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Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e00096-16. doi: 10.1128/AAC.00096-16. Print 2017 Apr.

Influence of rhlR and lasR on Polymyxin Pharmacodynamics in Pseudomonas aeruginosa and Implications for Quorum Sensing Inhibition with Azithromycin.

Author information

1
Laboratory for Antimicrobial Pharmacodynamics, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York, USA.
2
New York State Center of Excellence in Life Sciences and Bioinformatics, Buffalo, New York, USA.
3
California Northstate University College of Pharmacy, Elk Grove, California, USA.
4
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida, USA.
5
Laboratory for Antimicrobial Pharmacodynamics, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York, USA btsuji@buffalo.edu.

Abstract

The impact of quorum sensing on polymyxin and azithromycin pharmacodynamics was assessed in Pseudomonas aeruginosa PAO1 and an isogenic rhlR/lasR double knockout. For polymyxin B, greater killing against the rhlR/lasR knockout than against PAO1 was observed at 108 CFU/ml (polymyxin B half-maximal effective concentration [EC50], 5.61 versus 12.5 mg/liter, respectively; P < 0.005). Polymyxin B combined with azithromycin (256 mg/liter) was synergistic against each strain, significantly reducing the respective polymyxin B EC50 compared to those with monotherapy (P < 0.005), and is a promising strategy by which to combat P. aeruginosa.

KEYWORDS:

P. aeruginosa; Pseudomonas aeruginosa; azithromycin; colistin; mechanism-based modeling; pharmacodynamics; polymyxin B; polymyxins; quorum sensing

PMID:
28096154
PMCID:
PMC5365695
DOI:
10.1128/AAC.00096-16
[Indexed for MEDLINE]
Free PMC Article

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