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由于原发疾病、代谢改变或术后免疫力低下等原因,肝胆外科肿瘤患者常因病原菌侵袭发生感染。利奈唑胺是市售的第一种人工合成的新型恶唑烷酮类抗菌药,被用于治疗革兰阳性球菌引起的感染,对多种革兰阳性菌均有活性,且与其他抗菌药无交叉耐药现象[1],常用于肝胆外科肿瘤患者的抗感染治疗。血液毒性是利奈唑胺最常见的临床不良反应,包括血小板减少、贫血与白细胞减少等,其中又以血小板减少的发生率最高[2]。回顾性研究提示,利奈唑胺引起的血小板减少与患者不良预后相关,可能会导致患者器官衰竭,病死率增高[3]。笔者选取本院2017年1月至2021年12月间应用利奈唑胺的肿瘤患者为样本,旨在分析给予患者使用利奈唑胺进行抗感染治疗时血小板减少的发生情况,并探索其影响因素,为临床治疗安全性提供依据。
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本研究共纳入有效病例104例,其中男性68例,女性36例;年龄26~82岁,平均年龄(60.93±11.53)岁;平均身高体重指数(BMI)(22.25±3.10);住院时长11~105 d,中位住院时间43 d;利奈唑胺单次给药剂量为0.6 g,给药频率为每12 h一次,静脉滴注102例,口服给药2例,用药时长4~26 d,中位用药时间10 d。腹腔感染患者(胆道感染、肝脓肿等)71例,其他感染患者(血液、肺部感染等)20例,合并两种以上感染患者(腹腔、血液、泌尿系统等)13例。当次入院接收外科手术的患者84例,未接受外科手术(如治疗感染、其他外科随访治疗等)的患者20例。
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应用利奈唑胺后,发生血小板减少的患者25人,未发生的患者79人,血小板减少发生率为24.0%。比较两组患者一般资料,BMI、基础疾病、是否进行外科手术、术前是否感染、住院天数,有无联用其他抗菌药物、血红蛋白、白蛋白等指标差异无统计学意义(P>0.05),性别、年龄、利奈唑胺使用时长、基础血小板计数、白细胞计数、ALT、AST、总胆红素、肌酐、估算肾小球滤过率等指标差异有统计学意义(P<0.05),结果见表1。
表 1 两组患者一般资料比较
临床指标 血小板减少组
(n=25)未发生组
(n=79)统计量 P值 性别[n(%)] 5.039 0.030 男 21(84.0) 47(59.5) 女 4(16.0) 32(40.5) 年龄(岁, $\bar x $±s) 65.7±7.7 59.4±12.1 −2.439 0.016 BMI(kg·m−2, $\bar x $±s) 22.1±3.1 22.3±3.1 0.333 0.739 基础疾病[n(%)] 10(40.0) 31(39.2) 0.005 1.000 高血压 9(36.0) 26(32.9) 0.081 0.811 糖尿病 5(20.0) 14(17.7) 0.066 0.773 冠心病 3(12.0) 4(5.1) − 0.355 是否进行外科手术[n(%)] 0.562 0.334 是 19(76.0) 65(82.3) 否 6(24.0) 14(17.7) 术前是否有感染1[n(%)] 0.313 0.220 是 5(26.3) 10(15.4) 否 14(73.7) 55(84.6) 利奈唑胺使用时长[n, M(Q1, Q3)] 12(9, 18) 10(7, 13) −2.144 0.032 住院天数[n, M(Q1, Q3)] 45(27, 64) 42(31, 56) −0.377 0.706 联用抗菌药[n(%)] 21(84.0) 72(91.1) 1.023 0.454 血小板计数[×109/L, M(Q1,Q3)] 135(121, 208) 228(172, 304) −3.671 <0.001 血红蛋白[g/L, M(Q1,Q3)] 94(86.5, 106) 99(91, 107) −1.172 0.241 白细胞计数[×109/L, M(Q1,Q3)] 13.91(9.2, 18.5) 9.37(7.2, 12.1) −2.906 0.004 白蛋白(g/L, $\bar x $±s) 35.2±4.7 35.8±4.6 0.572 0.569 ALT [U/L, M(Q1, Q3)] 85(32, 206) 36(20, 68) −3.413 0.001 AST [U/L, M(Q1, Q3)] 69(36.5, 69) 33(21, 41) −4.029 <0.001 总胆红素[μmol/L, M(Q1, Q3)] 49.1(23.9, 112.3) 27.3(17.5, 57.7) −2.267 0.023 肌酐[μmol/L, M(Q1, Q3)] 69(56, 132) 57(45, 75) −2.834 0.005 肾小球滤过率[ml/min, $\bar x $±s] 93.1±39.3 118.8±46.4 2.500 0.014 注1:比较两组接受外科手术的患者术前感染情况,血小板减少组(n=19),未发生组(n=65)。 -
以是否发生利奈唑胺相关性血小板减少为因变量(是=1;否=0);依据纳入研究的104例样本均值或中位数,结合临床意义及DAI[2]等的研究,以性别(男=1;女=0)、年龄(≥60 岁=1;<60岁=0)、利奈唑胺使用时长(≥12 d=1;<12 d=0)、基础血小板计数(≤200×109/L=1;>200×109/L =0)、白细胞计数(≥11×109/L=1;<11×109/L=0)、ALT(≥50 U/L=1;<50 U/L =0)、AST(≥50 U/L=1;<50 U/L=0)、总胆红素(≥46 μmol/L=1;<46 μmol/L=1)、肌酐(≥90 μmol/L=1;<90 μmol/L=0)、估算肾小球滤过率(≤100 ml∙min−1∙L−1=1;<100 ml∙min−1∙L−1=0)为自变量进行多因素logistic回归分析。结果表明年龄≥60岁、利奈唑胺使用时长≥12 d、基础血小板计数≤200×109/L、基础AST≥50 U/L、基础白细胞计数≥11×109/L是利奈唑胺相关性血小板减少发生的危险因素(P<0.05),结果见表2。
