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利用实时聚合酶链反应确定的细菌清除率作为及时替代标志物,评估重症鲍曼不动杆菌菌血症患者抗生素使用的适宜性。

Using the rate of bacterial clearance determined by real-time polymerase chain reaction as a timely surrogate marker to evaluate the appropriateness of antibiotic usage in critical patients with Acinetobacter baumannii bacteremia.

机构信息

Department of Internal Medicine, Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Crit Care Med. 2012 Aug;40(8):2273-80. doi: 10.1097/CCM.0b013e3182515190.

Abstract

OBJECTIVE

Bacteremia caused by Acinetobacter baumannii is becoming more frequent among critically ill patients, and has been associated with high mortality and prolonged hospital stay. Multidrug resistance and delay in blood culture have been shown to be significant barriers to appropriate antibiotic treatment. Quantitative polymerase chain reaction assays were recently used to monitor bacterial loads; we hypothesized that the rate of bacterial clearance determined by quantitative polymerase chain reaction can be used as a timely surrogate marker to evaluate the appropriateness of antibiotic usage.

DESIGN

Prospective observational study.

SETTING

University hospital and research laboratory.

PATIENTS

Patients with culture-proven A. baumannii bacteremia in the intensive care units were prospectively enrolled from April 2008 to February 2009.

INTERVENTIONS

Plasmid Oxa-51/pCRII-TOPO, which contained a 431-bp fragment of the A. baumannii-specific Oxa-51 gene in a pCRII-TOPO vector, was used as the standard. Sequential bacterial DNA loads in the blood were measured by a quantitative polymerase chain reaction assay.

MEASUREMENTS AND MAIN RESULTS

We enrolled 51 patients with A. baumannii bacteremia, and examined 318 sequential whole blood samples. The initial mean bacterial load was 2.15 log copies/mL, and the rate of bacterial clearance was 0.088 log copies/mL/day. Multivariate linear regression using the generalized estimation equation approach revealed that the use of immunosuppressants was an independent predictor for slower bacterial clearance (coefficient, 1.116; p<.001), and appropriate antibiotic usage was an independent predictor for more rapid bacterial clearance (coefficient, -0.995; p<.001). Patients with a slower rate of bacterial clearance experienced higher in-hospital mortality (odds ratio, 2.323; p=.04)

CONCLUSIONS

Immunosuppression and appropriate antibiotic usage were independent factors affecting the rate of clearance of A. baumannii bacteremia in critical patients. These findings highlight the importance of appropriate antibiotic usage and development of effective antibiotics against A. baumannii in an era of emerging antibiotic resistance. The rate of bacterial clearance could serve as a timely surrogate marker for evaluating the appropriateness of antibiotics.

摘要

目的

鲍曼不动杆菌引起的菌血症在重症患者中越来越常见,与高死亡率和住院时间延长有关。多药耐药和血培养延迟已被证明是抗生素治疗不当的重要障碍。定量聚合酶链反应检测已被用于监测细菌负荷;我们假设,通过定量聚合酶链反应确定的细菌清除率可以作为及时的替代标志物,用于评估抗生素使用的适当性。

设计

前瞻性观察性研究。

设置

大学医院和研究实验室。

患者

2008 年 4 月至 2009 年 2 月,重症监护病房培养阳性的鲍曼不动杆菌菌血症患者前瞻性纳入研究。

干预

质粒 Oxa-51/pCRII-TOPO,其中包含 A.baumannii 特异性 Oxa-51 基因的 431bp 片段,位于 pCRII-TOPO 载体中,用作标准。通过定量聚合酶链反应检测血液中连续的细菌 DNA 负荷。

测量和主要结果

我们纳入了 51 例鲍曼不动杆菌菌血症患者,检测了 318 份连续全血样本。初始平均细菌负荷为 2.15log 拷贝/mL,细菌清除率为 0.088log 拷贝/mL/天。使用广义估计方程方法的多变量线性回归显示,使用免疫抑制剂是细菌清除较慢的独立预测因素(系数,1.116;p<.001),适当的抗生素使用是细菌清除较快的独立预测因素(系数,-0.995;p<.001)。细菌清除率较慢的患者院内死亡率较高(比值比,2.323;p=.04)。

结论

免疫抑制和适当的抗生素使用是影响重症患者鲍曼不动杆菌菌血症清除率的独立因素。这些发现强调了在抗生素耐药性不断出现的时代,适当的抗生素使用和开发针对鲍曼不动杆菌的有效抗生素的重要性。细菌清除率可以作为评估抗生素使用适当性的及时替代标志物。

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