Unraveling the Impact of Pneumococcal Conjugate Vaccines on Ambulatory Antibiotic Drug Consumption in Young Children: An Interrupted Time-Series Analysis

Background. Pneumococcal conjugate vaccines (PCVs) reduce respiratory infections in young children, the main antibiotic consumers. Following PCV implementation, dispensed antibiotic prescription (DAP) rates in young children were expected to decline. Methods. Computerized data on DAP for children <5 years were examined during a 13-year period (including 4 pre-PCV years). All DAPs from clinics with ≥50 insured children, active both pre-and post-PCV implementation were included. Interrupted time-series with segmented regression was applied to analyze monthly DAP rate trends, adjusted for age, ethnicity, and season. Incidence rate ratios (IRRs) of DAPs during the late PCV13 period versus 4 years pre-PCV were calculated both as absolute rate ratios (aIRRs) and relative to expected rates (rIRRs). Results. Of 1 090 870 DAPs, 57% were in children <2 years. All-DAP rates peaked in the cold season. Post-PCV7/PCV13 implementation, all DAP rates abruptly and significantly declined, reaching a plateau within 5 years. This was largely driven by amoxicillin/ amoxicillin-clavulanate (75% of DAPs). Age <2 years and Bedouin ethnicity were significantly associated with higher pre-PCV DAP rates but with faster and greater decline post-PCV, achieving near elimination of gaps between ages and ethnic groups. Overall reduction (95% CIs) in DAP rates per 1000 was estimated between aIRR (344.7 [370.9-358.4]) and rIRR (110.4 [96.9-123.7]) values. Conclusions. Shortly following PCV implementation, overall DAP rates showed an abrupt, steep decline, stabilizing within 5 years, in parallel to post-PCV respiratory infection trends previously described in this population, suggesting causality. The variable patterns of certain drug categories suggest additional influences beyond PCV.