儿童急性白血病多重耐药菌血流感染的临床特征和高危因素分析
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摘要
目的探讨急性白血病患儿合并多重耐药菌(MDR)血流感染的临床特征及高危因素。方法回顾性分析2013年1月1日至2018年9月30日期间南方医科大学珠江医院儿科收治的121例合并细菌性血流感染的急性白血病患儿的临床资料,根据Magiorakos等专家2012年提出的MDR、泛耐药(XDR)、全耐药(PDR)术语国际标准化建议判定MDR株,将其分为MDR组与非多重耐药菌(non-MDR)组进行对比分析。结果 121例合并细菌性血流感染的急性白血病患儿中,MDR组55例,non-MDR组66例。MDR组中革兰阳性菌31株,前3位依次为凝固酶阴性葡萄球菌、金黄色葡萄球菌以及缓症链球菌;革兰阴性菌则以大肠埃希菌为主。Logistic分析提示MDR血流感染好发于急性髓系白血病患儿(P=0.038;OR 2.505;95%CI 1.036～6.058),常见于诱导化疗阶段(P=0.038;OR 2.226;95%CI1.045～4.774),发热前中性粒细胞缺乏时间>7 d(P=0.003;OR 3.36;95%CI 1.520～7.428)、血红蛋白<70 g/L(P=0.122;OR 1.897;95%CI 0.842～4.274)及血小板<20 g/L(P=0.005;OR 2.995;95%CI 1.388～6.464)为MDR血流感染的高危因素。MDR组发热时长和抗生素疗程均长于non-MDR组,MDR组的降钙素原与C反应蛋白均高于nonMDR组。MDR组的初始经验性治疗有效率较低,重症监护病房转入率与病死率都更高。结论急性髓系白血病、诱导化疗、发热前中性粒细胞缺乏时间>7 d、血红蛋白<70 g/L以及血小板<20×109/L是白血病患儿出现MDR血流感染的危险因素。MDR血流感染炎症反应重,可能导致更长的抗感染疗程以及较差的预后。
Objective To investigate the clinical features and risk factors of multidrug-resistant bloodstream infection in children with acute leukemia. Methods The clinical data of 121 blood culture-positive patients with acute leukemia admitted from January 1,2013 to September 30,2018 to Department of Pediatrics,Zhujiang Hospital of Southern Medical University were analyzed retrospectively. Results Of the 121 patients with acute leukemia infected with bacterial bloodstream,55 were in the multidrug-resistant(MDR)group and 66 in the non-multidrug-resistant(non-MDR)group. There were 31 grampositive bacteria in the MDR group. The top three strains were coagulase-negative Staphylococci,Staphylococcus aureus and Streptococcus mutans. Escherichia coli was the main strain of gram-negative bacteria. Logistic analysis suggested that MDR bloodstream infection was more likely to occur in the patiens with AML(P=0.038;OR 2.505;95%CI 1.036—6.058)and at induction chemotherapy stage(P=0.038;OR 2.226;95%CI 1.045—4.774). Other high-risk factors included neutropenic dysplasia >7 d before fever(P=0.003;OR 3.36;95%CI 1.520—7.428),hemoglobin <70 g/L(P=0.122;OR 1.897;95%CI0.842—4.274),and platelet<20 g/L(P=0.005;OR 2.995;95%CI 1.388—6.464). The fever duration and antibiotic course in the MDR group were longer than those in the non-MDR group,and the procalcitoni and C-reactive protein were higher in the MDR group. The empirical treatment of the MDR group was less effective,and the transfer rate for ICU and mortality rate were higher. Conclusion AML,induction chemotherapy,neutrophil deficiency time before fever >7 days,hemoglobin<70 g/L and platelet<20×109/L are risk factors for MDR bloodstream infection. The inflammation response is severe MDR bloodstream infections,which may result in longer anti-infective treatments and a worse prognosis.
