Over the last years, the susceptibility activity of the most common microorganisms causing community-acquired infections has significantly changed in Spain. Based on the susceptibility rates of Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, and Klebsiella pneumoniae collected from outpatients aged 15 or older with symptoms of respiratory or urinary tract infections in several Microbiology Departments in Catalonia in 2021, penicillin V should be first choice for most respiratory tract infections, amoxicillin and clavulanate for chronic obstructive pulmonary disease exacerbations and a single dose of fosfomycin or a short-course nitrofurantoin should remain first-line treatments for uncomplicated urinary tract infections. Updated information on antimicrobial resistance for general practitioners is crucial for achieving appropriate empirical management of the most common infections by promoting more rational antibiotic use.