- Background: Bacteremic pneumonia (BP) accounts for ~35% of invasive pneumococcal disease (IPD) in young children. Our aims were to compare age, seasonal and serotype distribution of BP versus non-BP IPD and to determine whether the impact of the sequential 7/13-valent pneumococcal conjugate vaccine (PCV7/PCV13) introduction on disease incidence differed between BP and non-BP IPD in children <5 years of age. Methods: A nationwide, prospective, population-based, active surveillance (July 2004–June 2013) was conducted. All IPD episodes were included. PCV7 was introduced to the Israeli National Immunization Plan in July 2009 and has been replaced by PCV13 since November 2010. Results: In all, 983 (36.8%) BP and 1687 (63.2%) non-BP IPD episodes were recorded. A higher proportion of BP than that of non-BP IPD episodes (42.0% vs. 20.7%; P < 0.001) occurred in children >24 months old. Seasonality differed between BP and non-BP IPD, with yearly earlier peaks of non-BP IPD. The proportion of the 5 additional PCV13 serotypes (1, 3, 5, 7F and 19A) was higher in children with BP versus non-BP IPD (39.6% vs. 23.6%; P < 0.01). Shortly after PCV7 introduction, non-BP IPD rate was significantly reduced but that of BP was not. However, PCV13 introduction resulted in rapid reduction of BP rate, with a further reduction of non-BP IPD. Conclusion: The differences in age distribution, seasonality and serotype distribution between BP and non-BP IPD suggest that the pathogenesis of these 2 entities is not identical and resulted in different impact rate dynamics after PCV7 and PCV13 introduction.