High isolation rate and multidrug resistance tendency of penicillin-susceptible group B Streptococcus with reduced ceftibuten susceptibility in Japan

  • Hirotsugu Banno
  • Kouji Kimura
  • Tomomi Seki
  • Wanchun Jin
  • Jun-ichi Wachino
  • Keiko Yamada
  • Noriyuki Nagano
  • Yoshichika Arakawa
Original Article


Group B Streptococcus (GBS) clinical isolates with reduced penicillin susceptibility (PRGBS) have emerged through acquisition of amino acid substitutions in penicillin-binding protein 2X (PBP2X). Moreover, we also reported the emergence of penicillin-susceptible GBS clinical isolates with reduced ceftibuten susceptibility (CTBr PSGBS) due to amino acid substitutions in PBPs. However, whether or not these amino acid substitutions are responsible for the reduced ceftibuten susceptibility (RCTBS) profile remains unclear. Furthermore, the rate of CTBr PSGBS isolation and their multidrug resistance tendency remain uncertain. Therefore, we collected 377 clinical GBS isolates from multiple regions in Japan between August 2013 and August 2015. These isolates were characterized by determining MICs and sequencing the pbp2x gene. The isolation rate of CTBr PSGBS was 7.2% (27/377). CTBr PSGBS isolate harbor two types of amino acid substitutions in PBP2X [(T394A type) and (I377V, G398A, Q412L, and H438H type)]. The relevance of the amino acid substitutions found to the RCTBS was confirmed with allelic exchange techniques. Allelic exchange recombinant clones acquired two types of amino acid substitutions in PBP2X showed RCTBS. Furthermore, total ratio of resistance and non-susceptibility to both macrolides and fluoroquinolones in CTBr PSGBS was 51.9% (14/27). The isolation rate of CTBr PSGBS is non-negligibly high and the CTBr PSGBS tends to exhibit resistance and non-susceptible profile to both macrolides and fluoroquinolones.


Group B Streptococcus Reduced ceftibuten susceptibility Penicillin-binding protein 2X Multidrug resistance 



We wish to thank all members of Professor Yoshichika Arakawa’s laboratory for technical advice and valuable discussions. The manuscript was edited by Editage, a language editing company.


This work was supported by the Emerging/Re-emerging Infectious Disease Project of the Japan Agency for Medical Research and Development, AMED.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

As this study pertains to the characterization of bacterial isolates only, and as we did not obtain or use clinical or personal information, this type of study does not require examination or approval of an ethical committee according to the related guidelines of the Japanese government.

Informed consent

Informed consent is not applicable, as this article does not contain any studies with human participants.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hirotsugu Banno
    • 1
  • Kouji Kimura
    • 1
  • Tomomi Seki
    • 1
  • Wanchun Jin
    • 1
  • Jun-ichi Wachino
    • 1
  • Keiko Yamada
    • 1
  • Noriyuki Nagano
    • 2
  • Yoshichika Arakawa
    • 1
  1. 1.Department of BacteriologyNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Department of Health and Medical SciencesShinshu University Graduate School of MedicineNaganoJapan

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