Tyrrell , J M , Aboklaish , A F , Walsh , T R , Vaara , T & Vaara , M 2019 , ' The polymyxin derivative NAB739 is synergistic with several antibiotics against polymyxin-resistant strains of Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii ' , Peptides , vol. 112 , pp. 149-153 . https://doi.org/10.1016/j.peptides.2018.12.006
Title: | The polymyxin derivative NAB739 is synergistic with several antibiotics against polymyxin-resistant strains of Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii |
Author: | Tyrrell, Jonathan M.; Aboklaish, Ali F.; Walsh, Timothy R.; Vaara, Timo; Vaara, Martti |
Contributor organization: | Department of Bacteriology and Immunology University of Helsinki |
Date: | 2019-02 |
Language: | eng |
Number of pages: | 5 |
Belongs to series: | Peptides |
ISSN: | 0196-9781 |
DOI: | https://doi.org/10.1016/j.peptides.2018.12.006 |
URI: | http://hdl.handle.net/10138/313768 |
Abstract: | The antibiotic crisis has reinstated polymyxins, once abandoned because of their toxicity. Now, preclinical studies have revealed better tolerated and more effective derivatives of polymyxins such as NAB739. Simultaneously, polymyxin-resistant (PMR) strains such as the mcr-1 strains have received lots of justified publicity, even though they are still very rare. Here we show that NAB739 sensitizes the PMR strains to rifampin, a classic "anti-Gram-positive" antibiotic excluded by the intact outer membrane (OM) permeability barrier, as well as to retapamulin, the surrogate of lefamulin, an antibiotic under development against Gram-positive bacteria. Polymyxin B was used as a comparator. The combination of NAB739 and rifampin was synergistic against ten out of eleven PMR strains of Escherichia coll. (Fractional Synergy Indices, FICs, 0.14-0.19) and that of NAB739 and retapamulin against all the tested eleven strains (FICs 0.19-0.25). Against PMR Klebsiella pneumoniae (n = 7), the FICs were 0.13-0.27 for NAB739 + rifampin and 0.14-0.28 for NAB739 + retapamulin. Against Acinetobacter baumannii (n = 2), the combination of NAB739 and rifampin had the FIC of 0.09-0.19. Furthermore, NAB739 and meropenem were synergistic (FICs 0.25-0.50) against four out of five PMR strains that were simultaneously resistant to meropenem. |
Subject: |
Polymyxin B
NAB739 Klebsiella pneumoniae Escherichia coli Acinetobacter baumannii mcr-1 Polymyxin resistance Rifampin Retapamulin Meropenem GRAM-NEGATIVE BACTERIA 3 POSITIVE CHARGES SUSCEPTIBILITY TESTING METHODS MECHANISMS AGENTS AGAR 3111 Biomedicine 1182 Biochemistry, cell and molecular biology |
Peer reviewed: | Yes |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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