Measurement of Klebsiella Intestinal Colonization Density To Assess Infection Risk.
Measurement of Klebsiella Intestinal Colonization Density To Assess Infection Risk.
复制标题
DOI：
10.1128/msphere.00500-21
复制
发表时间：
2021-06-30
期刊：
影响因子：
4.8
通讯作者：
Bachman MA
中科院分区：
文献类型：
--
作者：
Sun Y;Patel A;SantaLucia J;Roberts E;Zhao L;Kaye K;Rao K;Bachman MA
肺炎克雷伯氏菌及其近缘种克雷伯氏菌。variicola和K.准肺炎是卫生保健相关感染的常见原因，并且患者经常被其肠道定殖菌株感染。为了评估克雷伯氏菌定植密度与后续感染之间的关联，进行了病例对照研究。建立了克雷伯氏菌多重定量PCR（qPCR）检测方法，并对该方法进行了验证。pneumoniae，克雷伯氏菌K. variicola和克螟K.与直肠拭子中总细菌DNA拷贝数相比，克雷伯氏菌属感染的病例基于临床定义鉴定，并且具有临床培养分离株和具有相同wzi荚膜序列类型的先前或同时定植分离株。对照组为无后续感染的定植患者，并根据年龄、性别和直肠拭子采集日期与病例进行2：1匹配。来自直肠拭子样本的qPCR用于测量克雷伯氏菌属的相对丰度与后续感染之间的关联。克雷伯菌qPCR相对丰度与16 S测序结果高度相关（ρ = 0.79; P < 0.001）。病例组克雷伯菌相对丰度中位数（15.7% [四分位距{IQR}，0.93 - 52.6%]）（n = 83）高于对照组（1.01% [IQR，0.02 - 12.8%]）（n = 155）（P < 0.0001）。使用治疗加权的逆概率调整多个临床协变量，克雷伯菌相对丰度>22%与总体感染相关（比值比[OR]，2.87 [95%置信区间{CI}，1.64 - 5.03]）（P = 0.0003）和次要分析中的菌血症（OR，4.137 [95%CI，1.448至11.818]）（P = 0.0084）。通过qPCR测量定植密度可能代表一种新的方法来识别有克雷伯菌感染风险的住院患者。重要性细菌病原体的定植通常先于感染，并提供了一个机会窗口，以防止这些感染摆在首位。克雷伯菌定植与随后的感染显著且可重复相关;然而，在个体患者中增强或减轻这种风险的因素尚不清楚。本研究开发了一种测定住院患者直肠拭子中克雷伯菌定植密度（相对于总粪便细菌）的方法。将该测定应用于238名定殖患者，高克雷伯氏菌密度（定义为>22%的总细菌）与随后的感染显著相关。基于广泛可用的PCR技术，这种类型的检测可以部署在临床实验室中，以识别克雷伯氏菌感染风险增加的患者。随着新型治疗方法的开发，以消除肠道微生物组中的病原体，快速克雷伯氏菌定植密度测定可以确定谁将受益于这种类型的感染预防干预的患者。
Klebsiella pneumoniae and the closely related species K. variicola and K. quasipneumoniae are common causes of health care-associated infections, and patients frequently become infected with their intestinal colonizing strain. To assess the association between Klebsiella colonization density and subsequent infections, a case-control study was performed. A multiplex quantitative PCR (qPCR) assay was developed and validated to quantify Klebsiella (K. pneumoniae, K. variicola, and K. quasipneumoniae combined) relative to total bacterial DNA copies in rectal swabs. Cases of Klebsiella infection were identified based on clinical definitions and having a clinical culture isolate and a preceding or coincident colonization isolate with the same wzi capsular sequence type. Controls were colonized patients without subsequent infection and were matched 2:1 to cases based on age, sex, and rectal swab collection date. qPCR from rectal swab samples was used to measure the association between the relative abundance of Klebsiella and subsequent infections. The Klebsiella relative abundance by qPCR was highly correlated with 16S sequencing (ρ = 0.79; P < 0.001). The median Klebsiella relative abundance was higher in cases (15.7% [interquartile range {IQR}, 0.93 to 52.6%]) (n = 83) than in controls (1.01% [IQR, 0.02 to 12.8%]) (n = 155) (P < 0.0001). Adjusting for multiple clinical covariates using inverse probability of treatment weighting, a Klebsiella relative abundance of >22% was associated with infection overall (odds ratio [OR], 2.87 [95% confidence interval {CI}, 1.64 to 5.03]) (P = 0.0003) and with bacteremia in a secondary analysis (OR, 4.137 [95% CI, 1.448 to 11.818]) (P = 0.0084). Measurement of colonization density by qPCR could represent a novel approach to identify hospitalized patients at risk for Klebsiella infection. IMPORTANCE Colonization by bacterial pathogens often precedes infection and offers a window of opportunity to prevent these infections in the first place. Klebsiella colonization is significantly and reproducibly associated with subsequent infection; however, factors that enhance or mitigate this risk in individual patients are unclear. This study developed an assay to measure the density of Klebsiella colonization, relative to total fecal bacteria, in rectal swabs from hospitalized patients. Applying this assay to 238 colonized patients, a high Klebsiella density, defined as >22% of total bacteria, was significantly associated with subsequent infection. Based on widely available PCR technology, this type of assay could be deployed in clinical laboratories to identify patients at an increased risk of Klebsiella infections. As novel therapeutics are developed to eliminate pathogens from the gut microbiome, a rapid Klebsiella colonization density assay could identify patients who would benefit from this type of infection prevention intervention.