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Risk Factors and Clinical Outcomes of Pan-drug Resistant Acinetobacter baumannii Bacteremia
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摘要:
目的 比较泛耐药鲍曼不动杆菌(pan-drug resistant Acinetobacter baumannii, PDRAB)菌血症与非泛耐药鲍曼不动杆菌(non-pan-drug resistant Acinetobacter baumannii, NPDRAB)菌血症的临床资料, 探讨PDRAB菌血症的危险因素及其临床结局。 方法 本研究为回顾性队列研究, 纳入对象为2010年1月1日至2012年12月31日就诊于北京协和医院的鲍曼不动杆菌菌血症患者, 采用统一的标准表格收集患者的临床资料和检验结果, 以鲍曼不动杆菌血培养标本采集14 d内发生院内死亡为主要临床结局。 结果 共纳入52例鲍曼不动杆菌菌血症患者, 平均年龄(54±20)岁, 其中男性30例(57.7%); 平均急性生理与慢性健康状况Ⅱ(acute physiology and chronic health evaluation Ⅱ, APACHE Ⅱ)评分(21±9)分, 平均序贯器官衰竭评估(sepsis-related organ failure assessment, SOFA)评分(10±5)分; 鲍曼不动杆菌菌血症发生前, 患者中位住院时间为12 d(7~20 d); 仅6例患者对碳青霉烯类药物敏感。33例患者感染NPDRAB, 19例感染PDRAB。在感染鲍曼不动杆菌前, PDRAB患者与NPDRAB患者比较, 接受机械通气概率更大(94.7%比63.6%, P=0.031), 住院时间更长(中位住院时间17 d比10 d, P=0.025)。鲍曼不动杆菌菌血症患者14 d死亡率为67.3%(35/52)。多因素分析提示, 脓毒性急性肾损伤(OR 7.9, 95% CI 1.113~55.448, P=0.039)、不适当抗菌药物治疗(OR 9.4, 95% CI 1.020~87.334, P=0.048)和降钙素原水平(OR 1.3, 95% CI 1.332~1.088, P=0.005)是鲍曼不动杆菌菌血症患者14 d死亡的独立危险因素。 结论 鲍曼不动杆菌具有多重耐药性, 甚至对目前所有全身用抗菌药物均不敏感, 感染患者死亡率较高。菌血症发生前接受机械通气和住院时间是PDRAB菌血症的危险因素, 但PDRAB感染本身不能作为判断患者预后不良的指标。不适当抗菌药物治疗、脓毒性急性肾损伤和降钙素原水平是鲍曼不动杆菌菌血症患者14 d死亡的独立危险因素。 Abstract:Objective To determine the risk factors and outcomes of pan-drug resistant Acinetobacter baumannii(PDRAB) bacteremia by comparing clinical data of PDRAB patients with those of non-pan-drug resistant Acinetobacter baumannii (NPDRAB) bacteremia. Methods This retrospective cohort study included patients with Acinetobacter baumannii bacteremia diagnosed and treated in Peking Union Medical College Hospital during January 1, 2010 and December 31, 2012. Clinical data and laboratory test results of the patients were collected with unified forms. The primary clinical outcome was in-hospital death within 14 days after sample collection for blood culture of Acinetobacter baumannii. Results A total of 52 patients with Acinetobacter baumannii bacteremia were included, with the mean age of 54±20 years and including 30 (57.7%) males. The mean acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sepsis-related organ failure assessment (SOFA) score were 21±9 and 10±5, respectively. The median length of