Background <p>This study aimed to describe community antibiotic use for respiratory and urinary tract infections (UTIs), in Quebec, from 2018 to 2022 and to assess the joint effect of comorbidities and the COVID-19 pandemic on prescription concordance with provincial guidelines.</p> Methods <p>A retrospective analysis was conducted using medical and pharmaceutical claims data from 2018 to 2022 for individuals insured by the public health and drug plans. Data were sourced from the Quebec Integrated Chronic Disease Surveillance System (QICDSS), linking five administrative databases. The primary outcome was the proportion of prescriptions concordant with the provincial guidelines for the most frequent infections in children and adults. Prescriptions dispensed within two days of a medical diagnosis for eligible infections were included. Robust Poisson regressions assessed the joint impact of number of comorbidities and pandemic period on concordance.</p> Results <p>In children, over 90% of antibiotic prescriptions were concordant with guidelines. Lower concordance was observed for pneumonias and pharyngitis among children with comorbidities. In adults, concordance varied by infection type and declined with increasing comorbidities. Concordance improved during the pandemic and after for UTIs and rhinosinusitis, but decreased for pneumonias. No significant interactions were found between comorbidities and pandemic periods, except for bronchitis with chronic obstructive pulmonary disease (COPD).</p> Conclusion <p>In Quebec, comorbidities were associated with decreased adherence to clinical guidelines for antibiotic prescribing, particularly among adults. The COVID-19 pandemic had minimal influence on concordance.</p> Clinical trial number <p>Not applicable.</p>