Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant In this study, we compared the activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-r...

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Veröffentlicht in:Antimicrobial agents and chemotherapy 2018-08, Vol.62 (8)
Hauptverfasser: Zong, Zhaojing, Jing, Wei, Shi, Jin, Wen, Shu'an, Zhang, Tingting, Huo, Fengmin, Shang, Yuanyuan, Liang, Qian, Huang, Hairong, Pang, Yu
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container_issue 8
container_start_page
container_title Antimicrobial agents and chemotherapy
container_volume 62
creator Zong, Zhaojing
Jing, Wei
Shi, Jin
Wen, Shu'an
Zhang, Tingting
Huo, Fengmin
Shang, Yuanyuan
Liang, Qian
Huang, Hairong
Pang, Yu
description Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant In this study, we compared the activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, , and genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC values for isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates ( > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group ( = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within that endowed with linezolid, but not delpazolid, resistance was identified.
doi_str_mv 10.1128/AAC.00165-18
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Additionally, genetic mutations in 23S rRNA, , and genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC values for isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates ( &gt; 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group ( = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by that contributed to high-level resistance to linezolid (MIC of &gt;16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. 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Additionally, genetic mutations in 23S rRNA, , and genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC values for isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates ( &gt; 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group ( = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by that contributed to high-level resistance to linezolid (MIC of &gt;16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within that endowed with linezolid, but not delpazolid, resistance was identified.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>29844043</pmid><doi>10.1128/AAC.00165-18</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-6803-9807</orcidid><oa>free_for_read</oa></addata></record>
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subjects Antitubercular Agents
Drug Resistance, Multiple, Bacterial
Gene Expression Regulation, Bacterial
Genes, Bacterial
Linezolid
Mycobacterium tuberculosis
Oxazolidinones
Susceptibility
title Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China
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