Fluopsin C for Treating Multidrug-Resistant Infections: In vitro Activity Against Clinically Important Strains and in vivo Efficacy Against Carbapenemase-Producing Klebsiella pneumoniae

The increasing emergence of multidrug-resistant (MDR) organisms in hospital infections is causing a global public health crisis. The development of drugs with effective antibiotic action against such agents is of the highest priority. In the present study, the action of Fluopsin C against MDR clinic...

Full description

Saved in:

Bibliographic Details
Published in:	Frontiers in microbiology Vol. 10; p. 2431
Main Authors:	Navarro, Miguel Octavio Pérez, Simionato, Ane Stefano, Pérez, Juan Carlos Bedoya, Barazetti, André Riedi, Emiliano, Janaina, Niekawa, Erika Tyemi Goya, Andreata, Matheus Felipe de Lima, Modolon, Fluvio, Dealis, Mickely Liuti, Araújo, Eduardo José de Almeida, Carlos, Thalita Massi, Scarpelim, Odair José, da Silva, Denise Brentan, Chryssafidis, Andreas Lazaros, Bruheim, Per, Andrade, Galdino
Format:	Journal Article
Language:	English
Published:	Frontiers Media S.A 25-10-2019
Subjects:	antibiotic electronic microscopy histopathology metalloantibiotic Microbiology murine sepsis model resistant mutant
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The increasing emergence of multidrug-resistant (MDR) organisms in hospital infections is causing a global public health crisis. The development of drugs with effective antibiotic action against such agents is of the highest priority. In the present study, the action of Fluopsin C against MDR clinical isolates was evaluated under in vitro and in vivo conditions. Fluopsin C was produced in cell suspension culture of Pseudomonas aeruginosa LV strain, purified by liquid adsorption chromatography and identified by mass spectrometric analysis. Bioactivity, bacterial resistance development risk against clinically important pathogenic strains and toxicity in mammalian cell were initially determined by in vitro models. In vivo toxicity was evaluated in Tenebrio molitor larvae and mice. The therapeutic efficacy of intravenous Fluopsin C administration was evaluated in a murine model of Klebsiella pneumoniae (KPC) acute sepsis, using six different treatments. The in vitro results indicated MIC and MBC below 2 μg/mL and low bacterial resistance development frequency. Electron microscopy showed that Fluopsin C may have altered the exopolysaccharide matrix and caused disruption of the cell wall of MDR bacteria. Best therapeutic results were achieved in mice treated with a single dose of 2 mg/kg and in mice treated with two doses of 1 mg/kg, 8 h apart. Furthermore, acute and chronic histopathological studies demonstrated absent nephrotoxicity and moderate hepatotoxicity. The results demonstrated the efficacy of Fluopsin C against MDR organisms in in vitro and in vivo models, and hence it can be a novel therapeutic agent for the control of severe MDR infections.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Divakar Sharma, Indian Institute of Technology Delhi, India; Maurizio Sanguinetti, Catholic University of the Sacred Heart, Italy Edited by: Ana R. Freitas, University of Porto, Portugal This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology
ISSN:	1664-302X 1664-302X
DOI:	10.3389/fmicb.2019.02431