Rise of multidrug-resistant Streptococcus pneumoniae clones expressing non-vaccine serotypes among children following introduction of the 10-valent pneumococcal conjugate vaccine in Bulgaria

Abstract Objectives Pneumococcal conjugate vaccines (PCVs) have reduced the incidence of pneumococcal disease, but non-vaccine serotypes are of concern, particularly if antimicrobial-resistant. This study retrospectively evaluated the serotype-specific clonality of paediatric multidrug-resistant (MDR) invasive and non-invasive Streptococcus pneumoniae isolates collected following PCV10 introduction (2011–2017) in Bulgaria. Methods Capsular types, drug resistance patterns and multilocus sequence typing (MLST) of the most common MDR S. pneumoniae serotypes sampled from children were determined. Results Overall, the rate of MDR pneumococci was 44.6% (107/240). The most common serotypes among MDR strains were 19F (25.2%), 19A (19.6%), 6C (13.1%), 6A and 23A (6.5% each) and 15A (4.7%), contributing 75.7% of all MDR strains. With the exception of serotype 19F, the remaining serotypes were non-PCV10 types. Among MDR pneumococci, the most frequently found sequence types were ST320 (30.4%; 19A and 19F), ST386 (12.7%; 6C and 6A) and ST8029 (5.1%; 23A). The majority of MDR STs (74.7%) belonged to PMEN clonal complexes, of which the most common were CC320 (Taiwan 19F -14), CC315 (Poland 6B -20) and CC180 (Netherlands 3 -31), accounting for 43.0%, 13.9% and 5.1%, respectively. In the post-vaccine period, a shift in the genetic structure of serotype 19A was found, with a significant increase of PMEN-14 (CC320) and a concurrent decrease of the major clone Denmark 14 -32 (CC230) observed prior to PCV10 introduction in Bulgaria. Conclusions Clonality was found behind the wide distribution of MDR capsular types 19A, 6C, 23A and 3 following vaccine introduction, and a highly multiresistant and virulent clone Taiwan 19F -14/ST320 has emerged as a common pathogen in children.