Clinical analysis of early Klebsiella pneumoniae infection after liver transplantation
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摘要:
目的 探究肝移植术后早期肺炎克雷伯菌(KP)感染及其对预后的影响。 方法 回顾性分析171例肝移植受者的资料,根据术后2周细菌培养结果分为无感染组(n=52)和感染组(n=119);感染组86例未检出KP(非KP感染组),33例培养出KP(KP感染组)。比较无感染组和感染组、非KP感染组和KP感染组受者术前、术中及术后资料,分析肝移植术后早期KP感染的危险因素及受者长期生存的影响因素。 结果 与无感染组比较,感染组术前终末期肝病模型(MELD)评分和总胆红素水平高,手术时间、术后重症监护室(ICU)治疗时间及住院时间长,术中红细胞输注量多,住院费用高,严重并发症发生率高,术后14 d和30 d白细胞计数、中性粒细胞绝对数、中性粒细胞与淋巴细胞比值高,术后14 d淋巴细胞绝对数低,术后30 d血红蛋白低,差异均有统计学意义(均为P<0.05)。与非KP感染组比较,KP感染组MELD评分、总胆红素、天冬氨酸转氨酶(AST)水平高,手术时间、术后ICU治疗时间长,住院费用高,术后90 d病死率高,术后14 d白蛋白低,术后30 d总胆红素高,差异均有统计学意义(均为P<0.05)。33例KP感染受者中,16例对碳青霉烯类抗生素耐药,其中7例在术后90 d内死亡;17例对碳青霉烯类抗生素中介或敏感,4例在术后90 d内死亡。术前MELD评分≥17分、手术时间>415 min是肝移植术后KP感染的独立危险因素(均为P<0.05)。术后ICU治疗时间≥44 h和KP感染是肝移植长期预后的独立危险因素(均为P<0.05)。 结论 KP感染是肝移植术后死亡的独立危险因素,术前MELD评分高和手术时间长是肝移植术后早期KP感染的独立危险因素。 Abstract: To identify early Klebsiella pneumoniae (KP) infection after liver transplantation and its impact on prognosis.Methods Clinical data of 171 liver transplant recipients were retrospectively analyzed, and they were divided into the non-infection (n=52) and infection groups (n=119) according to the bacterial culture results at postoperative 2 weeks. In the infection group, KP was not detected in 86 cases (non-KP infection group), and KP was cultured in 33 cases (KP infection group). Preoperative, intraoperative and postoperative data were statistically compared between the non-infection and infection groups, and between the non-KP infection and KP infection groups. The risk factors of early KP infection after liver transplantation and the influencing factors of long-term survival of the recipients were analyzed. Results Compared with the non-infection group, model for end-stage liver disease (MELD) score and total bilirubin level were higher, the operation time was longer, the length of postoperative intensive care unit (ICU) stay and the length of hospital stay were longer, the amount of intraoperative red blood cell transfusion was higher, the hospitalization expense was higher, the incidence of severe complications was higher, white blood cell count, absolute neutrophil cell count and neutrophil-to-lymphocyte ratio at postoperative 14 and 30 d were higher, absolute lymphocyte count at postoperative 14 d was lower and hemoglobin level at postoperative 30 d was lower in the infection group. The differences were statistically significant (all P<0.05). Compared with the non-KP infection group, MELD score, total bilirubin level and aspartate