Determinants and Temporal Trends of Inappropriate Azithromycin Use in Hospitalized Adults with COVID-19: A Retrospective Pharmacoepidemiologic Cohort Study

Background: The COVID-19 pandemic was associated with extensive empirical antibiotic exposure despite the predominantly viral etiology of the disease. Evaluating patterns of azithromycin use, prescribing determinants, and appropriateness provides insight into real-world antibiotic use under conditions of diagnostic uncertainty. Methods: We performed a retrospective cohort study including 3200 adult patients hospitalized with laboratory-confirmed COVID-19 at the General Hospital in Ferizaj between June 2020 and June 2022. Demographic characteristics, comorbidities, markers of disease severity, laboratory parameters, and antibiotic exposure were extracted from medical records. Azithromycin prescriptions were classified as appropriate, potentially appropriate, or inappropriate based on predefined clinical and laboratory indicators suggestive of bacterial co-infection. Drug utilization patterns, temporal trends, and independent determinants of inappropriate prescribing were assessed using descriptive analyses and multivariable logistic regression modeling. Results: Among 3200 hospitalized patients, 1968 (61.5%) received azithromycin. Of these prescriptions, 612 (31.1%) were classified as appropriate, 418 (21.3%) as potentially appropriate, and 938 (47.6%) as inappropriate. The proportion of inappropriate use decreased over time, from 52.4% in 2020–2021 to 38.7% in 2022 (p < 0.001). However, a substantial proportion of prescriptions remained inappropriate throughout the study period. In multivariable analysis, absence of laboratory markers suggestive of bacterial infection (OR 2.41; 95% CI 1.98–2.93), concomitant use of more than one antibiotic (OR 1.67; 95% CI 1.32–2.11), and lower clinical severity at admission (OR 1.54; 95% CI 1.21–1.95) were independently associated with inappropriate azithromycin prescribing. Conclusions: Azithromycin use was frequent among hospitalized adults with COVID-19, and a considerable proportion of prescriptions lacked clinical or laboratory justification. Although prescribing patterns changed over time, the persistence of inappropriate use highlights ongoing challenges in aligning antibiotic use with emerging evidence. These findings contribute to the understanding of antibiotic utilization patterns in acute care settings and underscore the importance of integrating objective diagnostic indicators into antimicrobial decision-making to strengthen stewardship practice.