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Background: Although Italian pediatric antimicrobial prescription rates are among the highest in Europe, little action has been taken to improve the appropriateness of antimicrobial prescriptions. The primary aim of this study was to assess changes in antibiotic prescription before and after acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis Clinical Pathway (CP) implementation; secondary aims were to compare treatment failures and to assess change in the total antibiotics costs before and after CP implementation., Methods: Pre-post quasi-experimental study comparing the 6-month period before CP implementation (baseline period: October 15, 2014, through April 15, 2015) to the 6 months after intervention (postintervention: October 15, 2015, through April 15, 2016)., Results: Two hundred ninety-five pre- and 278 postintervention emergency department visits were associated with AOM. After CP implementation, there was an increase in "wait and see" approach and a decrease in overall prescription of broad-spectrum antibiotics from 53.2% to 32.4% (P < 0.001). One hundred fifty-one pre- and 166 postimplementation clinic visits were associated with GAS pharyngitis, with a decrease in broad-spectrum prescription after CP implementation (46.4% vs. 6.6%; P < 0.001). For both conditions, no difference was found in treatment failure, and total antibiotics cost was significantly reduced after CP implementation, with a decrease especially in broad-spectrum antibiotics costs., Conclusions: A reduction in broad-spectrum antibiotic prescriptions and a reduction in the total cost of antibiotics for AOM and GAS pharyngitis along with an increase in "wait and see" prescribing for AOM indicate effectiveness of CP for antimicrobial stewardship in this setting.