Skip to main content
Log in

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

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Farley MM, Harvey RC, Stull T, Smith JD, Schuchat A, Wenger JD, Stephens DS (1993) A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults. N Engl J Med 328:1807–1811. https://doi.org/10.1056/NEJM199306243282503

    Article  PubMed  CAS  Google Scholar 

  2. Heath PT, Balfour G, Weisner AM, Efstratiou A, Lamagni TL, Tighe H, O'Connell LA, Cafferkey M, Verlander NQ, Nicoll A, McCartney AC, Group PGBSW (2004) Group B streptococcal disease in UK and Irish infants younger than 90 days. Lancet 363:292–294. https://doi.org/10.1016/S0140-6736(03)15389-5

    Article  PubMed  Google Scholar 

  3. Jackson LA, Hilsdon R, Farley MM, Harrison LH, Reingold AL, Plikaytis BD, Wenger JD, Schuchat A (1995) Risk factors for group B streptococcal disease in adults. Ann Intern Med 123:415–420. https://doi.org/10.7326/0003-4819-123-6-199509150-00003

    Article  PubMed  CAS  Google Scholar 

  4. Schuchat A (1999) Group B streptococcus. Lancet 353:51–56. https://doi.org/10.1016/S0140-6736(98)07128-1

    Article  PubMed  CAS  Google Scholar 

  5. Skoff TH, Farley MM, Petit S, Craig AS, Schaffner W, Gershman K, Harrison LH, Lynfield R, Mohle-Boetani J, Zansky S, Albanese BA, Stefonek K, Zell ER, Jackson D, Thompson T, Schrag SJ (2009) Increasing burden of invasive group B streptococcal disease in nonpregnant adults, 1990-2007. Clin Infect Dis 49:85–92. http://doi.org/. https://doi.org/10.1086/599369

    Article  PubMed  Google Scholar 

  6. Verani JR, McGee L, Schrag SJ, Division of Bacterial Diseases NCfI, Respiratory Diseases CfDC, Prevention (2010) Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recomm Rep 59:1–36

    PubMed  Google Scholar 

  7. Schuchat A (1998) Epidemiology of group B streptococcal disease in the United States: shifting paradigms. Clin Microbiol Rev 11:497–513

  8. Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A (2002) Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep 51:1–22

    PubMed  Google Scholar 

  9. Kimura K, Suzuki S, Wachino J, Kurokawa H, Yamane K, Shibata N, Nagano N, Kato H, Shibayama K, Arakawa Y (2008) First molecular characterization of group B streptococci with reduced penicillin susceptibility. Antimicrob Agents Chemother 52:2890–2897. https://doi.org/10.1128/AAC.00185-08

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Murayama SY, Seki C, Sakata H, Sunaoshi K, Nakayama E, Iwata S, Sunakawa K, Ubukata K, Invasive Streptococcal Disease Working G (2009) Capsular type and antibiotic resistance in Streptococcus agalactiae isolates from patients, ranging from newborns to the elderly, with invasive infections. Antimicrob Agents Chemother 53:2650–2653. https://doi.org/10.1128/AAC.01716-08

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Nagano N, Nagano Y, Kimura K, Tamai K, Yanagisawa H, Arakawa Y (2008) Genetic heterogeneity in pbp genes among clinically isolated group B Streptococci with reduced penicillin susceptibility. Antimicrob Agents Chemother 52:4258–4267. https://doi.org/10.1128/AAC.00596-08

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Gaudreau C, Lecours R, Ismail J, Gagnon S, Jette L, Roger M (2010) Prosthetic hip joint infection with a Streptococcus agalactiae isolate not susceptible to penicillin G and ceftriaxone. J Antimicrob Chemother 65:594–595. https://doi.org/10.1093/jac/dkp458

    Article  PubMed  CAS  Google Scholar 

  13. Longtin J, Vermeiren C, Shahinas D, Tamber GS, McGeer A, Low DE, Katz K, Pillai DR (2011) Novel mutations in a patient isolate of Streptococcus agalactiae with reduced penicillin susceptibility emerging after long-term oral suppressive therapy. Antimicrob Agents Chemother 55:2983–2985. https://doi.org/10.1128/AAC.01243-10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Dahesh S, Hensler ME, Van Sorge NM, Gertz RE, Jr., Schrag S, Nizet V, Beall BW. (2008) Point mutation in the group B streptococcal pbp2x gene conferring decreased susceptibility to beta-lactam antibiotics. Antimicrob Agents Chemother 52:2915–2918. https://doi.org/10.1128/AAC.00461-08