表 2 利奈唑胺相关性血小板减少的危险因素
变量 回归系数 标准误 统计量 OR P值 95%CI 年龄≥60岁 1.959 0.819 5.716 7.093 0.017 1.423~35.341 利奈唑胺使用时长≥12 d 1.481 0.703 4.437 4.399 0.035 1.108~17.455 血小板计数≤200×109/L 2.137 0.738 8.380 8.470 0.004 1.994~35.986 基础AST≥50 U/L 2.739 0.756 13.114 15.465 <0.001 3.513~68.085 基础白细胞计数≥11×109/L 2.437 0.755 10.420 11.436 0.001 2.605~50.217
Risk factors of linezolid-related thrombocytopenia in patients in the department of hepatobiliary surgery
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摘要:
目的 探讨肝胆外科肿瘤患者发生利奈唑胺相关性血小板减少的危险因素,为患者临床安全用药提供依据。 方法 选取本院2017年1月至2021年12月间应用利奈唑胺进行抗感染治疗的肿瘤患者,根据给予利奈唑胺后是否出现血小板减少,将患者分为血小板减少组和未发生组。比较两组患者一般资料与实验室指标,采用多因素logistic回归分析筛选发生利奈唑胺相关性血小板减少的危险因素。 结果 研究共纳入104例患者,其中接受外科手术患者84例,未接受外科手术患者20例。利奈唑胺相关性血小板减少发生率为24.0%。两组患者性别、年龄、利奈唑胺使用时长、血小板计数、白细胞计数、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素、肌酐、估算肾小球滤过率有显著性差异(P<0.05);logistic回归分析结果提示,年龄≥60岁(OR=7.093;P=0.017)、利奈唑胺使用时长≥12 d(OR=4.399;P=0.035)、基础血小板计数≤200×109/L(OR=8.470;P=0.004)、基础AST≥50 U/L(OR=15.465;P<0.001)、基础白细胞计数≥11×109/L(OR=11.436;P=0.001)是肿瘤患者发生利奈唑胺相关性血小板减少的危险因素。 结论 给肝胆外科肿瘤患者应用利奈唑胺时,医师需关注患者是否发生血小板减少的不良反应,尤其是年老、长疗程、基础血小板低、基础肝功能差及基础白细胞计数高的患者。 Abstract:Objective To provide the evidence for clinical medication safety by the investigation of the risk factors of linezolid-related thrombocytopenia in cancer patients in the department of hepatobiliary surgery. Methods Patients who received linezolid for anti-infective treatment from January 2017 to December 2021 were selected. The patients were divided into thrombocytopenia group and non-thrombocytopenia group according to whether thrombocytopenia occurred or not after administration of linezolid. The general data and laboratory indicators of the two groups were compared, and the risk factors of linezolid-related thrombocytopenia were screened by multivariate logistic regression analysis. Results A total of 104 patients were included in the study, including 84 patients who underwent surgery and 20 patients who did not. The incidence of linezolid-related thrombocytopenia was 24.0%. There were significant differences in gender, age, duration of linezolid use, platelet count, white blood cell count, alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin, creatinine, estimated glomerular filtration rate between