The impact of pneumococcal conjugate vaccines on disease epidemiology, serotype distribution, and antimicrobial resistance in children. A 25-year observational study in Athens, Greece (1996-2021).

Streptococcus pneumoniae continues to cause invasive pneumococcal disease (IPD) and non-IPD in children, despite widely implemented pneumococcal conjugate vaccines (PCVs). This study evaluated the impact of PCV7 and PCV13 on pneumococcal disease (PD), serotype distribution, and antimicrobial resistance in children ≤14 years in Athens, Greece. We conducted a retrospective multicenter study in five pediatric hospitals covering ~80% of Athens' pediatric population in three time periods; pre-PCV (1996-2005), post-PCV7 (2006-2010), and post-PCV13 (2011-2021). Clinical, microbiological, and demographic data were collected for children with PD. Capsular typing was performed by the Quellung reaction. Untypeable or antiserum cross-reacting isolates were typed by Next Generation Sequencing (NGS). The minimal inhibitory concentrations (MICs) were determined by Etest. A total of 2546 children with PD were identified and included in the analysis; 1233 (48.4%) with IPD and 1313 (51.6%) with non-IPD. PCVs significantly impacted disease patterns: IPD declined from 59% in the pre-PCV period to 35.1% in post-PCV13, while age distribution shifted toward older children (p < .001). All PCV7/13 serotypes decreased significantly in the post-PCV periods, except serotype 3 which increased, contributing substantially to empyema cases. Vaccine failures were 9.8% of cases, mostly attributed to serotypes 3, 19A, and 19F. Multidrug resistance (MDR) rates rose from 12.9% in pre-PCV to 24.8% in post-PCV13 period (p < .001), with MDR serotypes 19F and 23F decreasing over time and 19A becoming the predominant MDR phenotype (47.1%) in the post-PCV13 era. These findings underscore the dynamic nature of PD in the post-PCV era and highlight the ongoing need for surveillance studies, vaccine updates and resistance monitoring.