  15. Kimura K, Nagano N, Nagano Y, Suzuki S, Wachino J, Shibayama K, Arakawa Y (2013) High frequency of fluoroquinolone- and macrolide-resistant streptococci among clinically isolated group B streptococci with reduced penicillin susceptibility. J Antimicrob Chemother 68:539–542. https://doi.org/10.1093/jac/dks423

    Article  PubMed  CAS  Google Scholar 

  16. Nagano N, Nagano Y, Toyama M, Kimura K, Tamura T, Shibayama K, Arakawa Y (2012) Nosocomial spread of multidrug-resistant group B streptococci with reduced penicillin susceptibility belonging to clonal complex 1. J Antimicrob Chemother 67:849–856. https://doi.org/10.1093/jac/dkr546

    Article  PubMed  CAS  Google Scholar 

  17. Nagano N, Nagano Y, Toyama M, Kimura K, Shibayama K, Arakawa Y (2014) Penicillin-susceptible group B streptococcal clinical isolates with reduced cephalosporin susceptibility. J Clin Microbiol 52:3406–3410. https://doi.org/10.1128/JCM.01291-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Clinical and Laboratory Standards Institute (2010) Performance standards for antimicrobial susceptibility testing, 20th ed. Clinical and Laboratory Standards Institute, Wayne, PA, p M100

    Google Scholar 

  19. Banno H, Kimura K, Tanaka Y, Sekizuka T, Kuroda M, Jin W, Wachino JI, Yamada K, Shibayama K, Arakawa Y (2017) Analysis of multidrug resistant group B streptococci with reduced penicillin susceptibility forming small, less hemolytic colonies. PLoS One 12:e0183453. https://doi.org/10.1371/journal.pone.0183453

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Hansen SM, Uldbjerg N, Kilian M, Sorensen UB (2004) Dynamics of Streptococcus agalactiae colonization in women during and after pregnancy and in their infants. J Clin Microbiol 42:83–89. https://doi.org/10.1128/JCM.42.1.83-89.2004

    Article  PubMed  PubMed Central  Google Scholar 

  21. Seki T, Kimura K, Reid ME, Miyazaki A, Banno H, Jin W, Wachino J, Yamada K, Arakawa Y (2015) High isolation rate of MDR group B streptococci with reduced penicillin susceptibility in Japan. J Antimicrob Chemother 70:2725–2728. https://doi.org/10.1093/jac/dkv203

    Article  PubMed  CAS  Google Scholar 

  22. Morozumi M, Wajima T, Takata M, Iwata S, Ubukata K (2016) Molecular characteristics of group B streptococci isolated from adults with invasive infections in Japan. J Clin Microbiol 54:2695–2700. https://doi.org/10.1128/JCM.01183-16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Metcalf BJ, Chochua S, Gertz RE Jr, Hawkins PA, Ricaldi J, Li Z, Walker H, Tran T, Rivers J, Mathis S, Jackson D, Glennen A, Lynfield R, McGee L, Beall B, Active Bacterial Core surveillance t (2017) Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA. Clin Microbiol Infect 23:574 e577–574 e514. https://doi.org/10.1016/j.cmi.2017.02.021

    Article  CAS  Google Scholar 

Download references

Acknowledgments

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.

Funding

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

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kouji Kimura.

Ethics declarations

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.

Electronic supplementary material

ESM 1

(DOCX 18 kb)

ESM 2

(DOCX 14 kb)

ESM 3

(DOCX 26 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Banno, H., Kimura, K., Seki, T. et al. High isolation rate and multidrug resistance tendency of penicillin-susceptible group B Streptococcus with reduced ceftibuten susceptibility in Japan. Eur J Clin Microbiol Infect Dis 37, 1511–1519 (2018). https://doi.org/10.1007/s10096-018-3278-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-018-3278-7

Keywords

Navigation