Analysis of clinical characteristics and risk factors of death in critical burn patients complicated with invasive fungal infection
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摘要:
目的 探讨危重烧伤并发侵袭性真菌感染患者的临床特征及死亡的危险因素。 方法 采用回顾性病例系列研究方法。2017年1月—2022年12月，郑州市第一人民医院收治88例符合入选标准的危重烧伤并发侵袭性真菌感染患者，其中男61例、女27例，年龄26~74岁。统计患者侵袭性真菌感染部位和病原菌检出情况。依据入院后28 d内的生存结局，将患者分为存活组（63例）和死亡组（25例）。比较2组患者入院时年龄、性别、体重、烧伤总面积、合并吸入性损伤情况、合并高血压和糖尿病情况、急性生理学和慢性健康状况评价Ⅱ（APACHE Ⅱ）评分以及伤后入院时间等基本资料与伤情，入院后24 h内检测的白细胞计数、血小板计数、红细胞计数、单核细胞计数、中性粒细胞计数、淋巴细胞计数、丙氨酸转氨酶、天冬氨酸转氨酶、葡萄糖、肌酐、尿素氮、D-二聚体、半乳甘露聚糖（GM）、1，3-β-D葡聚糖和肌酸激酶等血生化指标水平，治疗过程中连续性肾脏替代治疗、呼吸机辅助呼吸、气管切开、深静脉置管、手术植皮>2次等有创操作和应用血管活性药物情况，入院后1、3、7、14 d的C反应蛋白（CRP）、降钙素原、乳酸、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）等感染指标水平，治疗过程中病原菌检出情况。对数据行独立样本 t检验、重复测量方差分析、 χ 2检验、Mann-Whitney U检验、Bonferroni校正。行多因素logistic回归分析，筛选影响危重烧伤并发侵袭性真菌感染患者死亡的独立危险因素。 结果 侵袭性真菌感染的主要部位为创面（67例）和血流（46例），感染的真菌主要为假丝酵母菌属真菌（58株），病原菌混合感染者共30例。与存活组比较，死亡组患者入院时APACHE Ⅱ评分、合并吸入性损伤和高血压比例均明显升高（ t=2.11， χ 2值分别为6.26、9.48， P<0.05），其余基本资料和伤情均无明显变化（ P>0.05）。与存活组比较，死亡组患者入院后24 h内D-二聚体、GM、1，3-β-D葡聚糖水平均明显升高（ t值分别为2.42、2.05、2.21， P<0.05），入院后24 h内其余血生化指标及治疗过程中行各项有创操作和应用血管活性药物比例均无明显变化（ P>0.05）。2组患者入院后1、3 d的感染指标水平均相近（ P>0.05），死亡组患者入院后7 d的降钙素原与入院后14 d的CRP、降钙素原、乳酸、IL-6和TNF-α水平以及病原菌混合感染比例均明显高于存活组（ t值分别为4.69、3.89、6.70、6.14、4.65、3.26， χ 2=12.67， P<0.05）。多因素logistic回归分析显示，合并吸入性损伤、合并高血压和病原菌混合感染均为影响危重烧伤并发侵袭性真菌感染患者死亡的独立危险因素（比值比分别为5.98、4.67、6.19，95%置信区间分别为1.42~15.39、1.41~25.28、1.86~20.58， P<0.05）。 结论 危重烧伤并发侵袭性真菌感染患者感染的主要部位为创面和血流，感染的真菌主要为假丝酵母菌属真菌，病原菌混合感染比例较高；该类患者死亡的独立危险因素为合并吸入性损伤、合并高血压和病原菌混合感染。 Abstract:Objective To investigate the clinical characteristics and risk factors of critical burn patients complicated with invasive fungal infection. Methods A retrospective case series study was conducted. From January 2017 to December 2022, 88 critical burn patients combined with invasive fungal infection who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 61 males and 27 females, aged 26-74 years. Data on invasive fungal infection sites and the detection of pathogens in patients were recorded. According to the survival outcome within 28 days after admission, the patients were divided into survival group (63 cases) and death group (25 cases). The following data of patients were compared between the two groups, including the basic data and injuries of patients at admission such as age, sex, body weight, total burn area, combination of inhalation injury, combination of hypertension and diabetes, acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) score, and admission time after burns, the levels of blood biochemical indexes within 24 h after admission such as white blood cell count, platelet count, red blood cell count, monocyte count, neutrophil count, lymphocyte count, alanine transaminase, aspartate transaminase, glucose, creatinine, urea nitrogen, D-dimer, galactomannan (GM), 1,3-β-D glucan, and creatine kinase, the application of invasive procedures and vasoactive drugs during the treatment such as