Journal article

Octapeptin C4 Induces Less Resistance and Novel Mutations in an Epidemic Carbapenemase-producingKlebsiella pneumoniaeST258 Clinical Isolate Compared to Polymyxins

Miranda Pitt, Minh Duc Cao, Mark Butler, Soumya Ramu, Devika Ganesamoorthy, Mark Blaskovich, Lachlan Coin, Matthew Cooper

Published : 2018

Abstract

ABSTRACT Polymyxin B and E (colistin) have been pivotal in the treatment of extensively drug-resistant (XDR) Gram-negative bacterial infections, with increasing use over the past decade. Unfortunately, resistance to these antibiotics is rapidly emerging. The structurally-related octapeptin C4 (OctC4) has shown significant potency against XDR bacteria, including against polymyxin-resistant (Pmx-R) strains, but its mode of action remains undefined. We sought to compare and contrast the acquisition of XDR Klebsiella pneumoniae (ST258) resistance in vitro with all three lipopeptides to help elucidate the mode of action of the drugs and potential mechanisms of resistance evolution. Strikingly, 20..

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