Spread of Meropenem-Resistant Streptococcus pneumoniae Serotype 15A-ST63 Clone in Japan, 2012-2014.

After the introduction of pneumococcal conjugate vaccines, the incidence of pneumococcal infections due to meropenem-resistant serotype 15A-ST63 strains increased in Japan. By using whole-genome sequencing and comparing sequences with those of clones from the United Kingdom, the United States, and Canada, we clarified the traits of the serotype 15A-ST63 clone. Our analysis revealed that the meropenem-resistant serotype 15A-ST63 strains from Japan originated from meropenem-susceptible strains from Japan. Recombination site prediction analysis showed that the meropenem-resistant strain-specific recombination regions included the pbp1a and pbp2b regions. A detailed analysis of the composition of these genes indicated that resistance seems to be caused by pbp1a recombination. The pbp1a gene in meropenem-resistant isolates was identical to that in multidrug (including meropenem)-resistant serotype 19A-ST320 pneumococci, which have spread in the United States. The global spread of pneumococci of this lineage is noteworthy because serotype 15A is not included in the currently used 13-valent pneumococcal conjugate vaccine.

Emergence of an extensively drug-resistant (XDR) Streptococcus pneumoniae serotype 15A by capsular switching.

Recently, we have identified an extensively drug-resistant (XDR) Streptococcus pneumoniae serotype 15A isolate from a patient with bacterial meningitis. It belonged to sequence type 8279 (ST8279), a clone identified as XDR serotype 11A isolated in South Korea. We obtained and compared the genome sequences of an XDR 15A and an XDR 11A isolate. The genomes of two XDR isolates were highly identical, except for the capsular polysaccharide (cps) locus and another small region. Capsular switching from 11A to 15A may have occurred via recombination of the cps locus. The emergence of a new XDR clone via capsular switching would be a great concern for public health and in clinical settings.

Multidrug-resistant Streptococcus pneumoniae causing invasive pneumococcal disease isolated from a paediatric patient.

The emergence of non-vaccine multidrug-resistant Streptococcus pneumoniae serotypes is on rise. This study was performed to investigate a highly resistant serotype 15A S. pneumoniae isolated from the blood specimen of a 20-month-old patient who died of her infection. The SS40_16 isolate was resistant to erythromycin, co-trimoxazole, tetracycline, and chloramphenicol, as well as to penicillin, ceftriaxone, and cefotaxime (using meningitis cut-off points, Clinical and Laboratory Standards Institute). The isolate belonged to sequence type 1591 (ST1591) and was related to CC81 clonal complex, suggesting the possibility of horizontal gene transfer. Scanning electron microscopy comparison between resistant and sensitive pneumococcal isolates also indicated similar phenotypic characteristics that confer high resistance. The emergence of highly resistant non-vaccine pneumococci is of great concern to public health and in the clinical setting. Pneumococcal surveillance programs represent a crucial tool, not only for determining the impact of pneumococcal conjugate vaccines, but also for monitoring the selective pressure of serotype replacement with regard to the treatment of invasive pneumococcal disease.

A multiple drug-resistant Streptococcus pneumoniae of serotype 15A occurring from serotype 19A by capsular switching.

Streptococcus pneumoniae is a highly recombinogenic pathogen. The ability of pneumococci to acquire and incorporate exogenous DNA is an important evolutionary mechanism for adaptation to clinical interventions such as antibiotic therapy and vaccination. Herein, using whole genome sequencing we detected a multiple drug-resistant serotype 15A pneumococcus emerged by capsular switching from serotype 19A/ST276. The dissemination of recombinant multiple drug-resistant pneumococcal clones with non-vaccine type capsule is of concern and warrants thorough monitoring of serotype and genotype structure within pneumococcal populations.

Invasive pneumococcal infection due to serotype 15A after the pneumococcal conjugate vaccine implementation in Turkey.

Invasive pneumococcal infections among children are a serious public health problem in many countries, including Turkey. Pneumococcal conjugate vaccine has been included in Turkey's National Immunization Programme since 2009. We report the first two pediatric cases of invasive pneumococcal infection due to non-vaccine serotype 15A after pneumococcal conjugate vaccine implementation in Turkey. It is essential to monitor the countries' own local seroepidemiologic data for detecting selective pressure of non-vaccine serotypes of S. pneumonia.

Multidrug Resistance in Non-PCV13 Serotypes of Streptococcus pneumoniae in Northern Japan, 2014.

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.