continuous renal replacement therapy, ventilator-assisted breathing, tracheotomy, deep vein catheterization, skin grafting >2 times, the levels of infection indicators on post admission day (PAD) 1, 3, 7, and 14 including C-reactive protein (CRP), procalcitonin, lactic acid, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the detection of pathogens in the process of treatment. Data were statistically analyzed with independent sample t test, analysis of variance for repeated measurement, chi-square test, Mann-Whitney U test, and Bonferroni correction. Multivariate logistic regression analysis was performed to screen the independent risk factors that affected death of critical burn patients complicated with invasive fungal infection. Results The main sites of invasive fungal infection were the wounds (67 cases) and blood stream (46 cases), with Candida fungi (58 strains) as the main strain for fungi infection, and there were a total of 30 cases of infection with mixed pathogenic bacteria. Compared with those in survival group, the APACHE Ⅱ score, proportions of combination with inhalation injury and hypertension of patients in death group were significantly increased ( t=2.11, with χ 2 values of 6.26 and 9.48, respectively, P<0.05), while the other basic data and injury condition had no significant changes ( P>0.05). Compared with those in survival group, the levels of D-dimer, GM, and 1,3-β-D glucan of patients in death group were significantly increased within 24 h after admission (with t values of 2.42, 2.05, and 2.21, respectively, P<0.05), while the other blood biochemical indexes within 24 h after admission, as well as the proportions of applying invasive procedures and application of vasoactive drugs during the treatment process were not significantly changed ( P>0.05). The levels of infection indicators of patients on PAD 1 and 3 were similar between the two groups ( P>0.05). The procalcitonin level on PAD 7 and the levels of CRP, procalcitonin, lactic acid, IL-6, and TNF-α on PAD 14, as well as the proportion of infection with mixed pathogenic bacteria of patients in death group were significantly higher than those in survival group (with t values of 4.69, 3.89, 6.70, 6.14, 4.65, and 3.26, respectively, χ 2=12.67, P<0.05). Multivariate logistic regression analysis showed that combination with inhalation injury, combination with hypertension, and infection with mixed pathogenic bacteria were independent risk factors for death of critical burn patients complicated with invasive fungal infection (with odds ratios of 5.98, 4.67, and 6.19, respectively, 95% confidence intervals of 1.42-15.39, 1.41-25.28, and 1.86-20.58, respectively, P<0.05). Conclusions The main sites of infection in critical burn patients complicated with invasive fungal infection are the wounds and blood stream, with Candida fungi as the main strain for fungi infection, and a large proportion of infection with mixed pathogenic bacteria. The combined inhalation injury, combined hypertension, and infection with mixed pathogenic bacteria are the independent risk factors for the death of those patients. -
