获得性MRSA肺炎患者死亡率与血清万古霉素水平及MRSA最低抑菌浓度相关性分析

The relationship between MRSA pneumonia mortality and serum levels of vancomycin, vancomycin minimum inhibitory concentration

目的探讨AgrⅡ基因、血清万古霉素水平、万古霉素最低抑菌浓度（MIC）与ICU获得性耐甲氧西林金黄色葡萄球菌（MRSA）肺炎患者30d内死亡率的相关性。方法研究对象为2013—06—2015—12我院ICU收治的213例获得性MRSA肺炎患者。采用E试验法和微量肉汤稀释法测定患者万古霉素MIC。分析的变量包括年龄、性别、疾病、血清万古霉素谷浓度、急性生理与慢性健康状况评分Ⅱ（APACHEⅡ）和AgrⅡ基因。评价指标是患者30d死亡率。结果90例（42．3％）患者在MRSA培养后30d内死亡。多元回归结果表明，只有APACHEⅡ评分与患者30d死亡率相关（P=0．02）。E试验方法检测结果表明，18例（8．5％）MIC≥1．5μg,／mL肺炎患者死亡，27例（12．7％）患者存活（P=0．74）。微量肉汤稀释法检测结果表明，28例（13．1％）MIC为1．0μg／mL患者死亡，47例（22．1％）存活（P=0．90）。生存患者APACHEII评分中位数为22．7，死亡患者APACHEⅡ评分中位数为25．2（P=0．02）。AgrⅡ基因与患者30d死亡率无关。结论MIC≤1．5wg／mL（E试验方法）或MIC≤1．0μg／mL（微量肉汤稀释法）的医院获得性MRSA肺炎患者30d死亡率较高。APACHEⅡ评分与30d死亡率独立相关，与MIC无关。AgrⅡ基因与30d死亡率无关。

Objective To investigate the relationship between molecular markers such as the Agr Ⅱ genes, serum vancomycin levels and vancomycin minimum inhibitory concentration （MIC）, and the 30 - day mortality rate of patients with nosocomial methicillin - resistant Staphylococcus aureus （MRSA） pneumonia in an intensive care unit （ICU）. Methods 213 patients with MRSA hospital - acquired pneumonia in ICU of our hospital from 2013 June to 2015 December. The MIC for vancomycin was determined by using the E - test and broth microdilution methods. Variables analyzed included age, sex, comorbid conditions, serum vancomycin trough concentration, the acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ） score and the presence of the Agr Ⅱ gene. The primary outcome was mortality at 30 days. Results 90 patients （42.3%） died within 30 days after MRSA culture. Multiple regression analysis showed that only APACHE Ⅱ score associated with 30 - day mortality （P = 0.02）. E- test results showed that 18 patients with isolates exhibiting an MIC ≥ 1.5 p,g/mL died, 27 patients （ 12.7% ） survived （ P = 0. 74 ）. The broth microdilution results showed that 28 patients （13.1%） with isolates exhibiting an MIC 1.0 μg/mL died, 47 patients （22. 1% ） survived （P = 0.90）. The median APACHE Ⅱ score of survival patients were 22.7, and the median APACHE Ⅱ score of death patients were 25.2 （P = 0.02）. The presence of the Agr Ⅱ gene was not related to the 30 - day mortality rate. Conclusion The hospital - acquired MRSA patients who MIC ≤ 1.5 μg / mL （E test method） or MIC≤I. 0 μg/mL （the broth microdilution method） had higher 30- day mortality. The APACHE Ⅱ scores which provides an overall estimate of ICU mortality were independently associated with mortality, regardless of the MICs determined. Molecular markers, such as the Agr Ⅱ gene, were not associated with higher mortality in the present study.