Objective To investigate the clinical features and risk factors of multidrug-resistant bloodstream infection in children with acute leukemia. Methods The clinical data of 121 blood culture-positive patients with acute leukemia admitted from January 1,2013 to September 30,2018 to Department of Pediatrics,Zhujiang Hospital of Southern Medical University were analyzed retrospectively. Results Of the 121 patients with acute leukemia infected with bacterial bloodstream,55 were in the multidrug-resistant(MDR)group and 66 in the non-multidrug-resistant(non-MDR)group. There were 31 grampositive bacteria in the MDR group. The top three strains were coagulase-negative Staphylococci,Staphylococcus aureus and Streptococcus mutans. Escherichia coli was the main strain of gram-negative bacteria. Logistic analysis suggested that MDR bloodstream infection was more likely to occur in the patiens with AML(P=0.038;OR 2.505;95%CI 1.036—6.058)and at induction chemotherapy stage(P=0.038;OR 2.226;95%CI 1.045—4.774). Other high-risk factors included neutropenic dysplasia >7 d before fever(P=0.003;OR 3.36;95%CI 1.520—7.428),hemoglobin <70 g/L(P=0.122;OR 1.897;95%CI0.842—4.274),and platelet<20 g/L(P=0.005;OR 2.995;95%CI 1.388—6.464). The fever duration and antibiotic course in the MDR group were longer than those in the non-MDR group,and the procalcitoni and C-reactive protein were higher in the MDR group. The empirical treatment of the MDR group was less effective,and the transfer rate for ICU and mortality rate were higher. Conclusion AML,induction chemotherapy,neutrophil deficiency time before fever >7 days,hemoglobin<70 g/L and platelet<20×109/L are risk factors for MDR bloodstream infection. The inflammation response is severe MDR bloodstream infections,which may result in longer anti-infective treatments and a worse prognosis.
引文
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[11]张交生,董意妹,郑跃杰,等.不同年龄发热患儿血培养阳性菌株分布及其耐药性分析[J].中国实用儿科杂志,2016,31(3):215-218.
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[13]中华人民共和国卫生部.医院感染诊断标准[J].中华医学杂志,2001,81(5):315-320.
[14]Magiorakos AP,Srinivasan A,Carey RB,et al.Multidrug-resistant,extensive drug-resistant and pandrug-resistant bacteria:an international expert proposal for interim standard definitions for acquired resistance[J].Clin Microbiol Infect,2012,18(3):268-281.
[15]中华医学会血液学分会,中国医师协会血液科医师分会.中国中性粒细胞缺乏伴发热患者抗菌药物临床应用指南(2016年版)[J].中华血液学杂志,2016,12(5):353-359.
[16]Averbuch D,Orasch C,Cordonnier C,et al.European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance:summary of the 20114th European Conference on Infections in Leukemia[J].Haematologica,2013,98(12):1826-1835.
[17]Webb BJ,Harrington R,Schwatz J,et al.The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation[J].Transpl Infect Dis,2018,20(5):e12961.
[18]梁利杰,梁华杰,孙慧.急性白血病患者化疗后感染的临床分析[J].中华医院感染学杂志,2014,24(15):3744-3746.
[19]Luo Y,Liu T,Xie S,et al.Clinical features and risk factors for infections in adult acute leukemia after chemotherapy[J].Zhonghua Xue Ye Xue Za Zhi,2015,36(12):1020-1024.
[20]汤丽苑,俞康.血液病粒细胞缺乏患者医院血流感染的回顾性临床分析[J].中华医院感染学杂志,2012,22(23):5241-5243.
[21]Elom MO,Eyo JE,Okafor FC,et al.Improved infant hemoglobin(Hb)and blood glucose concentrations:The beneficial effect of maternal vitamin A supplementation of malaria-infected mothers in Ebonyi State,Nigeria[J].Pathog Glob Health,2017,111(1):45-48.
[22]Wang M,Li H,Si J,et al.Amniotic fluid-derived stem cells mixed with platelet rich plasma for restoration of rat alveolar bone defect[J].Acta Biochim Biophys Sin(Shanghai),2017,49(3):197-207.
[23]Ahmed M,Reffat SA,Hassan A,et al.Platelet-rich plasma for the treatment of clean diabetic foot ulcers[J].Ann Vasc Surg,2017,38:206-211.
