Resilience and emergence of pneumococcal serotypes and lineages in adults post-PCV13 in Spain: A multicentre study

Abstract

Background: Streptococcus pneumoniae causes invasive pneumococcal disease (IPD) in adults. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced vaccine serotypes but has also led to the rise of non-vaccine serotypes. The aim of this study was to analyse pneumococcal lineages and their association with recent changes in IPD among adults in Spain. Methods: Data from adult IPD cases (≥18 years) were collected from six Spanish hospitals in 2019-2021. Strains were serotyped, tested for antibiotic susceptibility and subjected to whole genome sequencing (WGS). Findings were compared with data from previous periods (2008-2016). Results: A total of 655 IPD episodes were examined. Pneumonia was the main focus (515/655), and 366 episodes occurred in adults over 64 years. Although IPD incidence decreased during COVID-19 pandemic, the burden of disease caused by PCV13 serotypes was significant. Notably, serotype 3 persisted (GPSC12-ST180 and GPSC83-ST260), and a new serotype 4 lineage emerged (GPSC162-ST13022). Among non-PCV13 serotypes, serotype 8 expanded (GPSC3-ST53) and a new serotype 12F lineage emerged (GPSC55-ST8060). Most serotypes presented a dominant Global Pneumococcal Sequencing Cluster (GPSC) like GPSC16-ST67 of 9N or GPSC19-ST433 of 22F. Nevertheless, some GPSCs were associated with several serotypes, the most numerous were GPSC3 (serotypes 8, 11A, and 33F) and GPSC6 (serotypes 11A and 14). The overall penicillin non-susceptibility rate was 17.0 %, 14.6 % resistance for meningitis and 1.6 % for pneumonia (15.1 % susceptible at increased exposure [SIE]). Serotypes 11A and 14 (GPSC6-ST156/6521) and 19A (GPSC1-ST320) had penicillin MICs above 1 mg/L. Acquired resistance genes associated with macrolide and/or tetracycline resistance were present in 19.4 % of isolates, particularly among serotypes 6C (GPSC47-ST386/4310) and 19A (GPSC1-ST320). Conclusions: The burden of PCV13 serotypes in adult IPD remains significant, and serotype 3 is the primary contributor. However, the rise of stable lineages associated with non-PCV13 serotypes, particularly 8, 9N, and 22F highlights a shifting epidemiology. The persistence of multidrug-resistant lineages, such as GPSC6-ST156 and GPSC1-ST320, emphasizes the need for continued surveillance. Vaccination of high-risk adults with current and broader coverage PCVs would help to control the burden of pneumonia and IPD among adults.