Enhancement of bactericidal activity against group B streptococci with reduced penicillin susceptibility by uptake of gentamicin into cells resulting from combination with β-lactam antibiotics

Yoshifumi Ebara, Miyuki Morozumi, Mamiko Sato, Nobuko Moritoki, Meiwa Toyofuku, Misako Takata, Mitsuru Murata, Kimiko Ubukata, Satoshi Iwata

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Combined effects of penicillin (PEN) and gentamicin (GM) against Streptococcus agalactiae, i.e. group B streptococci (GBS), are known to occur, but synergy has not been examined in strains with reduced PEN susceptibility, usually called PEN-resistant GBS (PRGBS). We therefore studied combined effects of β-lactam antibiotics and GM in cultures of 3 PRGBS strains belonging to serotype Ia or III that were isolated from Japanese adults with invasive infections. Killing kinetics were determined at 2-h intervals from 0 to 6 h after exposure to ampicillin (AMP) or cefotaxime (CTX) combined with GM. Concentrations of GM in bacterial cells were measured by liquid chromatography-tandem mass spectrometry. Morphologic changes after exposure to agents were observed by transmission electron microscopy. Combining AMP or CTX with GM synergistically increased bactericidal activity against PRGBS beyond that of either β-lactam alone. GM concentrations in bacterial cells increased 5- to 8-fold when GM was combined with AMP or CTX. Electron microscopically, bacterial cells showed aggregates of strands and ribosomal damage most likely reflecting enhanced GM uptake into bacterial cells. This uptake appeared to result from cell wall damage caused by β-lactam antibiotics. This study suggests that combining β-lactam antibiotics with GM might be useful against severe PRGBS infection.

Original languageEnglish
Pages (from-to)312-318
Number of pages7
JournalJournal of Infection and Chemotherapy
Issue number5
Publication statusPublished - 2017 May 1



  • Antibiotic combinations
  • Bactericidal effect
  • Group B streptococci
  • Reduced penicillin susceptibility
  • Streptococcus agalactiae
  • Synergistic effect

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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