hospital stay before Acinetobacter baumannii bacteremia was 12 days (7-20 days). Among these patients, only 6 cases were sensitive to carbapenem. Thirty-three cases were infected by NPDRAB and 19 by PDRAB. Compared with NPDRAB patients, PDRAB patients had a higher rate of receiving mechanical ventilation (94.7% vs. 63.6%, P=0.031) and a longer hospital stay (median:17 days vs. 10 days, P=0.025) before Acinetobacter baumannii infection. The 14-day mortality rate in patients with Acinetobacter baumannii bacteremia was 67.3% (35/52). In multivariate analysis, septic acute kidney injury[odds ratio (OR) 7.9, 95% confidence interval (CI) 1.113-55.448, P=0.039], inappropriate anti-microbial therapy (OR 9.4, 95% CI 1.020-87.334, P=0.048), and procalcitonin level (OR 1.3, 95% CI 1.332-1.088, P=0.005) were independent risk factors of 14-day mortality in Acinetobacter baumannii bacteremia patients. Conclusions Acinetobacter baumannii has multi-drug resistance and is even not susceptible to all currently available systemic antimicrobials. Acinetobacter baumannii infection is associated with high mortality rate. Mechanical ventilation and long hospital stay before occurrence of bacteremia are risk factors for PDRAB bacteremia. However, PDRAB infection itself is not a predictor of poor prognosis. Inappropriate antimicrobial therapy, septic acute kidney injury, and procalcitonin level are independent risk factors of 14-day mortality in Acinetobacter baumannii bacteremia. -
表 1 PDRAB与NPDRAB感染患者人口统计学和临床特征比较
特征 NPDRAB PDRAB P值 例数[n(%)] 33(63.5) 19(36.5) 年龄(x±s, 岁) 56±21 47±20 0.102 男性[n(%)] 22(66.7) 8(42.1) 0.084 报告时间(x±s, d) 10±6 13±11 0.345 APACHE Ⅱ评分(x±s，分) 21±10 20±9 0.419 SOFA评分(x±s，分) 10±6 10±5 0.877 全身基础疾病[n(%)] 高血压 7(21.2) 4(21.1) 1.000 糖尿病 9(27.3) 4(21.1) 0.868 慢性阻塞性肺疾病 3(9.1) 2(10.5) 1.000 实体肿瘤 10(30.3) 7(36.8) 0.628 脑血管意外 7(21.2) 3(15.8) 0.910 自身免疫性疾病 12(36.4) 11(57.8) 0.132 贫血 27(81.8) 17(89.5) 0.736 甾体类药物使用[n(%)] 17(51.5) 13(68.4) 0.235 既往抗生素使用[n(%)] 24(72.7) 14(73.7) 0.940 ≥2类抗生素[n(%)] 16(50.0) 10(52.6) 0.856 三代头孢菌素[n(%)] 10(31.3) 5(26.3) 0.708 碳青霉烯类[n(%)] 21(65.6) 13(68.4) 0.838 三代头孢菌素+碳青霉烯类
[n(%)]3(9.4) 3(15.8) 0.812 β-内酰胺酶抑制剂[n(%)] 13(40.6) 4(21.4) 0.152 米诺环素/四环素[n(%)] 1(3.1) 2(10.0) 0.672 ICU收住时间＞7 d [n(%)] 26(78.8) 12(63.2) 0.221 肺炎[n(%)] 26(78.8) 16(84.2) 0.910 菌血症发生前住院时间
