Antibiotic Use Patterns and Clinical Outcomes in Hospitalized COVID-19 Patients: A Single-Center Observational Cohort Study with Three-Month Follow-Up.

(1) Background: Antibiotic co-administration during COVID-19 hospitalization is common, but evidence supporting routine use without confirmed bacterial co-infection is limited, and the impact on post-COVID recovery remains largely uninvestigated; (2) Methods: Single-center prospective observational cohort of 127 hospitalized COVID-19 adults (March 2020-December 2024) across four pandemic waves. Antibiotic exposure was the primary variable. Endpoints were 30-day mortality, ICU admission, and persistent dyspnea at three months. Multivariable logistic regression with Firth's penalized profile likelihood 95% CI was performed; ROC analysis assessed procalcitonin (PCT) discrimination; (3) Results: Of 127 patients (median age 70.3 years; 63.8% male; 61.4% unvaccinated), 68 (53.5%) received antibiotics. Notably, 61.5% of patients with PCT ≤ 0.25 ng/mL (viral etiology likely) received antibiotics. After adjustment, antibiotic use was not independently associated with 30-day mortality (OR 0.98, 95% CI 0.27-4.05), ICU admission (OR 1.12, 95% CI 0.31-4.05), or persistent dyspnea at three months (OR 1.51, 95% CI 0.62-4.16). COVID-19 severity was the sole independent mortality predictor (OR 3.563, p = 0.018). At three months, 35.6% reported persistent dyspnea and 14.4% had CT pulmonary fibrosis; (4) Conclusions: Antibiotic exposure did not independently predict short- or long-term outcomes after adjustment for severity, while prescribing was misaligned with PCT-based bacterial probability-supporting biomarker-guided stewardship in epidemic respiratory disease.