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Title: In vitro activity and MIC of sitafloxacin against multidrug- resistant and extensively drug-resistant mycobacterium tuberculosis isolated in Thailand
Authors: Manoon Leechawengwongs
Therdsak Prammananan
Sarinya Jaitrong
Pamaree Billamas
Nampueng Makhao
Nongnard Thamnongdee
Arirat Thanormchat
Arisa Phurattanakornkul
Somcharn Rattanarangsee
Chate Ratanajaray
Areeya Disratthakit
Angkana Chaiprasert
Thailand National Center for Genetic Engineering and Biotechnology
Faculty of Medicine, Siriraj Hospital, Mahidol University
Vichaiyut Hospital
Siriraj Foundation
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2018
Citation: Antimicrobial Agents and Chemotherapy. Vol.62, No.1 (2018)
Abstract: Copyright © 2017 American Society for Microbiology. All Rights Reserved. New fluoroquinolones (FQs) have been shown to be more active against drug-resistant Mycobacterium tuberculosis strains than early FQs, such as ofloxacin. Sitafloxacin (STFX) is a new fluoroquinolone with in vitro activity against a broad range of bacteria, including M. tuberculosis. This study aimed to determine the in vitro activity of STFX against all groups of drug-resistant strains, including multidrug-resistant M. tuberculosis (MDR M. tuberculosis), MDR M. tuberculosis with quinolone resistance (pre-XDR), and extensively drug-resistant (XDR) strains. A total of 374 drug-resistant M. tuberculosis strains were tested for drug susceptibility by the conventional proportion method, and 95 strains were randomly submitted for MIC determination using the microplate alamarBlue assay (MABA). The results revealed that all the drug-resistant strains were susceptible to STFX at a critical concentration of 2 g/ml. Determination of the MIC90s of the strains showed different MIC levels; MDR M. tuberculosis strains had a MIC90 of 0.0625 g/ml, whereas pre-XDR and XDR M. tuberculosis strains had identical MIC90s of 0.5 g/ml. Common mutations within the quinolone resistance-determining region (QRDR) of gyrA and/or gyrB did not confer resistance to STFX, except that double mutations of GyrA at Ala90Val and Asp94Ala were found in strains with a MIC of 1.0 g/ml. The results indicated that STFX had potent in vitro activity against all the groups of drug-resistant M. tuberculosis strains and should be considered a new repurposed drug for treatment of multidrug-resistant and extensively drug-resistant TB.
ISSN: 10986596
Appears in Collections:Scopus 2018

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