High and increasing Oxa-51 DNA load predict mortality in Acinetobacter baumannii bacteremia: implication for pathogenesis and evaluation of therapy.

High and increasing Oxa-51 DNA load predict mortality in Acinetobacter baumannii bacteremia: implication for pathogenesis and evaluation of therapy.
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DOI:
10.1371/journal.pone.0014133
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发表时间:
2010-11-30
期刊:
影响因子:
3.7
通讯作者:
Wang WK
Wang WK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chuang YC;Chang SC;Wang WK

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虽然病毒载量的定量已成功地应用于临床医学,并为几种病毒性疾病提供了有价值的见解和有用的标志物,但测量细菌DNA载量以预测结果或监测治疗反应的潜力在很大程度上仍未开发。我们通过调查鲍曼不动杆菌菌血症中的细菌载量来测试这种可能性,鲍曼不动杆菌菌血症是一种快速增加的医院感染,其特征在于高死亡率,耐药性,多种和复杂的风险因素,所有这些都迫切需要良好的标志物来评估治疗方法。我们建立了一种基于A.鲍曼不动杆菌特异性基因Oxa-51,并进行了前瞻性研究,以检查A.在来自51名成人患者(17名存活者,34名非存活者)的318份连续血液样本中检测鲍曼不动杆菌载量。重症监护室的鲍曼菌血症Oxa-51 DNA载量在第1、2和3天在非存活者中显著高于存活者(P分别为0.03、0.001和0.006)。 与存活者相比,死亡者具有更高的最大Oxa-51 DNA载量和从0天到3天的增加趋势(P<0.001),这与Pitt菌血症评分一起通过多变量分析是死亡率的独立预测因子(最大Oxa-51 DNA和Oxa-51 DNA变化分别为P=0.014和0.016)。 Kaplan-Meier分析显示,具有不同最大Oxa-51 DNA和从第0天至第3天Oxa-51 DNA变化的患者的生存曲线显著不同。高Oxa-51 DNA载量及其初始增加可预测死亡率。此外,监测血液中Oxa-51 DNA载量可为评估抗A.鲍曼不动杆菌在未来的临床研究中。
While quantification of viral loads has been successfully employed in clinical medicine and has provided valuable insights and useful markers for several viral diseases, the potential of measuring bacterial DNA load to predict outcome or monitor therapeutic responses remains largely unexplored. We tested this possibility by investigating bacterial loads in Acinetobacter baumannii bacteremia, a rapidly increasing nosocomial infection characterized by high mortality, drug resistance, multiple and complicated risk factors, all of which urged the need of good markers to evaluate therapeutics. We established a quantitative real-time PCR assay based on an A. baumannii-specific gene, Oxa-51, and conducted a prospective study to examine A. baumannii loads in 318 sequential blood samples from 51 adults patients (17 survivors, 34 nonsurvivors) with culture-proven A. baumannii bacteremia in the intensive care units. Oxa-51 DNA loads were significantly higher in the nonsurvivors than survivors on day 1, 2 and 3 (P = 0.03, 0.001 and 0.006, respectively). Compared with survivors, nonsurvivors had higher maximum Oxa-51 DNA load and a trend of increase from day 0 to day 3 (P<0.001), which together with Pitt bacteremia score were independent predictors for mortality by multivariate analysis (P = 0.014 and 0.016, for maximum Oxa-51 DNA and change of Oxa-51 DNA, respectively). Kaplan-Meier analysis revealed significantly different survival curves in patients with different maximum Oxa-51 DNA and change of Oxa-51 DNA from day 0 to day 3. High Oxa-51 DNA load and its initial increase could predict mortality. Moreover, monitoring Oxa-51 DNA load in blood may provide direct parameters for evaluating new regimens against A. baumannii in future clinical studies.