Global mapping of Streptococcus pneumoniae sequence types associated with multidrug resistance and capsular switching: A systematic review

Background: Streptococcus pneumoniae is a significant bacterial pathogen responsible for invasive and non-invasive infections. One of its most concerning traits is capsular switching, which may contribute to multidrug resistance (MDR) and emergence of difficult-to-treat infections. This systematic review examined the sequence types of S. pneumoniae associated with MDR and/or capsular switching, focusing on their genetic relatedness. Methodology: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. A comprehensive literature search was performed across PubMed, Scopus, and Web of Science. Studies published between 1991 and 2024 were screened based on predefined inclusion criteria. Eligible studies documented sequence types associated with MDR and/or capsular switching. Results: Through a review of 133 studies across 152 countries, we identified dominant MDR sequence types: ST177, ST63, ST199, ST156, ST242, and ST338, and their genetic relationships with other MDR lineages. Notably, we compiled 390 documented capsular switching events spanning 184 distinct sequence types, providing a broad global synthesis of capsular switching in S. pneumoniae. We observed common trends of switching from vaccine to non-vaccine serotypes, alongside within-serogroup switching and within-vaccine group switching, predominantly in the post-vaccination era. Conclusion: Findings underscore a rapidly evolving genetic landscape of S. pneumoniae, in which MDR lineages diversify through capsular switching and serotype replacement. Despite (Pneumococcal Conjugate Vaccine) PCV introduction, vaccine-type MDR clones persist, raising concerns for serotypes such as 3, 6A/B, 19F, 14, and 23F. In addition, the global distribution and MDR profiles of ST320 and ST271 support their consideration as potential new (Pneumococcal Molecular Epidemiology Network) PMEN clone candidates, reinforcing the need for sustained genomic surveillance in the post-PCV era.