Department of Internal Medicine, National Taiwan University Hospital, and Institute of Microbiology, College of Medicine, National Taiwan University, Tapei, Taiwan.
PLoS One. 2010 Nov 30;5(11):e14133. doi: 10.1371/journal.pone.0014133.
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.
虽然病毒载量的定量分析已成功应用于临床医学，并为多种病毒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得到探索。我们通过研究鲍曼不动杆菌菌血症中的细菌负荷来检验这种可能性，鲍曼不动杆菌菌血症是一种迅速增加的医院获得性感染，其死亡率高、耐药性强、多种复杂的危险因素并存，所有这些都迫切需要良好的标志物来评估治疗效果。
我们建立了一种基于鲍曼不动杆菌特异性基因 Oxa-51 的定量实时 PCR 检测方法，并进行了一项前瞻性研究，以检测 51 例重症监护病房中经培养证实的鲍曼不动杆菌菌血症患者的 318 份连续血样中的鲍曼不动杆菌负荷。第 1、2 和 3 天，非幸存者的 Oxa-51 DNA 载量明显高于幸存者（P=0.03、0.001 和 0.006）。与幸存者相比，非幸存者的最大 Oxa-51 DNA 载量更高，从第 0 天到第 3 天呈上升趋势（P<0.001），多元分析显示最大 Oxa-51 DNA 载量和 Oxa-51 DNA 变化与 Pitt 菌血症评分一起是死亡率的独立预测因子（P=0.014 和 0.016）。Kaplan-Meier 分析显示，不同最大 Oxa-51 DNA 和第 0 天到第 3 天 Oxa-51 DNA 变化的患者之间的生存曲线有显著差异。
高 Oxa-51 DNA 载量及其初始增加可预测死亡率。此外，监测血液中的 Oxa-51 DNA 载量可能为未来临床研究中评估针对鲍曼不动杆菌的新方案提供直接参数。