[M(Q1~Q3)，d]10(6~17) 17(9~63) 0.025 真菌感染[n(%)] 9(27.3) 10(52.6) 0.067 机械通气[n(%)] 21(63.6) 18(94.7) 0.031 病毒感染[n(%)] 2(6.1) 3(15.8) 0.511 PDRAB：泛耐药鲍曼不动杆菌；NPDRAB：非泛耐药鲍曼不动杆菌；APACHE Ⅱ：急性生理与慢性健康状况Ⅱ；SOFA：序贯器官衰竭评估；ICU:重症监护病房 
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表 2 PDRAB和NPDRAB感染患者临床结局比较
组别 例数
[n(%)]阳性报警时间
[M(Q1~Q3)，h]脓毒性AKI
[n(%)]脓毒性休克
[n(%)]导管相关感染
[n(%)]PCT水平
[M(Q1~Q3)，ng/ml]不适当抗菌药物
治疗[n(%)]14 d死亡
[n(%)]NPDRAB 33(63.5) 9(6~12) 15(45.4) 17(48.6) 23(69.7) 4.23(1.79~10.25) 21(63.6) 20(60.6) PDRAB 19(36.5) 10(8~10) 12(63.1) 11(57.9) 16(84.2) 4.57(1.06~10.00) 19(100) 15(78.9) P值 0.345 0.219 0.513 0.406 0.947 0.008 0.175 PDRAB、NPDRAB：同表 1；AKI：急性肾损伤；PCT：降钙素原
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表 3 鲍曼不动杆菌菌血症14 d死亡的危险因素单因素分析
危险因素 存活组 非存活组 P值 例数[n(%)] 17(32.7) 35(67.3) 年龄(x±s, 岁) 57.7±20.6 50.3±18.8 0.249 男性[n(%)] 10(58.8) 20(57.1) 0.908 菌血症发生前住院时间
[M(Q1~Q3), d]11(7.5~21.5) 14(6.0~20.0) 0.747 APACHE Ⅱ评分
(x±s, 分)16.8±7.4 22.6±9.6 0.028 SOFA评分(x±s, 分) 6.8±4.4 11.2±5.0 0.004 甾体类药物使用
[n(%)]9(52.9) 21(60.0) 0.629 高血压[n(%)] 6(35.3) 5(14.3) 0.168 糖尿病[n(%)] 5(29.4) 8(22.9) 0.864 慢性阻塞性肺疾病
[n(%)]3(17.6) 2(5.7) 0.386 实体肿瘤[n(%)] 6(35.3) 11(31.4) 0.780 脑血管意外[n(%)] 5(29.4) 5(14.3) 0.356 自身免疫性疾病
[n(%)]5(29.4) 18(51.4) 0.134 贫血[n(%)] 14(82.4) 30(85.7) 1.000 既往抗生素使用史
[n(%)]12(70.6) 26(74.3) 1.000 ICU收住时间＞7 d
[n(%)]15(88.2) 23(65.7) 0.166 机械通气[n(%)] 15(88.2) 34(97.1) 0.246 脓毒性AKI [n(%)] 4(23.5) 23(65.7) 0.004 肺炎[n(%)] 13(76.5) 29(82.9) 0.863 导管相关感染[n(%)] 13(76.5) 26(74.3) 1.000 真菌感染[n(%)] 3(17.6) 16(45.7) 0.049 病毒感染[n(%)] 0(0.0) 5(14.3) 0.255 痰培养[n(%)] 阳性 13(76.5) 32(91.4) 0.294 存在PDR细菌 6(35.3) 12(34.3) 0.943 存在XDR细菌 13(76.5) 29(82.9) 0.863 血培养[n(%)] 存在PDR细菌 4(23.5) 15(42.9) 0.175 存在XDR细菌 15(88.2) 33(94.3) 0.831 PCT水平[M(Q1~Q3)，
ng/ml]2.6(0.77~3.82) 10(4.63~26.48) ＜0.001 脓毒性休克[n(%)] 6(35.6) 28(80.0) 0.001 不适当抗菌药物治疗
[n(%)]10(58.8) 30(85.7) 0.031 药物联用[n(%)] 9(52.9) 15(42.9) 0.494 碳青霉烯类[n(%)] 9(52.9) 12(34.3) 0.198 磺胺甲恶唑[n(%)] 16(94.1) 28(80.0) 0.361 抗球菌治疗[n(%)] 12(70.6) 23(65.7) 0.725 抗真菌治疗[n(%)] 14(82.4) 26(74.3) 0.767 抗病毒治疗[n(%)] 16(94.1) 33(94.3) 1.000 APACHE Ⅱ、SOFA、ICU：同表 1；AKI、PCT：同表 2；PDR：泛耐药; XDR：广泛耐药
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