aminotransferase (AST) level were higher, the operation time and the length of postoperative ICU stay were longer, the hospitalization expense was higher, the 90-d fatality was higher, the albumin level at postoperative 14 d was lower, and total bilirubin level at postoperative 30 d was higher in the KP infection group. The differences were statistically significant (all P<0.05). Among 33 recipients with KP infection, 16 cases were resistant to carbapenem antibiotics, and 7 of them died within postoperative 90 d. Seventeen cases were intermediate or sensitive to carbapenem antibiotics, and 4 of them died within postoperative 90 d. Preoperative MELD score ≥17 and operation time>415 min were the independent risk factors for KP infection after liver transplantation (both P<0.05). The length of postoperative ICU stay ≥44 h and KP infection were the independent risk factors for long-term prognosis of liver transplantation (both P<0.05). Conclusions KP infection is an independent risk factor for death after liver transplantation. High preoperative MELD score and long operation time are the independent risk factors for early KP infection after liver transplantation. -
表 1 无感染组和感染组受者术前资料比较
Table 1. Comparison of preoperative data of recipients between non-infection group and infection group
变量 无感染组(n=52) 感染组(n=119) 统计值 P值 年龄[M(P25,P75),岁] 49(40,56) 48(38,55) −0.297 0.766 男性[n(%)] 45(87) 89(75) 2.946 0.086 BMI[M(P25,P75),kg/m2] 23(21,25) 22(21,24) −0.581 0.561 MELD评分[M(P25,P75),分] 16(10,23) 19(13,27) −2.011 0.044 血型[n(%)] 2.184 0.535 A型 18(35) 41(34) B型 9(17) 32(27) AB型 4(8) 8(7) O型 21(40) 38(32) 原发病[n(%)] 乙肝肝硬化 27(52) 63(53) 0.015 0.902 肝恶性肿瘤 11(21) 20(17) 0.461 0.497 酒精性肝硬化 4(8) 7(6) 0.197 0.657 自身免疫性肝病 7(13) 20(17) 0.305 0.581 遗传代谢性疾病 3(6) 9(8) 0.178 0.673 实验室指标 白细胞计数[M(P25,P75),×109/L] 3.1(2.4,4.9) 4.2(2.4,6.1) −1.670 0.095 中性粒细胞绝对数[M(P25,P75),×109/L] 2.1(1.4,3.3) 2.3(1.6,4.2) −1.176 0.240 淋巴细胞绝对数[M(P25,P75),×109/L] 0.7(0.4,1.2) 0.76(0.5,1.1) −0.369 0.712 中性粒细胞与淋巴细胞比值 3.0(2.3,5.3) 3.3(2.1,6.0) −0.931 0.352 血红蛋白($\overline x \pm s $,g/L) 106±26 100±27 1.406 0.163 血小板计数[M(P25,P75),×109/L] 55(32,88) 60(32,100) −0.496 0.620 白蛋白($\overline x \pm s $,g/L) 35±10 35±6 0.287 0.774 总胆红素[M(P25,P75),μmol/L] 34(22,99) 56(26,233) −2.158 0.031 ALT[M(P25,P75),U/L] 36(23,56) 39(26,64) −0.817 0.414 AST[M(P25,P75),U/L] 48(34,80) 49(33,94) −0.420 0.674 表 2 非KP感染组和KP感染组受者术前资料比较
Table 2. Comparison of preoperative data of recipients between non KP infection group and KP infection group
