Ghady Haidar, Ellen G Kline, Georgios D Kitsios, Xiaohong Wang, Eun Jeong Kwak, Anthony Newbrough, Kelly Friday, Kailey Hughes Kramer, Ryan K Shields
{"title":"对一株产生 NDM 的大肠埃希菌血流分离菌株进行治疗后，发现其对阿曲南类-阿维菌素和头孢羟氨苄的耐药性较高。","authors":"Ghady Haidar, Ellen G Kline, Georgios D Kitsios, Xiaohong Wang, Eun Jeong Kwak, Anthony Newbrough, Kelly Friday, Kailey Hughes Kramer, Ryan K Shields","doi":"10.1093/jacamr/dlae141","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cefiderocol (FDC) or ceftazidime-avibactam with aztreonam (CZA-ATM) are frontline agents for New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales; however, clinical data are scarce, and mechanisms of treatment-emergent resistance are ill-defined. Our objectives were to characterize serial isolates and stool microbiota from a liver transplant recipient with NDM-producing <i>Escherichia coli</i> bacteraemia.</p><p><strong>Methods: </strong>Isolates collected pre- and post-CZA-ATM treatment underwent broth microdilution susceptibility testing and whole-genome sequencing. Longitudinal stool collected during CZA-ATM therapy underwent metagenomic sequencing (Nanopore MinION).</p><p><strong>Results: </strong>The baseline isolate exhibited elevated MICs for ATM-AVI (16/4 µg/mL) and FDC (8 µg/mL). Posttreatment, a rectal surveillance isolate exhibited high-level resistance to ATM-AVI (> 128/4 µg/mL) and FDC (32 µg/mL). Both isolates belonged to ST361 and harboured WT <i>bla</i> <sub>NDM-5</sub>. The baseline isolate contained wild type (WT) <i>bla</i> <sub>CMY-145</sub> and mutations in <i>ftsI</i> (which encodes PBP3), including a YRIN insertion at residue 338 and the non-synonymous substitutions Q227H, E353K and I536L. The posttreatment isolate harboured new mutations in <i>ftsI</i> (A417 V) and <i>bla</i> <sub>CMY-145</sub> (L139R and N366Y). Analysis of four stool samples collected during CZA-ATM treatment revealed high <i>E. coli</i> abundance. <i>E. coli</i> relative abundance increased from 34.5% (first sample) to 61.9% (last sample).</p><p><strong>Conclusions: </strong>Baseline mutations in <i>ftsI</i> were associated with reduced susceptibility to ATM-AVI and FDC in an ST361 NDM-5-producing <i>E. coli</i> bloodstream isolate. High-level resistance was selected after CZA-ATM treatment, resulting in new <i>ftsl</i> and <i>bla</i> <sub>CMY-145</sub> mutations. These findings underscore the need for ATM-AVI susceptibility testing for NDM producers, and the potential for PBP3 mutations to confer cross-resistance to ATM-AVI and FDC, which can emerge after CZA-ATM treatment.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 5","pages":"dlae141"},"PeriodicalIF":3.7000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375572/pdf/","citationCount":"0","resultStr":"{\"title\":\"Emergence of high-level aztreonam-avibactam and cefiderocol resistance following treatment of an NDM-producing <i>Escherichia coli</i> bloodstream isolate exhibiting reduced susceptibility to both agents at baseline.\",\"authors\":\"Ghady Haidar, Ellen G Kline, Georgios D Kitsios, Xiaohong Wang, Eun Jeong Kwak, Anthony Newbrough, Kelly Friday, Kailey Hughes Kramer, Ryan K Shields\",\"doi\":\"10.1093/jacamr/dlae141\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cefiderocol (FDC) or ceftazidime-avibactam with aztreonam (CZA-ATM) are frontline agents for New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales; however, clinical data are scarce, and mechanisms of treatment-emergent resistance are ill-defined. Our objectives were to characterize serial isolates and stool microbiota from a liver transplant recipient with NDM-producing <i>Escherichia coli</i> bacteraemia.</p><p><strong>Methods: </strong>Isolates collected pre- and post-CZA-ATM treatment underwent broth microdilution susceptibility testing and whole-genome sequencing. Longitudinal stool collected during CZA-ATM therapy underwent metagenomic sequencing (Nanopore MinION).