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回顾性分析耐碳青霉烯类肺炎克雷伯菌血流感染的分子特征、危险因素和转归。

Retrospective analysis of molecular characteristics, risk factors, and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections.

机构信息

Department of Basic Medical Laboratory, The 980th Hospital of the PLA Joint Logistical Support Force (Bethune International Peace Hospital), Shijiazhuang, 050081, China.

Department of Outpatient, The 980th Hospital of the PLA Joint Logistical Support Force (Bethune International Peace Hospital), Shijiazhuang, 050081, China.

出版信息

BMC Microbiol. 2024 Aug 22;24(1):309. doi: 10.1186/s12866-024-03465-4.

Abstract

BACKGROUND

Klebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis.

RESULTS

Our study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357-61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312-16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119-11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226-2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922-23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with bla as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU.

CONCLUSIONS

The analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians' understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes.

摘要

背景

肺炎克雷伯菌(KP)是导致血流感染(BSI)的第二大常见革兰氏阴性菌。近年来,由于耐碳青霉烯类肺炎克雷伯菌(CRKP)的出现,BSI 的治疗变得越来越复杂。尽管许多研究已经探讨了 CRKP-BSI 发展的危险因素、KP-BSI 患者的死亡率以及 CRKP 的分子流行病学特征,但不同人群、国家和医院的数据差异导致结论不一致。在这项单中心回顾性观察性研究中,我们利用逻辑回归分析确定了 CRKP-BSI 的独立危险因素以及与 KP-BSI 患者死亡率相关的因素。此外,还开发了基于风险因素的预测模型。对 CRKP 分离株进行全基因组测序(WGS),然后评估微生物学特征,包括抗生素耐药性和毒力基因,以及流行病学特征和系统发育分析。

结果

我们的研究共纳入了 134 例 KP-BSI 患者,其中 50 例感染了 CRKP,84 例感染了碳青霉烯类敏感肺炎克雷伯菌(CSKP)。CRKP-BSI 的独立危险因素包括胃管插入(OR=9.143;CI=1.357-61.618;P=0.023)、重症监护病房(ICU)住院史(OR=4.642;CI=1.312-16.422;P=0.017)和非血液部位检出 CRKP(OR=8.112;CI=2.130-30.894;P=0.002)。多变量分析显示,6 天后微生物学清除(OR=3.569;CI=1.119-11.387;P=0.032)、高 Pitt 菌血症评分(OR=1.609;CI=1.226-2.111;P=0.001)和 BSI 后经验性治疗不当(OR=6.756;CI=1.922-23.753;P=0.003)是 KP-BSI 28 天死亡率的独立危险因素。预测模型证实,6.5 天后微生物学清除和 Pitt 菌血症评分 4.5 分或更高是 28 天死亡率的显著预测指标。生物信息学分析发现 ST11 是 CRKP 的主要序列类型,bla 是最常见的基因变体。CRKP 菌株携带多种质粒介导的耐药基因和一些毒力基因。系统发育分析表明 ICU 内存在 ST11 CRKP 的医院内传播。

结论

分析 CRKP-BSI 发展的危险因素以及 KP-BSI 与 28 天死亡率之间的关系,以及基于风险因素的预测模型的开发和 CRKP 菌株的特征分析,提高了临床医生对导致 BSI 的病原体的认识。这种认识可能有助于及时对疑似 KP-BSI 患者进行抗生素治疗,从而改善治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9c6/11340057/a3794357fee5/12866_2024_3465_Fig1_HTML.jpg

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