1%; P = .003-.03; amoxicillin-clavulanate: 30.1%-40.0%; P = .005-.02; doxycycline: 17.8%-20.7%; P = .008-.01). Azithromycin fills were significantly lower than anticipated in quarters 2 and quarter 4 (quarter 2: 35.4% decrease; P = .02; quarter 4: 31.8% decrease; P = .03). The decrease in quarter 3 was not significant (22.1% decrease; P = .06).

Mean monthly cephalexin fills were 10.1% lower than anticipated in quarter 4 (P = .05); those of clindamycin were 4.8% lower than anticipated in quarter 3 (P = .04). Mean monthly ciprofloxacin fills were 12.2% and 14.3% higher than anticipated in quarters 3 and 4, respectively (P = .001 and P = .04). Nitrofurantoin and levofloxacin fills were not significantly different from projections in quarter 2, 3, and 4.

This study is the first report of the impact of COVID-19 on US outpatient antibiotic prescriptions throughout 2020. The data tell a mixed story. In April, significant reductions in mean monthly fills of the 4 most commonly prescribed outpatient agents (ie, amoxicillin, azithromycin, amoxicillin-clavulanate, doxycycline) persisted throughout 2020, compared to estimations based on prepandemic trends. However, significantly higher-than-anticipated mean monthly ciprofloxacin fills in quarter 3 and quarter 4 reversed a 5-year trend of consistent reductions in outpatient ciprofloxacin use.^2,3 For other outpatient antibiotics, previously reported decreases in seasonally adjusted prescriptions in April 2020 were not maintained over the remainder of the year.¹

Reasons for prescription patterns are unclear. The US Centers for Disease Control estimated that 39% to 41% of adults delayed or deferred medical care in quarter 2, 32% to 41% in quarter 3, and 31% to 35% in quarter 4.⁴ Amoxicillin, azithromycin, amoxicillin-clavulanate, and doxycycline are often used to manage respiratory tract infections.⁵ It is possible that widespread masking and other COVID-19 preventive measures resulted in fewer bacterial respiratory infections, decreased incidence of influenza or other viral infections led to less inappropriate antibiotic use, and clinicians appreciated that SARS-CoV-2 and other viral infections did not require antibiotic treatment.⁶ Lack of sustained reductions in cephalexin and clindamycin fills may reflect primary use against urinary tract and skin or soft tissue infections, respectively. Past reductions in ciprofloxacin use were primarily because of changes in managing urinary tract infections rather than respiratory syndromes.³

Patient-level data and information on International Classification of Diseases, Ninth Revision codes, and unfilled prescriptions were unavailable, which limited our ability to identify factors associated with prescription fills. Agents included here accounted for over 80% of outpatient antibiotic fills captured by IQVIA; patterns may differ for other agents. We cannot exclude an association of factors unrelated to COVID-19, such as greater attention to antibiotic stewardship. Further studies of antibiotic consumption during the COVID-19 pandemic are needed, with particular attention to drivers and appropriateness of use, regional differences, and antibiotic resistance.

Accepted for Publication: July 19, 2021.

Published: September 22, 2021. doi:10.1001/jamanetworkopen.2021.26114

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Buehrle DJ et al. JAMA Network Open.

Corresponding Author: Cornelius J. Clancy, MD, VA Pittsburgh Healthcare System, 3550 Terrace St, Scaife Hall 867, Pittsburgh, PA 15261 (cjc76@pitt.edu).

Author Contributions: Dr Clancy and Dr Buehrle had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Buehrle, Nguyen, Clancy.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Buehrle, Clancy.

Critical revision of the manuscript for important intellectual content: Buehrle, Wagener, Nguyen.

Statistical analysis: Wagener, Nguyen, Clancy.

Supervision: Buehrle, Clancy.

Conflict of Interest Disclosures: Dr Nguyen reported receiving grants from Astellas, Merck, Melinta, and Cidara outside the submitted work and reported serving on advisory boards for Astellas, Merck, the Medicines Company, Scynexis, and Shionogi. Dr Clancy reported receiving grants from Astellas, Merck, Melinta, and Cidara outside the submitted work, serving on advisory boards or consulting for Astellas, Merck, the Medicines Company, Cidara, Scynexis, Shionogi, Qpex, and Needham and Company, and being a speaker at a symposium sponsored by Merck and T2Biosystems. Dr Buehrle reported serving on an advisory board for Shionogi outside the submitted work. No other disclosures were reported.

Additional Contributions: The authors thank Alan Carr, PhD (Needham and Company) for his assistance with obtaining and interpreting IQVIA National Prescription Audit data. Dr Carr did not receive compensation.