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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dc.contributor.author Tyrrell, Jonathan M.
dc.contributor.author Aboklaish, Ali F.
dc.contributor.author Walsh, Timothy R.
dc.contributor.author Vaara, Timo
dc.contributor.author Vaara, Martti
dc.date.accessioned 2020-03-31T02:31:24Z
dc.date.available 2021-12-18T03:46:00Z
dc.date.issued 2019-02
dc.identifier.citation 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
dc.identifier.other PURE: 132262487
dc.identifier.other PURE UUID: c0a9842a-b0e7-4497-9445-380e1ca9308d
dc.identifier.other WOS: 000456068800019
dc.identifier.uri http://hdl.handle.net/10138/313768
dc.description.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. en
dc.format.extent 5
dc.language.iso eng
dc.relation.ispartof Peptides
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Polymyxin B
dc.subject NAB739
dc.subject Klebsiella pneumoniae
dc.subject Escherichia coli
dc.subject Acinetobacter baumannii
dc.subject mcr-1
dc.subject Polymyxin resistance
dc.subject Rifampin
dc.subject Retapamulin
dc.subject Meropenem
dc.subject GRAM-NEGATIVE BACTERIA
dc.subject 3 POSITIVE CHARGES
dc.subject SUSCEPTIBILITY TESTING METHODS
dc.subject MECHANISMS
dc.subject AGENTS
dc.subject AGAR
dc.subject 3111 Biomedicine
dc.subject 1182 Biochemistry, cell and molecular biology
dc.title The polymyxin derivative NAB739 is synergistic with several antibiotics against polymyxin-resistant strains of Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii en
dc.type Article
dc.contributor.organization Department of Bacteriology and Immunology
dc.contributor.organization University of Helsinki
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1016/j.peptides.2018.12.006
dc.relation.issn 0196-9781
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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