Clonal lineages and antimicrobial resistance of nonencapsulated Streptococcus pneumoniae in the post-pneumococcal conjugate vaccine era in Japan

•The prevalence rate of Nonencapsulated Streptococcus pneumoniae (NESp) was 1.6% across all study periods.•NESp isolates assigned to null capsule clade 1 (pspK+), 94.4% or 2 (aliC+/aliD+), 5.6%.•Dominant sequences related to sporadic ST1106 lineage or PMEN clone Denmark14-ST230.•Multidrug resistance in 88.7% of NESp isolates (all ST7502, ST4845, ST11379 lineages). The emergence and spread of nonencapsulated Streptococcus pneumoniae (NESp) is a public health concern in the post-pneumococcal conjugate vaccine era. We analyzed the prevalence, molecular characteristics, and antimicrobial resistance of NESp responsible for noninvasive infections in northern Japan. NESp isolates were identified using molecular and phenotypical methods among 4463 S. pneumoniae isolates from noninvasive infection cases during 4 study periods between January 2011 and January 2019. NESp isolates were analyzed for antimicrobial susceptibility, genotype, and virulence-associated genes. Seventy-one NESp isolates were identified (1.6% of total clinical isolates) and assigned to the null capsule clade (NCC)1 (pspK+) (94.4%) or NCC2 (aliC+/aliD+) (5.6%). The dominant sequence types (STs) were ST7502 (23.9%), ST4845 (19.7%), ST16214 (11.3%), ST11379 (9.9%), and ST7786 (7.0%). These 5 dominant STs and all 7 novel STs were related to the sporadic NESp lineage ST1106 or PMEN clone Denmark14-ST230. High non-susceptibility rates of NESp were observed for trimethoprim-sulfamethoxazole, erythromycin, and tetracycline (>92.9%), and multidrug resistance was observed in 88.7% of the NESp isolates, including all ST7502, ST4845, and ST11379 isolates. The study revealed that the dominant clonal groups of NESp were associated with a high prevalence of non-susceptibility to antimicrobials in northern Japan.