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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
Capital Medical University, Peoples R China.
Capital Medical University, Peoples R China.
Capital Medical University, Peoples R China.
Capital Medical University, Peoples R China.
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2016 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, no 9, p. 5232-5237Article in journal (Refereed) Published
Abstract [en]

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 Lowenstein-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 Lowenstein-Jensen medium that was recently revised by the World Health Organization might be too high, resulting in the misclassification of phenotypically non-wildtype 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.

Place, publisher, year, edition, pages
AMER SOC MICROBIOLOGY , 2016. Vol. 60, no 9, p. 5232-5237
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Infectious Medicine
Identifiers
URN: urn:nbn:se:liu:diva-133538DOI: 10.1128/AAC.00393-16ISI: 000389055400017PubMedID: 27324769OAI: oai:DiVA.org:liu-133538DiVA, id: diva2:1060859
Note

Funding Agencies|Pacific Biosciences Inc.; Illumina Inc.; Hain Lifescience; Infectious Diseases Special Project, Minister of Health of China [2016ZX10003001-12]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201304]; Health Innovation Challenge Fund [HICF-T5-342, WT098600]; United Kingdom Department of Health; Wellcome Trust; Swedish Heart and Lung Foundation; Marianne and Marcus Wallenberg Foundation

Available from: 2016-12-30 Created: 2016-12-29 Last updated: 2017-11-29

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