Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of.
J Med Microbiol. 2019 Aug 16. Epub 2019 Aug 16. PMID: 31419210
Jonathan W Betts
.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.. The aim of this study was to evaluate the ability of epigallocatechin (EGCG) to restore the activity of aztreonam against clinical MDR strains of.. Checkerboard and time-kill kinetic assays were performed to assess synergyand themodel of infection was used to test the efficacy of the combination. Accumulation assays were performed to gain insight into the mechanism of action.. The results demonstrate that synergy between aztreonam and EGCG exists [fractional inhibitory concentration indices (FICIs) 0.02-0.5], with the combination affording significantly (=<0.05) enhanced bacterial killing, with a>3 logreduction in colony-forming units mlat 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, 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 andlarvae. Accumulation assay data suggest that the mechanism of synergy may be due to EGCG increasing the uptake of aztreonam.. EGCG was able to restore the activity of aztreonam against MDR. The data presented support further evaluation of the aztreonam-EGCG combination and highlight its potential for use in clinical medicine.