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ABSTRACT Objective: The quality of care and safety for Telemedicine-discharged patients with suspected respiratory infections are closely related to low rates of prescriptions of unjustified and high-risk medications. This retrospective study aimed to assess adherence to the current COVID-19 guidelines in direct-to-consumer telemedicine encounters at a large center using multidrug stewardship protocols. Methods: A quarterly electronic survey utilizing medical records of individual physician care assessed various quality indicators. Physicians received ongoing adaptive feedback based on personal metrics, with Telemedicine Center recommendations derived from the 2020 Infectious Diseases Society of America guidelines. The study included all consecutive adults with new respiratory symptoms in the last 14 days who sought spontaneous Telemedicine consultations between March 2020 and August 2021. This study analyzed patients with suspected or confirmed COVID-19 and other airway infections. Results: Of the 221,128 evaluated patients, 42,042 (19%) had confirmed COVID-19; 104,021 (47%) were suspected to have COVID-19; and, 75,065 (33%) had other diagnoses. Patients with suspected or confirmed COVID-19 had a mean (+DP) age of 35±12 years. A total of 125,107 (85.65%) patients were managed at home, 2,552 (1.74%) were referred for non-urgent in-office reassessment, and 17,185 (11.7%) were referred to the emergency department for whom there was no further treatment recommendation. The antibiotic rate in confirmed or suspected COVID-19 cases was 0.46%/0.65% and that for non-evidence-based prescriptions was 0.01%/0.005%. Conclusion: Guideline training and Telemedicine consultation feedback may lead to lower antibiotic and antimicrobial prescriptions in suspected and confirmed COVID-19 cases. Multidrug stewardship protocols may improve guideline adherence and reinforce the quality of care and safety in Telemedicine encounters. Objective Telemedicinedischarged discharged highrisk high risk medications COVID19 COVID 19 COVID-1 directtoconsumer direct consumer Methods indicators metrics 202 1 2021 Results 221128 221 128 221,12 42042 42 042 42,04 19% (19% 104021 104 021 104,02 47% 47 (47% 75065 75 065 75,06 33% 33 (33% diagnoses +DP DP (+DP 3512 35 12 35±1 years 125107 125 107 125,10 85.65% 8565 85 65 (85.65% home 2552 2 552 2,55 1.74% 174 74 (1.74% nonurgent non urgent inoffice office reassessment 17185 17 185 17,18 11.7% 117 11 7 (11.7% recommendation 046065 0 46 0.46%/0.65 nonevidencebased evidence 0010005 01 005 0.01%/0.005% Conclusion COVID1 COVID- 20 22112 22 221,1 4204 4 04 42,0 (19 10402 10 02 104,0 (47 7506 06 75,0 3 (33 351 35± 12510 125,1 85.65 856 8 6 (85.65 255 55 2,5 1.74 (1.74 1718 18 17,1 11.7 (11.7 04606 0.46%/0.6 001000 00 0.01%/0.005 2211 221, 420 42, (1 1040 104, (4 750 75, (3 1251 125, 85.6 (85.6 25 5 2, 1.7 (1.7 171 17, 11. (11. 0460 0.46%/0. 00100 0.01%/0.00 ( 85. (85. 1. (1. (11 046 0.46%/0 0010 0.01%/0.0 (85 0.46%/ 001 0.01%/0. (8 0.46% 0.01%/0 0.46 0.01%/ 0.4 0.01% 0. 0.01 0.0