The polymyxin derivative NAB739 is synergistic with several antibiotics against polymyxin-resistant strains of Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii

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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
Other contributor: University of Helsinki, Department of Bacteriology and Immunology

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
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