Key words:
- Burns /
- Invasive fungal infections /
- Risk factors /
- Mixed infection
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参考文献
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表1 2组危重烧伤并发侵袭性真菌感染患者基本资料与伤情比较
组别 例数 性别 年龄（岁， 体重（kg， 烧伤总面积（%TBSA， 合并基础疾病（例） 合并吸入性损伤（例） APACHE Ⅱ评分（分， 伤后入院时间［h， M（ Q 1 ，Q 3）］ 男 女 高血压 糖尿病 存活组 63 43 20 49±11 67±9 55±13 18 18 35 15±4 45（25，96） 死亡组 25 18 7 53±10 63±6 59±12 16 6 21 17±6 52（29，100） 统计量值 χ 2=0.12 t=1.75 t=1.91 t=1.31 χ 2=9.48 χ 2=0.19 χ 2=6.26 t=2.11 Z=1.37 P值 0.731 0.084 0.060 0.193 0.002 0.664 0.012 0.038 0.171 注：除伤后入院时间外，其余指标均为入院时情况；TBSA为体表总面积，APACHE Ⅱ为急性生理学和慢性健康状况评价Ⅱ 
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表2 2组危重烧伤并发侵袭性真菌感染患者入院后24 h内血生化指标比较（
组别 例数 WBC（×10 9/L） PLT（×10 9/L） RBC（×10 12/L） 单核细胞计数（×10 9/L） 中性粒细胞计数（×10 9/L） 淋巴细胞计数（×10 9/L） ALT（U/L） AST（U/L） 存活组 63 18±7 198±68 4.6±0.7 0.8±0.3 27±7 1.8±0.7 36±10 59±17 死亡组 25 21±7 224±106 4.3±0.8 0.8±0.3 25±5 2.1±1.1 40±12 61±17 t值 1.80 1.34 1.91 0.40 1.20 1.80 1.72 0.47 P值 0.075 0.184 0.060 0.693 0.235 0.075 0.094 0.638 注：WBC为白细胞计数，PLT为血小板计数，RBC为红细胞计数，ALT为丙氨酸转氨酶，AST为天冬氨酸转氨酶
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表3 2组危重烧伤并发侵袭性真菌感染患者入院后各时间点感染指标比较（
组别与时间点 例数 CRP（mg/L） 降钙素原（ng/mL） 乳酸（mmol/L） IL-6（pg/mL） TNF-α（pg/mL） 存活组 63 1 d 83±24 18±5 3.2±0.8 40±12 2.8±0.6 3 d 117±26 19±6 3.7±1.0 62±19 3.9±1.0 7 d 128±32 16±6 4.1±1.4 71±27 4.8±1.3 14 d 119±28 13±3 3.0±0.8 62±23 4.2±2.4 死亡组 25 1 d 87±25 19±6 3.5±0.9 42±13 2.9±1.2 3 d 130±36 22±7 4.1±1.7 67±23 4.3±1.3 7 d 144±43 23±9 4.6±1.5 82±33 5.4±2.0 14 d 151±49 21±8 5.1±2.6 93±38 6.1±2.5 t 1值 0.82 0.24 1.58 0.47 0.32 P 1值 0.414 0.461 0.119 0.641 0.752 t 2值 1.78 1.20 1.17 1.09 1.21 P 2值 0.079 0.076 0.251 0.278 0.230 t 3值 1.90 4.69 1.38 1.59 1.92 P 3值 0.061 0.001 0.171 0.116 0.058 t 4值 3.89 6.70 6.14 4.65 3.26 P 4值 0.001 0.001 0.001 0.001 0.002 注：CRP为C反应蛋白，IL-6为白细胞介素6，TNF-α为肿瘤坏死因子α；CRP、降钙素原、乳酸、IL-6和TNF-α的分组因素主效应， F值分别为11.96、40.17、22.96、10.78、10.14， P值均<0.001；时间因素主效应， F值分别为52.42、5.65、9.27、50.67、40.22， P值均<0.001；二者交互作用， F值分别为2.96、6.63、10.22、7.69、5.42， P值分别为0.042、<0.001、<0.001、<0.001、0.001； t 1值、 P 1值， t 2值、 P 2值， t 3值、 P 3值， t 4值、 P 4值分别为组间入院后1、3、7、14 d各指标比较所得
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表4 2组危重烧伤并发侵袭性真菌感染患者治疗过程中病原菌检出情况比较（株）
组别 例数 假丝酵母菌属真菌 曲霉菌属真菌 毛霉菌属真菌 细菌 合计 热带假丝酵母菌 白假丝酵母菌 都柏林假丝酵母菌 近平滑假丝酵母菌 黄曲霉菌 烟曲霉菌 其他曲霉菌 卷枝毛霉菌 雅致放射毛霉菌 根霉菌 鲍曼不动杆菌 肺炎克雷伯菌 大肠埃希菌 屎肠球菌 嗜麦芽窄食单胞菌 其他细菌 存活组 63 13 19 4 6 7 7 3 3 1 0 7 4 2 1 2 1 80 死亡组 25 5 8 1 2 10 6 2 1 1 4 4 3 2 0 1 2 52 注：其他曲霉菌指土曲霉菌、黑曲霉菌、米曲霉菌；其他细菌指奇异变形杆菌、铜绿假单细胞、溶血链球菌
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表5 影响88例危重烧伤并发侵袭性真菌感染患者死亡的多因素logistic回归分析结果
因素 比值比 95%置信区间 P值 病原菌混合感染 6.19 1.86~20.58 0.003 合并吸入性损伤 5.98 1.42~15.39 0.015 合并高血压 4.67 1.41~25.28 0.011 D-二聚体（μg/L） 1.07 0.96~1.19 0.213 1，3-β-D葡聚糖（pg/mL） 1.01 0.99~1.03 0.179
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