Clinical and genomic insights into persistent carbapenem-resistant Klebsiella pneumoniae bacteremia: risk factors, resistance mechanisms, and treatment challenges.

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal Pub Date : 2025-08-18 DOI:10.1016/j.bj.2025.100905

Shian-Sen Shie, Ya-Han Yang, Yin-Hsiang Kung, Chih-Jung Chen

{"title":"Clinical and genomic insights into persistent carbapenem-resistant Klebsiella pneumoniae bacteremia: risk factors, resistance mechanisms, and treatment challenges.","authors":"Shian-Sen Shie, Ya-Han Yang, Yin-Hsiang Kung, Chih-Jung Chen","doi":"10.1016/j.bj.2025.100905","DOIUrl":null,"url":null,"abstract":"Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major cause of nosocomial infections with high mortality rates. Persistent bacteremia, indicative of treatment failure, poses significant clinical challenges. This study aimed to identify clinical parameters for persistent CRKP bacteremia while exploring microbial and genetic characteristics.Materials and methods: A case-control study was conducted on patients with CRKP bacteremia from January 2016 to July 2019 at a tertiary hospital in Taiwan. Clinical, demographic, and microbiological data were collected for 61 cases of persistent bacteremia and 122 matched controls without persistent infections. Conditional logistic regression was used to evaluate risk factors for persistent bacteremia. Whole-genome sequencing (WGS) was used to identify genotypes and factors mediating resistance and virulence in the strains.Results: Persistent CRKP bacteremia was independently associated with mechanical ventilation (adjusted odds ratio [aOR] 11.007, 95% confidence interval [CI] 2.137-56.693), a lower Pitt bacteremia score (aOR 0.642, 95% CI 0.494-0.835), and the use of colistin (aOR 11.18, 95% CI 2.988-41.787) and tigecycline (aOR 16.42, 95% 4.495-60.0) in definitive therapy. Strains from either group shared similar capsular types. WGS identified three dominant multidrug-resistant clones, ST11, ST307, and ST15, harboring carbapenemase and virulence factors encoding yersiniabactin. A strain of hypervirulent clone ST23 exhibited high virulence but lacked carbapenemase genes, suggesting alternative resistance mechanisms of CR phenotype.Conclusions: Antimicrobial regimens with tigecycline and colistin were insufficient for effectively managing CRKP bacteremia. The convergence of resistance and virulence in prevalent clones demands the urgent introduction of novel therapeutics. Aggressive and tailored strategies are critical for improving outcomes in high-risk patients.","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100905"},"PeriodicalIF":4.4000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.bj.2025.100905","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major cause of nosocomial infections with high mortality rates. Persistent bacteremia, indicative of treatment failure, poses significant clinical challenges. This study aimed to identify clinical parameters for persistent CRKP bacteremia while exploring microbial and genetic characteristics.

Materials and methods: A case-control study was conducted on patients with CRKP bacteremia from January 2016 to July 2019 at a tertiary hospital in Taiwan. Clinical, demographic, and microbiological data were collected for 61 cases of persistent bacteremia and 122 matched controls without persistent infections. Conditional logistic regression was used to evaluate risk factors for persistent bacteremia. Whole-genome sequencing (WGS) was used to identify genotypes and factors mediating resistance and virulence in the strains.

Results: Persistent CRKP bacteremia was independently associated with mechanical ventilation (adjusted odds ratio [aOR] 11.007, 95% confidence interval [CI] 2.137-56.693), a lower Pitt bacteremia score (aOR 0.642, 95% CI 0.494-0.835), and the use of colistin (aOR 11.18, 95% CI 2.988-41.787) and tigecycline (aOR 16.42, 95% 4.495-60.0) in definitive therapy. Strains from either group shared similar capsular types. WGS identified three dominant multidrug-resistant clones, ST11, ST307, and ST15, harboring carbapenemase and virulence factors encoding yersiniabactin. A strain of hypervirulent clone ST23 exhibited high virulence but lacked carbapenemase genes, suggesting alternative resistance mechanisms of CR phenotype.

Conclusions: Antimicrobial regimens with tigecycline and colistin were insufficient for effectively managing CRKP bacteremia. The convergence of resistance and virulence in prevalent clones demands the urgent introduction of novel therapeutics. Aggressive and tailored strategies are critical for improving outcomes in high-risk patients.

查看原文本刊更多论文

持久性耐碳青霉烯肺炎克雷伯菌菌血症的临床和基因组研究：危险因素、耐药机制和治疗挑战。

碳青霉烯耐药肺炎克雷伯菌（CRKP）是医院感染的主要原因，死亡率高。持续菌血症是治疗失败的标志，对临床提出了重大挑战。本研究旨在确定持续性CRKP菌血症的临床参数，同时探索微生物和遗传特征。材料与方法：对台湾某三级医院2016年1月至2019年7月的CRKP菌血症患者进行病例对照研究。收集了61例持续性菌血症和122例无持续性感染的匹配对照的临床、人口统计学和微生物学数据。采用条件logistic回归评价持续性菌血症的危险因素。采用全基因组测序（WGS）鉴定菌株的基因型和介导抗性和毒力的因素。结果：持续性CRKP菌血症与机械通气（调整优势比[aOR] 11.007, 95%可信区间[CI] 2.137-56.693）、较低的Pitt菌血症评分（aOR 0.642, 95% CI 0.494-0.835）以及在最终治疗中使用粘菌素（aOR 11.18, 95% CI 2.988-41.787）和替加环素（aOR 16.42, 95% 4.495-60.0）独立相关。两组菌株的荚膜类型相似。WGS鉴定出3个主要的多药耐药克隆，ST11、ST307和ST15，它们含有碳青霉烯酶和编码耶尔希菌abactin的毒力因子。一株高毒力克隆ST23表现出高毒力，但缺乏碳青霉烯酶基因，提示CR表型的其他抗性机制。结论：替加环素和粘菌素的抗菌方案不足以有效管理CRKP菌血症。在流行的克隆中，耐药性和毒力的趋同要求迫切引入新的治疗方法。积极和量身定制的策略对于改善高危患者的预后至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biomedical Journal Medicine-General Medicine

CiteScore

11.60

自引率

1.80%

发文量

128

审稿时长

42 days

期刊介绍： Biomedical Journal publishes 6 peer-reviewed issues per year in all fields of clinical and biomedical sciences for an internationally diverse authorship. Unlike most open access journals, which are free to readers but not authors, Biomedical Journal does not charge for subscription, submission, processing or publication of manuscripts, nor for color reproduction of photographs. Clinical studies, accounts of clinical trials, biomarker studies, and characterization of human pathogens are within the scope of the journal, as well as basic studies in model species such as Escherichia coli, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealing the function of molecules, cells, and tissues relevant for human health. However, articles on other species can be published if they contribute to our understanding of basic mechanisms of biology. A highly-cited international editorial board assures timely publication of manuscripts. Reviews on recent progress in biomedical sciences are commissioned by the editors.