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.

Abstract

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.

• Authors: Yoshifumi Ebara, Miyuki Morozumi, Mamiko Sato, Nobuko Moritoki, Meiwa Toyofuku, Misako Takata, Mitsuru Murata, Kimiko Ubukata, Satoshi Iwata
• Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (J Infect Chemother) Vol. 23 Issue 5 Pg. 312-318 (May 2017) ISSN: 1437-7780 [Electronic] Netherlands
• PMID: 28341517 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Gentamicins
• Penicillins
• beta-Lactams
• Ampicillin

Topics

• Ampicillin (pharmacology)
• Anti-Bacterial Agents (pharmacology)
• Gentamicins (pharmacology)
• Humans
• Microbial Sensitivity Tests (methods)
• Penicillins (pharmacology)
• Streptococcal Infections (drug therapy)
• Streptococcus agalactiae (drug effects)
• beta-Lactams (pharmacology)