Serotype replacement and mobile genetic elements in Streptococcus pneumoniae: a systematic review

Streptococcus pneumoniae causes otitis media and severe diseases including pneumonia, meningitis and bacteraemia. The rise of antimicrobial resistance (AMR) in S. pneumoniae, facilitated by mobile genetic elements (MGEs), complicates infection treatment. While pneumococcal conjugate vaccine (PCV) deployment has reduced disease burden, non-vaccine serotypes (NVTs) have increased and now cause invasive disease. Although PCV reduced the overall AMR incidence, AMR prevalence among NVT pneumococci has increased, creating dual challenges of MGE-driven AMR spread and serotype replacement. In this review, we analysed geographical patterns of serotype replacement and the role of MGE-driven AMR in S. pneumoniae using predefined search terms related to pneumococcus, MGEs and serotype replacement. Search outputs were managed through COVIDENCE. We de-duplicated 3,634 articles, screened 2,085 by title/abstract, assessed 423 based on exclusion criteria, reviewed 298 full texts and included 70 studies meeting our inclusion criteria. Global data revealed reductions in vaccine serotypes following vaccination, with concurrent NVT increases. Tn916-like and Tn5253-like integrative and conjugative elements (ICEs) were associated with tetracycline and macrolide resistance mobilization. Multidrug-resistant NVTs (15A, 15C, 23A, 34 and 35B) continue emerging globally. Our analysis further reinforces other findings that while PCV implementation has successfully reduced vaccine serotype pneumococcal prevalence globally, this success is accompanied by substantial serotype replacement across all continents. This shifting landscape is further complicated by the widespread presence of MGEs mediating AMR in both vaccine and NVTs, particularly through Tn916-like and Tn5253-like ICEs. These dual challenges underscore the urgent need for improved antimicrobial stewardship programmes and the development of serotype-independent vaccines.