Impact of Pneumococcal Conjugate Vaccine 13 on Invasive Pneumococcal Diseases and Antibiotic Prescribing in the United Kingdom

Background: In April 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the childhood immunisation programme in the United Kingdom (UK) to protect against additional serotypes that caused invasive pneumococcal diseases (IPDs) not covered by PCV7. Current evidence on the impact of PCV13 on childhood IPDs and associated antibiotic prescribing in the community is limited.

Objectives: To evaluate the impact of PCV13 on the incidence of IPDs, antibiotic prescribing and mortality related to IPD in UK children aged 0-18 years.

Methods: A retrospective population-based study was conducted using the UK IQVIA Medical Research Data (IMRD) between Jan 2008 and Dec 2019. A 14‐day screening period was used to define each IPD episode. The monthly incidence rate was calculated as the number of IPD episodes divided by the person-months. Interrupted time series analysis (ITS) was performed to compare the IPD incidence and antibiotic prescribing between the pre-PCV13 (Jan 2008-Mar 2010) and post-PCV13 periods (Apr 2010-Dec 2019). Incidence rate ratios (IRR) with 95% confidence intervals (CI) were estimated. All analyses were stratified by age groups ( < 2, 2-4, 5-9 and 10–18-year-olds). Antibiotic prescribing patterns were assessed according to the 2021 WHO AWaRe (Access, Watch and Reserve) classification. Cox proportional hazards regression was performed to estimate the impact of PCV13 introduction on IPD-related mortality, adjusted by age, gender and deprivation index. Sensitivity analyses were carried out by extending the 14-day screening period to 21 and 30 days.

Results: A total of 24,178 IPD episodes were identified in 21,463 children. The highest incidence rate of IPDs was observed in children under 2, followed by 2-4, 5-9 and 10-18 years old. After the introduction of PCV13, there was an immediate 22% decrease in IPD incidence for all age groups (IRR: 0.78; 95% CI: 0.68, 0.88). A gradual decline in IPD incidence was observed post-PCV13 (IRR: 0.99; 95% CI: 0.98, 0.99). Similarly, an immediate 33% decline in the incidence of antibiotic prescribing was observed (IRR: 0.67; 95% CI: 0.57, 0.78) shortly after PCV13 introduction. There was a gradual decline in antibiotic prescription rate post‐PCV13 (IRR: 0.98; 95% CI: 0.97, 0.99). The use of Access antibiotics increased from 84.49% to 86.03% whilst Watch antibiotics decreased from 15.51% to 13.72%. There was numerically decline in IPD-related mortality in the post-PCV13 period which does not reach statistical significance (HR: 0.29; 95% CI: 0.07, 1.25).

Conclusions: The study found a lower burden of IPDs and associated antibiotic prescribing after the introduction of PCVs. Continuous monitoring of IPDs is warranted due to ongoing serotype replacement, to inform decisions about the introduction of higher valent PCVs.