the two groups (P<0.05); logistic regression analysis suggested that age ≥60 years (OR=7.093; P=0.017), duration of linezolid use ≥12 days (OR=4.399; P=0.035), baseline platelet count ≤200×109/L (OR=8.470; P=0.004), baseline AST≥50 U/L (OR=15.465; P<0.001), and baseline white blood cell count ≥11×109/L (OR=11.436; P=0.001) were the risk factors for linezolid-related thrombocytopenia in cancer patients. Conclusion During the treatment of linezolid in cancer patients, attention should be paid to the adverse reactions of thrombocytopenia in the patients, especially those with old age, long-term treatment, low baseline platelets, poor baseline liver function, and high baseline white blood cell counts. -
Key words:
- hepatobiliary surgery /
- cancer patients /
- linezolid /
- thrombocytopenia /
- risk factors
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表 1 两组患者一般资料比较
临床指标 血小板减少组
(n=25)未发生组
(n=79)统计量 P值 性别[n(%)] 5.039 0.030 男 21(84.0) 47(59.5) 女 4(16.0) 32(40.5) 年龄(岁, $\bar x $ ±s)65.7±7.7 59.4±12.1 −2.439 0.016 BMI(kg·m−2, $\bar x $ ±s)22.1±3.1 22.3±3.1 0.333 0.739 基础疾病[n(%)] 10(40.0) 31(39.2) 0.005 1.000 高血压 9(36.0) 26(32.9) 0.081 0.811 糖尿病 5(20.0) 14(17.7) 0.066 0.773 冠心病 3(12.0) 4(5.1) − 0.355 是否进行外科手术[n(%)] 0.562 0.334 是 19(76.0) 65(82.3) 否 6(24.0) 14(17.7) 术前是否有感染1[n(%)] 0.313 0.220 是 5(26.3) 10(15.4) 否 14(73.7) 55(84.6) 利奈唑胺使用时长[n, M(Q1, Q3)] 12(9, 18) 10(7, 13) −2.144 0.032 住院天数[n, M(Q1, Q3)] 45(27, 64) 42(31, 56) −0.377 0.706 联用抗菌药[n(%)] 21(84.0) 72(91.1) 1.023 0.454 血小板计数[×109/L, M(Q1,Q3)] 135(121, 208) 228(172, 304) −3.671 <0.001 血红蛋白[g/L, M(Q1,Q3)] 94(86.5, 106) 99(91, 107) −1.172 0.241 白细胞计数[×109/L, M(Q1,Q3)] 13.91(9.2, 18.5) 9.37(7.2, 12.1) −2.906 0.004 白蛋白(g/L, $\bar x $ ±s)35.2±4.7 35.8±4.6 0.572 0.569 ALT [U/L, M(Q1, Q3)] 85(32, 206) 36(20, 68) −3.413 0.001 AST [U/L, M(Q1, Q3)] 69(36.5, 69) 33(21, 41) −4.029 <0.001 总胆红素[μmol/L, M(Q1, Q3)] 49.1(23.9, 112.3) 27.3(17.5, 57.7) −2.267 0.023 肌酐[μmol/L, M(Q1, Q3)] 69(56, 132) 57(45, 75) −2.834 0.005 肾小球滤过率[ml/min, $\bar x $ ±s]93.1±39.3 118.8±46.4 2.500 0.014 注1:比较两组接受外科手术的患者术前感染情况,血小板减少组(n=19),未发生组(n=65)。 表 2 利奈唑胺相关性血小板减少的危险因素
变量 回归系数 标准误 统计量 OR P值 95%CI 年龄≥60岁 1.959 0.819 5.716 7.093 0.017 1.423~35.341 利奈唑胺使用时长≥12 d 1.481 0.703 4.437 4.399 0.035 1.108~17.455 血小板计数≤200×109/L 2.137 0.738 8.380 8.470 0.004 1.994~35.986 基础AST≥50 U/L 2.739 0.756 13.114 15.465 <0.001 3.513~68.085 基础白细胞计数≥11×109/L 2.437 0.755 10.420 11.436 0.001 2.605~50.217 -
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