变量 非KP感染组(n=86) KP感染组(n=33) 统计值 P值 年龄[M(P25,P75),岁] 49(39,55) 47(36,55) −0.523 0.601 男性[n(%)] 63(73) 26(79) 0.387 0.534 BMI($\overline x \pm s $,kg/m2) 22.7±3.0 22.5±2.9 0.410 0.683 MELD评分($\overline x \pm s $,分) 18.6±8.7 23.1±2.9 −2.650 0.009 血型[n(%)] 2.847 0.416 A型 31(36) 10(30) B型 24(28) 8(24) AB型 7(8) 1(3) O型 24(28) 14(42) 原发病[n(%)] 乙型肝炎肝硬化 47(55) 16(48) 0.364 0.546 肝恶性肿瘤 15(17) 5(15) 0.089 0.765 酒精性肝硬化 5(6) 2(6) 0.003 0.959 自身免疫性肝病 12(14) 8(24) 1.806 0.179 遗传代谢性疾病 7(8) 2(6) 0.147 0.701 实验室指标 白细胞计数[M(P25,P75),×109/L] 3.9(2.3,5.8) 4.6(3.1,6.9) −1.323 0.186 中性粒细胞绝对数[M(P25,P75),×109/L] 2.2(1.4,3.4) 2.8(1.5,5.0) −1.057 0.291 淋巴细胞绝对数[M(P25,P75),×109/L] 0.7(0.5,1.1) 0.7(0.5,1.0) −0.031 0.975 中性粒细胞与淋巴细胞比值[M(P25,P75)] 3.1(2.0,5.7) 4.2(2.1,7.1) −1.107 0.268 血红蛋白($\overline x \pm s $,g/L) 98±26 105±30 −1.112 0.272 血小板计数[M(P25,P75),×109/L] 61(35,102) 53(27,85) −1.207 0.227 白蛋白($\overline x \pm s $,g/L) 35±7 35±6 0.209 0.834 总胆红素[M(P25,P75),μmol/L] 48(22,148) 98(40,375) −2.737 0.006 ALT[M(P25,P75),U/L] 36(26,59) 49(29,88) −1.645 0.100 AST[M(P25,P75),U/L] 47(31,83) 68(46,144) −2.161 0.031 表 3 无感染组和感染组受者术中及术后资料比较
Table 3. Comparison of intraoperative and postoperative data of recipients between non-infection group and infection group
变量 无感染组(n=52) 感染组(n=119) 统计值 P值 手术时间[M(P25,P75),min] 395(344,445) 425(370,490) −22.523 0.012 无肝期[M(P25,P75),min] 54(46,63) 53(49,63) −20.650 0.515 术中出血量[M(P25,P75),mL] 800(425,1 000) 800(500,1500) −21.635 0.102 术中红细胞输注量[M(P25,P75),U] 4.0(0.3,8.0) 6.0(4.0,10.0) −22.213 0.027 术中血浆输注量[M(P25,P75),mL] 1 000(800,1 400) 1050(800,1 800) −21.964 0.050 GRWR[M(P25,P75),%] 2.0(1.8,2.4) 2.1(1.8,2.5) −20.883 0.377 ICU治疗时间[M(P25,P75),h] 35(25,54) 48(32,89) −23.288 0.001 术后住院时间[M(P25,P75),d] 23(18,28) 27(19,38) −22.547 0.011 总住院费用[M(P25,P75),万元] 18(15,21) 22(17,36) −23.929 <0.001 严重并发症[n(%)] 6(12) 35(29) 6.342 0.012 术后30 d死亡[n(%)] 4(8) 9(8) 0.001 0.977 术后90 d死亡[n(%)] 5(10) 19(16) 1.210 0.271 表 4 非KP感染组和KP感染组受者术中及术后资料比较
Table 4. Comparison of intraoperative and postoperative data of recipients between non KP infection group and KP infection group
变量 非KP感染组(n=86) KP感染组(n=33) 统计值 P值 手术时间[M(P25,P75),min] 415(368,480) 460(418,515) −2.394 0.017 无肝期[M(P25,P75),min] 53(49,63) 50(46,61) −1.451 0.147 术中出血量[M(P25,P75),mL] 800(500,1 500) 800(450,1 500) −0.332 0.740 术中红细胞输注量[M(P25,P75),U] 6(4,10) 6(2,10) −0.093 0.926 术中血浆输注量[M(P25,P75),mL] 1 000(800,1 800) 1 400(1 000,2 025) −1.573 0.116 GRWR[M(P25,P75),%] 2.1(1.7,2.5) 2.2(1.8,2.5) −0.671 0.502 ICU治疗时间[M(P25,P75),h] 42(28,68) 79(54,242) −4.723 <0.001 术后住院时间[M(P25,P75),d] 25(19,35) 32(23,41) −1.963 0.050 住院总费用[M(P25,P75),万元] 20(17,29) 28(20,51) −2.659 0.008 严重并发症[n(%)] 25(29) 10(30) 0.017 0.895 术后30 d死亡[n(%)] 5(6) 4(12) 1.357 0.244 术后90 d死亡[n(%)] 8(9) 11(33) 10.265 0.001 表 5 无感染组和感染组受者术后实验室指标比较
