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Wild-Type and Non-Wild-Type Mycobacterium tuberculosis MIC Distributions for the Novel Fluoroquinolone Antofloxacin Compared with Those for Ofloxacin, Levofloxacin, and Moxifloxacin.

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Yu, Xia 
Wang, Guirong 
Chen, Suting 
Wei, Guomei 
Shang, Yuanyuan 


Antofloxacin (AFX) is a novel fluoroquinolone that has been approved in China for the treatment of infections caused by a variety of bacterial species. We investigated whether it could be repurposed for the treatment of tuberculosis by studying its in vitro activity. We determined the wild-type and non-wild-type MIC ranges for AFX as well as ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), using the microplate alamarBlue assay, of 126 clinical Mycobacterium tuberculosis strains from Beijing, China, of which 48 were OFX resistant on the basis of drug susceptibility testing on Löwenstein-Jensen medium. The MIC distributions were correlated with mutations in the quinolone resistance-determining regions of gyrA (Rv0006) and gyrB (Rv0005). Pharmacokinetic/pharmacodynamic (PK/PD) data for AFX were retrieved from the literature. AFX showed lower MIC levels than OFX but higher MIC levels than LFX and MFX on the basis of the tentative epidemiological cutoff values (ECOFFs) determined in this study. All strains with non-wild-type MICs for AFX harbored known resistance mutations that also resulted in non-wild-type MICs for LFX and MFX. Moreover, our data suggested that the current critical concentration of OFX for Löwenstein-Jensen medium that was recently revised by the World Health Organization might be too high, resulting in the misclassification of phenotypically non-wild-type strains with known resistance mutations as wild type. On the basis of our exploratory PK/PD calculations, the current dose of AFX is unlikely to be optimal for the treatment of tuberculosis, but higher doses could be effective.



Antitubercular Agents, China, DNA Gyrase, Drug Dosage Calculations, Drug Resistance, Bacterial, Fluoroquinolones, Gene Expression, Genotype, Humans, Levofloxacin, Microbial Sensitivity Tests, Moxifloxacin, Mutation, Mycobacterium tuberculosis, Ofloxacin, Tuberculosis, Pulmonary

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Antimicrob Agents Chemother

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American Society for Microbiology
Wellcome Trust (098600/Z/12/Z)
The work was supported by the research funding from Infectious Diseases Special Project, Minister of Health of China (2016ZX10003001-12) and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201304). The strains used in this project were obtained from the ‘Beijing Bio-Bank of clinical resources on Tuberculosis’ (D09050704640000), Beijing Chest Hospital. In addition, this study was supported by the Health Innovation Challenge Fund (HICF-T5-342 and WT098600), a parallel funding partnership between the UK Department of Health and Wellcome Trust. T. S. was supported by grants from the Swedish Heart and Lung Foundation and Marianne and Marcus Wallenberg Foundation. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health, Public Health England, or the Wellcome Trust. C. U. K. is a Junior Research Fellow at Wolfson College, Cambridge.