当前位置： SCI文献检索 > JOURNAL OF MEDICAL MICROBIOLOGY期刊下所有文献 > Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa.

Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa.

Abstract：

:Introduction. Pseudomonas aeruginosa is an important Gram-negative pathogen that is intrinsically multidrug-resistant (MDR) and frequently associated with healthcare-associated outbreaks. With increasing resistance to antibiotics and with very few novel drugs under development, clinicians often use combinations to treat critically ill patients.Aim. The aim of this study was to evaluate the ability of epigallocatechin (EGCG) to restore the activity of aztreonam against clinical MDR strains of P. aeruginosa.Methodology. Checkerboard and time-kill kinetic assays were performed to assess synergy in vitro and the Galleria mellonella model of infection was used to test the efficacy of the combination in vivo. Accumulation assays were performed to gain insight into the mechanism of action.Results. The results demonstrate that synergy between aztreonam and EGCG exists [fractional inhibitory concentration indices (FICIs) 0.02-0.5], with the combination affording significantly (P=<0.05) enhanced bacterial killing, with a >3 log10 reduction in colony-forming units ml-1 at 24 h. EGCG was able to restore susceptibility to aztreonam to a level equal to or below the breakpoint set by the European Committee for Antimicrobial Susceptibility Testing. In G. mellonella, the combination was superior to monotherapy, with increased larval survival observed (94 % vs ≤63 %). We also demonstrated the relatively low toxicity of EGCG to human keratinocytes and G. mellonella larvae. Accumulation assay data suggest that the mechanism of synergy may be due to EGCG increasing the uptake of aztreonam.Conclusion. EGCG was able to restore the activity of aztreonam against MDR P. aeruginosa. The data presented support further evaluation of the aztreonam-EGCG combination and highlight its potential for use in clinical medicine.

journal_name

J Med Microbiol

journal_title

Journal of medical microbiology

authors

Betts JW,Hornsey M,Higgins PG,Lucassen K,Wille J,Salguero FJ,Seifert H,La Ragione RM

doi

10.1099/jmm.0.001060

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

1552-1559

issue

eissn

0022-2615

issn

1473-5644

journal_volume

pub_type

杂志文章

在线工具

Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa.