Related Experiment Video
Updated: Mar 20, 2026

Constructing Mutants in Serotype 1 Streptococcus pneumoniae strain 519/43
Published on: September 11, 2020
Multidrug Resistance in Non-PCV13 Serotypes of Streptococcus pneumoniae in Northern Japan, 2014
Mitsuyo Kawaguchiya1, Noriko Urushibara1, Nobumichi Kobayashi1
1Department of Hygiene, Sapporo Medical University School of Medicine , Sapporo, Japan .
Abstract:
Since the implementation of routine PCV13 immunization in Japan, nonvaccine serotypes (NVTs) have been increasing among clinical isolates of Streptococcus pneumoniae. In this study, susceptibility to 18 antibiotics was tested for all the 231 isolates with NVTs, which were collected from children <16 years of age in northern Japan in 2014 (July-November). High resistance rates were observed for macrolides (>90.9%), tetracycline (91.3%), and clindamycin (75.3%), while penicillin (PEN) nonsusceptibility (PNSP; MIC ≥0.12 μg/ml) was detected in 42.9% of the pneumococci [39.4%; PEN-intermediate S. pneumoniae (PISP), 3.5%; PEN-resistant S. pneumoniae (PRSP)]. All serotype 15A isolates were PRSP (MIC, ≥2 μg/ml) or PISP, and PNSP was prevalent in also serotypes 23A (96.9%), 6C (41%), and 35B (33.3%). Overall, 42.0% of the isolates showed multidrug resistance (MDR). Sequence types (STs) determined for 20 PNSP isolates with NVTs were ST63 (15A), STs 242 or 5832 (6C), STs 338 or 5242 (23A), and ST558 (35B). All the PNSP isolates possessed tet(M), and erm(B) or mefA(A/E), and 70% of them were gPRSP having three altered genes pbp1a, pbp2x, and pbp2b. Among alterations in transpeptidase-coding region of penicillin-binding proteins (PBPs), two substitutions of T371S in the STMK motif and TSQF574-577NTGY in PBP1a were common to all PRSP isolates. The present study showed the spread of PNSP in NVTs 15A, 23A, 6C, and 35B, and the emergence of the MDR international clone Sweden15A-ST63 in northern Japan.
Insights
Nonvaccine serotypes of Streptococcus pneumoniae are increasing in Japan following PCV13 immunization. High rates of antibiotic resistance, including penicillin nonsusceptibility, were found in clinical isolates from children, with some strains showing multidrug resistance.
Area of Science:
- Microbiology
- Infectious Diseases
- Public Health
Background:
- Routine pneumococcal conjugate vaccine (PCV13) implementation in Japan has coincided with an increase in nonvaccine serotypes (NVTs) of Streptococcus pneumoniae.
- These NVTs are increasingly detected in clinical isolates, necessitating surveillance of their antimicrobial resistance patterns.
Purpose of the Study:
- To investigate the antibiotic susceptibility profiles of NVTs of Streptococcus pneumoniae isolated from children in northern Japan.
- To identify the prevalence of penicillin nonsusceptibility (PNSP) and multidrug resistance (MDR) among these NVT isolates.
Main Methods:
- Antimicrobial susceptibility testing against 18 antibiotics was performed on 231 NVT Streptococcus pneumoniae isolates collected from children under 16 years old.
- Molecular methods, including sequencing type (ST) determination and analysis of resistance genes and penicillin-binding protein (PBP) alterations, were used for PNSP isolates.
Main Results:
- High resistance rates were observed for macrolides (>90.9%), tetracycline (91.3%), and clindamycin (75.3%).
- Penicillin nonsusceptibility (PNSP) was detected in 42.9% of isolates, with high prevalence in serotypes 15A, 23A, 6C, and 35B.
- Overall, 42.0% of isolates exhibited multidrug resistance (MDR), and the international clone Sweden15A-ST63 was identified.
Conclusions:
- The study highlights the significant spread of PNSP among NVTs, particularly serotypes 15A, 23A, 6C, and 35B, in northern Japan.
- The emergence of MDR strains, including the Sweden15A-ST63 clone, poses a growing public health concern and underscores the need for ongoing surveillance.
Related Concept Videos
Mechanism of Antibiotic Resistance in MRSA
Development of Antibiotic Resistance
Clinical Significance of Antibiotic Resistance
Atypical Pneumonia
Antibiotic Selection
Antimicrobial Effectiveness

