Universität zu Köln

Betts, Jonathan W., Hornsey, Michael ORCID: 0000-0001-8990-2059, Higgins, Paul G. ORCID: 0000-0001-8677-9454, Lucassen, Kai ORCID: 0000-0002-6335-7731, Wille, Julia, Salguero, Francisco J., Seifert, Harald and La Ragione, Roberto M. (2019). Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa. J. Med. Microbiol., 68 (10). S. 1552 - 1560. LONDON: MICROBIOLOGY SOC. ISSN 1473-5644

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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 log(10) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Betts, Jonathan W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hornsey, Michael UNSPECIFIED orcid.org/0000-0001-8990-2059 UNSPECIFIED Higgins, Paul G. UNSPECIFIED orcid.org/0000-0001-8677-9454 UNSPECIFIED Lucassen, Kai UNSPECIFIED orcid.org/0000-0002-6335-7731 UNSPECIFIED Wille, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Salguero, Francisco J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Seifert, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED La Ragione, Roberto M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-132755
DOI:	10.1099/jmm.0.001060
Journal or Publication Title:	J. Med. Microbiol.
Volume:	68
Number:	10
Page Range:	S. 1552 - 1560
Date:	2019
Publisher:	MICROBIOLOGY SOC
Place of Publication:	LONDON
ISSN:	1473-5644
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GALLERIA-MELLONELLA; ANTIBACTERIAL ACTIVITY; BETA-LACTAMS; COMBINATION; MECHANISM; COLISTIN; MODEL Multiple languages Microbiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13275