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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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 |
format | Article |
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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.</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.00165-18</identifier><identifier>PMID: 29844043</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Antitubercular Agents ; Drug Resistance, Multiple, Bacterial ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Linezolid ; Mycobacterium tuberculosis ; Oxazolidinones ; Susceptibility</subject><ispartof>Antimicrobial agents and chemotherapy, 2018-08, Vol.62 (8)</ispartof><rights>Copyright © 2018 American Society for Microbiology.</rights><rights>Copyright © 2018 American Society for Microbiology. 2018 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a3338-400291e100e973113a149cbca8c6bab1af9e90e4140c2b5944baf54cf0371d693</citedby><cites>FETCH-LOGICAL-a3338-400291e100e973113a149cbca8c6bab1af9e90e4140c2b5944baf54cf0371d693</cites><orcidid>0000-0001-6803-9807</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105784/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105784/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29844043$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zong, Zhaojing</creatorcontrib><creatorcontrib>Jing, Wei</creatorcontrib><creatorcontrib>Shi, Jin</creatorcontrib><creatorcontrib>Wen, Shu'an</creatorcontrib><creatorcontrib>Zhang, Tingting</creatorcontrib><creatorcontrib>Huo, Fengmin</creatorcontrib><creatorcontrib>Shang, Yuanyuan</creatorcontrib><creatorcontrib>Liang, Qian</creatorcontrib><creatorcontrib>Huang, Hairong</creatorcontrib><creatorcontrib>Pang, Yu</creatorcontrib><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</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><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.</description><subject>Antitubercular Agents</subject><subject>Drug Resistance, Multiple, Bacterial</subject><subject>Gene Expression Regulation, Bacterial</subject><subject>Genes, Bacterial</subject><subject>Linezolid</subject><subject>Mycobacterium tuberculosis</subject><subject>Oxazolidinones</subject><subject>Susceptibility</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kk9v0zAYhyMEYmVw44x8BIkMO3HS-IJUpRtUapmEgKtlO29aT4nd-U9Z9x35Tpi2TOzAyfrpffRYfv3LstcEXxBSNB9ms_YCY1JXOWmeZBOCWZPXFaufZhOM6zqnDaZn2Qvvb3DKFcPPs7OCNZRiWk6yX60dt8Jpbw2yPVoY9EMHZ9FMBb3TYY-E6dBq0aK59sFpGYO2xiMJ4SeAQWED6IvdwYCu78S9HXSnjTWA5jBsj_kgWGoDp7QW2viAVnEIunNxnX8Fn9TChAN5eRfAeJ2MezR_PF7tlZVCBXA6jihECU7FwaYx0ga1G23Ey-xZLwYPr07nefb96vJb-zlfXn9atLNlLsqybHKKccEIEIyBTUtCSkEoU1KJRtVSSCJ6BgwDJRSrQlaMUin6iqoel1PS1aw8zz4evdsoR-gUmODEwLdOj8LtuRWaP54YveFru-M1wdW0oUnw9iRw9jaCD3zUXsEwCAM2el5gOi3Sz9Ukoe-PqHLWewf9wzUE8z8N4KkB_NAATpqEvzviwo8Fv7HRmbSJ_7Fv_n3Gg_hvPcrfNhO-ew</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Zong, Zhaojing</creator><creator>Jing, Wei</creator><creator>Shi, Jin</creator><creator>Wen, Shu'an</creator><creator>Zhang, Tingting</creator><creator>Huo, Fengmin</creator><creator>Shang, Yuanyuan</creator><creator>Liang, Qian</creator><creator>Huang, Hairong</creator><creator>Pang, Yu</creator><general>American Society for Microbiology</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6803-9807</orcidid></search><sort><creationdate>20180801</creationdate><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</title><author>Zong, Zhaojing ; Jing, Wei ; Shi, Jin ; Wen, Shu'an ; Zhang, Tingting ; Huo, Fengmin ; Shang, Yuanyuan ; Liang, Qian ; Huang, Hairong ; Pang, Yu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a3338-400291e100e973113a149cbca8c6bab1af9e90e4140c2b5944baf54cf0371d693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Antitubercular Agents</topic><topic>Drug Resistance, Multiple, Bacterial</topic><topic>Gene Expression Regulation, Bacterial</topic><topic>Genes, Bacterial</topic><topic>Linezolid</topic><topic>Mycobacterium tuberculosis</topic><topic>Oxazolidinones</topic><topic>Susceptibility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zong, Zhaojing</creatorcontrib><creatorcontrib>Jing, Wei</creatorcontrib><creatorcontrib>Shi, Jin</creatorcontrib><creatorcontrib>Wen, Shu'an</creatorcontrib><creatorcontrib>Zhang, Tingting</creatorcontrib><creatorcontrib>Huo, Fengmin</creatorcontrib><creatorcontrib>Shang, Yuanyuan</creatorcontrib><creatorcontrib>Liang, Qian</creatorcontrib><creatorcontrib>Huang, Hairong</creatorcontrib><creatorcontrib>Pang, Yu</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zong, Zhaojing</au><au>Jing, Wei</au><au>Shi, Jin</au><au>Wen, Shu'an</au><au>Zhang, Tingting</au><au>Huo, Fengmin</au><au>Shang, Yuanyuan</au><au>Liang, Qian</au><au>Huang, Hairong</au><au>Pang, Yu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2018-08-01</date><risdate>2018</risdate><volume>62</volume><issue>8</issue><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>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.</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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