Table 5. Comparison of postoperative laboratory indicators of recipients between non-infection group and infection group
指标 无感染组(n=52) 感染组(n=119) 统计值 P值 术后14 d 白细胞计数[M(P25,P75),×109/L] 6(4,9) 9(6,13) −3.926 <0.001 中性粒细胞绝对数[M(P25,P75),×109/L] 4(3,7) 7(5,11) −3.926 <0.001 淋巴细胞绝对数[M(P25,P75),×109/L] 0.8(0.6,1.1) 0.6(0.4,1.0) −2.098 0.036 中性粒细胞与淋巴细胞比值[M(P25,P75)] 6(4,9) 11(8,16) −5.736 <0.001 血红蛋白[M(P25,P75),g/L] 97(88,103) 93(86,103) −0.905 0.366 血小板[M(P25,P75),×109/L] 54(36,102) 64(41,102) −1.424 0.154 白蛋白($\overline x \pm s $,g/L) 38±4 39±4 −0.435 0.664 总胆红素[M(P25,P75),μmol/L] 32(19,68) 35(23,72) −1.195 0.232 ALT[M(P25,P75),U/L] 87(66,151) 96(52,159) −0.031 0.976 AST[M(P25,P75),U/L] 27(17,45) 38(21,64) −1.667 0.093 术后30 d 白细胞计数[M(P25,P75),×109/L] 4(3,5) 5(4,8) −3.938 <0.001 中性粒细胞绝对数[M(P25,P75),×109/L] 2.5(1.8,3.3) 3.7(2.5,5.5) −3.945 <0.001 淋巴细胞绝对数[M(P25,P75),×109/L] 0.7(0.6,1.4) 0.9(0.5,1.3) −0.468 0.640 中性粒细胞与淋巴细胞比值[M(P25,P75)] 3.4(2.0,4.3) 4.3(2.7,7.4) −2.958 <0.001 血红蛋白[M(P25,P75),g/L] 100±19 91±17 2.799 0.006 血小板[M(P25,P75),×109/L] 131(82,193) 136(84,252) −0.817 0.414 白蛋白($\overline x \pm s $,g/L) 40±4 39±4 1.487 0.139 总胆红素[M(P25,P75),μmol/L] 21(13,31) 17(10,28) −1.651 0.099 ALT[M(P25,P75),U/L] 29(15,54) 26(15,43) −0.575 0.565 AST[M(P25,P75),U/L] 23(16,35) 25(15,38) −0.634 0.526 表 6 非KP感染组和KP感染组患者术后实验室检查结果
Table 6. Comparison of postoperative laboratory indicators of recipients between non KP infection group and KP infection group
指标 非KP感染组(n=86) KP感染组(n=33) 统计值 P值 术后14 d 白细胞计数[M(P25,P75),×109/L] 9(7,13) 8(6,13) −0.513 0.608 中性粒细胞绝对数[M(P25,P75),×109/L] 7(5,11) 6(5,11) −0.405 0.686 淋巴细胞绝对数[M(P25,P75),×109/L] 0.7(0.4,1.0) 0.6(0.4,1.0) −0.717 0.474 中性粒细胞与淋巴细胞比值[M(P25,P75)] 11(7,16) 12(8,20) −0.627 0.531 血红蛋白[M(P25,P75),g/L] 96±15 94±16 0.656 0.513 血小板[M(P25,P75),×109/L] 66(46,103) 61(37,100) −1.202 0.229 白蛋白(`x±s,g/L) 39±5 37±3 2.29 0.024 总胆红素[M(P25,P75),μmol/L] 34(23,68) 43(24,112) −1.418 0.156 ALT[M(P25,P75),U/L] 96(57,160) 106(47,161) −0.309 0.757 AST[M(P25,P75),U/L] 38(19,54) 41(26,76) −1.151 0.250 术后30 d 白细胞计数[M(P25,P75),×109/L] 5(4,7) 7(4,9) −1.203 0.229 中性粒细胞绝对数[M(P25,P75),×109/L] 3.5(2.5,4.8) 4.2(2.3,7.1) −0.870 0.384 淋巴细胞绝对数[M(P25,P75),×109/L] 0.9(0.6,1.2) 1.0(0.5,1.3) −0.491 0.623 中性粒细胞与淋巴细胞比值[M(P25,P75)] 4.2(2.8,6.5) 5.2(2.1,8.9) −0.690 0.490 血红蛋白[M(P25,P75),g/L] 92±16 87±19 1.031 0.305 血小板[M(P25,P75),×109/L] 142(92,264) 109(77,222) −1.415 0.157 白蛋白(`x±s,g/L) 39±4 38±5 0.943 0.348 总胆红素[M(P25,P75),μmol/L] 14(10,25) 21(15,35) −2.619 0.009 ALT[M(P25,P75),U/L] 25(15,42) 27(17,46) −0.571 0.568 AST[M(P25,P75),U/L] 24(15,35) 28(17,48) −0.980 0.327 表 7 肝移植术后KP感染的危险因素分析