</p><p><strong>Results: </strong>The baseline isolate exhibited elevated MICs for ATM-AVI (16/4 µg/mL) and FDC (8 µg/mL). Posttreatment, a rectal surveillance isolate exhibited high-level resistance to ATM-AVI (> 128/4 µg/mL) and FDC (32 µg/mL). Both isolates belonged to ST361 and harboured WT <i>bla</i> <sub>NDM-5</sub>. The baseline isolate contained wild type (WT) <i>bla</i> <sub>CMY-145</sub> and mutations in <i>ftsI</i> (which encodes PBP3), including a YRIN insertion at residue 338 and the non-synonymous substitutions Q227H, E353K and I536L. The posttreatment isolate harboured new mutations in <i>ftsI</i> (A417 V) and <i>bla</i> <sub>CMY-145</sub> (L139R and N366Y). Analysis of four stool samples collected during CZA-ATM treatment revealed high <i>E. coli</i> abundance. <i>E. coli</i> relative abundance increased from 34.5% (first sample) to 61.9% (last sample).</p><p><strong>Conclusions: </strong>Baseline mutations in <i>ftsI</i> were associated with reduced susceptibility to ATM-AVI and FDC in an ST361 NDM-5-producing <i>E. coli</i> bloodstream isolate. High-level resistance was selected after CZA-ATM treatment, resulting in new <i>ftsl</i> and <i>bla</i> <sub>CMY-145</sub> mutations. These findings underscore the need for ATM-AVI susceptibility testing for NDM producers, and the potential for PBP3 mutations to confer cross-resistance to ATM-AVI and FDC, which can emerge after CZA-ATM treatment.</p>\",\"PeriodicalId\":14594,\"journal\":{\"name\":\"JAC-Antimicrobial Resistance\",\"volume\":\"6 5\",\"pages\":\"dlae141\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375572/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JAC-Antimicrobial Resistance\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/jacamr/dlae141\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAC-Antimicrobial Resistance","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jacamr/dlae141","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Emergence of high-level aztreonam-avibactam and cefiderocol resistance following treatment of an NDM-producing Escherichia coli bloodstream isolate exhibiting reduced susceptibility to both agents at baseline.
Background: Cefiderocol (FDC) or ceftazidime-avibactam with aztreonam (CZA-ATM) are frontline agents for New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales; however, clinical data are scarce, and mechanisms of treatment-emergent resistance are ill-defined. Our objectives were to characterize serial isolates and stool microbiota from a liver transplant recipient with NDM-producing Escherichia coli bacteraemia.
Methods: Isolates collected pre- and post-CZA-ATM treatment underwent broth microdilution susceptibility testing and whole-genome sequencing. Longitudinal stool collected during CZA-ATM therapy underwent metagenomic sequencing (Nanopore MinION).
Results: The baseline isolate exhibited elevated MICs for ATM-AVI (16/4 µg/mL) and FDC (8 µg/mL). Posttreatment, a rectal surveillance isolate exhibited high-level resistance to ATM-AVI (> 128/4 µg/mL) and FDC (32 µg/mL). Both isolates belonged to ST361 and harboured WT blaNDM-5. The baseline isolate contained wild type (WT) blaCMY-145 and mutations in ftsI (which encodes PBP3), including a YRIN insertion at residue 338 and the non-synonymous substitutions Q227H, E353K and I536L. The posttreatment isolate harboured new mutations in ftsI (A417 V) and blaCMY-145 (L139R and N366Y). Analysis of four stool samples collected during CZA-ATM treatment revealed high E. coli abundance. E. coli relative abundance increased from 34.5% (first sample) to 61.9% (last sample).
Conclusions: Baseline mutations in ftsI were associated with reduced susceptibility to ATM-AVI and FDC in an ST361 NDM-5-producing E. coli bloodstream isolate. High-level resistance was selected after CZA-ATM treatment, resulting in new ftsl and blaCMY-145 mutations. These findings underscore the need for ATM-AVI susceptibility testing for NDM producers, and the potential for PBP3 mutations to confer cross-resistance to ATM-AVI and FDC, which can emerge after CZA-ATM treatment.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