Table 7. Risk factors analysis of KP infection after liver transplantation
变量 单因素分析 多因素 OR①(95%CI②) β值 P值 OR(95%CI) β值 P值 一般情况 性别(男比女) 1.032(0.408~2.608) 0.031 0.947 年龄(≥49岁比<49岁) 0.888(0.415~1.899) −0.119 0.760 BMI(≥22.49 kg/m2比<22.49 kg/m2) 0.914(0.428~1.955) −0.090 0.817 术前资料 MELD评分(≥17分比<17分) 3.217(1.357~7.627) 1.168 0.008 2.832(1.138~7.048) 1.041 0.025 乙型肝炎病毒感染(罹患比未罹患) 0.726(0.337~1.562) −0.321 0.412 肝恶性肿瘤(罹患比未罹患) 0.763(0.305~1.098) −0.271 0.563 白细胞计数(≥3.78×109/L比<3.78×109/L) 1.348(0.629~2.889) 0.298 0.443 中性粒细胞绝对数(≥2.23×109/L比<2.23×109/L) 1.832(0.844~3.973) 0.605 0.126 淋巴细胞绝对数(≥0.66×109/L比<0.66×109/L) 0.969(0.453~2.071) -0.032 0.935 中性粒细胞与淋巴细胞比值(≥3.12比<3.12) 1.616(0.750~3.480) 0.480 0.220 血红蛋白(≥101.51 g/L比<101.51 g/L) 0.914(0.428~1.955) −0.090 0.817 血小板(≥59×109/L比<59×109/L) 0.833(0.389~1.786) −0.182 0.639 白蛋白(≥35.22 g/L比<35.22 g/L) 0.964(0.449~2.066) −0.037 0.924 ALT(≥39 U/L比<39 U/L) 2.990(1.323~6.756) 1.095 0.008 2.850(0.820~9.901) 1.047 0.099 AST(≥49 U/L比<49 U/L) 2.659(1.178~6.004) 0.978 0.019 1.036(0.296~3.628) 0.035 0.956 术中资料 手术时间(≥415 min比<415 min) 4.295(1.748~10.554) 1.457 0.001 4.370(1.716~11.130) 1.475 0.002 术中出血量(≥800 mL比<800 mL) 0.995(0.443~2.061) −0.046 0.907 术中红细胞输注量(≥4.5 U比<4.5 U) 1.318(0.612~2.838) 0.276 0.480 术中血浆输注量(≥1 000 mL比<1 000 mL) 2.316(0.939~5.710) 0.840 0.068 GRWR(≥2.09%比<2.09%) 1.471(0.686~3.154) 0.386 0.321 注:①OR为比值比。
②CI为可信区间。表 8 肝移植长期预后的危险因素分析
Table 8. Analysis of risk factors for long-term prognosis of liver transplantation
变量 单因素分析 多因素分析 HR①(95%CI②) β值 P值 HR(95%CI) β值 P值 一般资料 性别(男比女) 1.017(0.443~2.337) 0.017 0.968 年龄(≥49岁比<49岁) 0.955(0.487~1.871) −0.046 0.893 BMI(≥22.49 kg/m2比<22.49 kg/m2) 0.847(0.432~1.661) −0.166 0.629 术前资料 MELD评分(≥17分比<17分) 2.207(1.055~4.617) 0.792 0.036 1.467(0.682~3.154) 0.383 0.327 乙型肝炎病毒感染(罹患比未罹患) 1.009(0.505~2.015) 0.009 0.980 肝恶性肿瘤(罹患比未罹患) 1.155(0.539~2.477) 0.144 0.711 术中资料 手术时间(≥415 min比<415 min) 1.684(0.833~3.405) 0.521 0.146 术中出血量(≥800 mL比<800 mL) 1.307(0.647~2.642) 0.268 0.455 GRWR(≥2.09%比<2.09%) 0.896(0.455~1.763) −0.110 0.750 术后资料 ICU治疗时间(≥44 h比<44 h) 4.021(1.751~9.236) 1.392 0.001 2.712(1.089~6.754) 0.998 0.032 感染(是比否) 1.072(0.512~2.242) 0.069 0.854 KP感染(是比否) 3.439(1.734~6.820) 1.235 <0.001 2.145(1.031~4.465) 0.763 0.041 注:①HR为风险比。
②CI为可信区间。 -
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