[24]Krijgsveld J,Zaat SA,Meeldijk J,et al.Thrombocidins,microbicidal proteins from human blood platelets,are C-terminal deletion products of CXC chemokines[J].J Biol Chem,2000,275(27):20374-20381.
[25]Arman M,Krauel K,Tilley DO,et al.Amplification of bacteria-induced platelet activation is triggered by FcγRIIA,integrinαIIbβ3,and platelet factor 4[J].Blood,2014,123(20):3166-3174.
[26]Czapiga M,Gao JL,Kirk A,et al.Human platelets exhibit chemotaxis using functional N-formyl peptide receptors[J].Exp Hematol,2005,33(1):73-84.
[27]张国扬,杨鹏凤,王秀菊,等.血液病住院患者血流感染死亡危险因素分析[J].中山大学学报(医学科学版),2017,38(4):622-627.
[28]Bergmann K,Hasle H,Asdahl P,et al.Central venous catheters and bloodstream infection during induction therapy in children with acute lymphoblastic leukemia[J].J Pediatr Hematol Oncol,2016,38(3):e82-87.
[29]胡付品,郭燕,朱德妹,等.2017年CHINET中国细菌耐药性监测[J].中国感染与化疗杂志,2018,18(3):241-251.
[30]阮永胜,李春富,何岳林,等.儿童急性髓性白血病强烈化疗粒细胞缺乏期预防性应用抗生素临床疗效研究[J].中国实用儿科杂志,2013,28(8):594-597.
[31]Hussein AA,Al-Antary ET,Najjar R,et al.Incidence and risk factors of bacterial infections in children following autologous hematopoietic stem cell transplantation:Single-center experience from Jordan[J].Pediatr Transplant,2016,20(5):683-686.
[2]吴沪军,温顺航,张渊博,等.住院患儿血流感染586例病原菌分布及耐药性分析[J].中国实用儿科杂志,2015,30(6):431-435.
[3]Wang TY,Li ZJ,Lin QS,et al.Clinical and bacteriological analysis of lymphoid tissue neoplasms patients with bacteriabloodstream infections.[J].Zhong Hua Xue Ye Xue Za Zhi,2017,38(12):1043-1048.
[4]Caldas TD,Martins ODL,Orlandi MPH,et al.Infection surveillance in pediatric hematopoietic stem cell transplantation recipients[J].Eur J Haematol,2018,100(1):69-74.
[5]Li MJ,Chang HH,Yang YL,et al.Infectious complications in children with acute lymphoblastic leukemia treated with the Taiwan Pediatric Oncology Group protocol:A 16-year tertiary single-institution experience[J].Pediatr Blood Cancer,2017,64(10).
[6]Yao JF,Li N,Jiang J.Clinical characteristics of bloodstream infections in pediatric acute leukemia:A single-center experience with 231 patients[J].Chin Med J(Engl),2017,130(17):2076-2081.
[7]Kato H,Fujita H,Akiyama N,et al.Infectious complications in adults undergoing intensive chemotherapy for acute myeloid leukemia in 2001-2005 using the Japan Adult Leukemia Study Group AML201 protocols[J].Support Care Cancer,2018,26(12):4187-4198.
[8]Maham S,Fallah F,Gholinejad Z,et al.Bacterial etiology and antibiotic resistance pattern of pediatricbloodstream infections:A multicenter based study in Tehran,Iran[J].Ann lg,2018,30(4):337-345.
[9]李光辉,朱德妹,汪复,等.2012年中国CHINET血培养临床分离菌的分布及耐药性[J].中国感染与化疗杂志,2014,14(6):474-481.
[10]谭惠珍,刘艳薇,黄礼彬,等.化疗后粒细胞缺乏住院患儿612例次发热原因分析[J].中国实用儿科杂志,2013,28(11):848-850.
[11]张交生,董意妹,郑跃杰,等.不同年龄发热患儿血培养阳性菌株分布及其耐药性分析[J].中国实用儿科杂志,2016,31(3):215-218.
[12]张之南,沈悌.血液病诊断及疗效标准[M].3版.北京:科学出版社,2007:103-121.
[13]中华人民共和国卫生部.医院感染诊断标准[J].中华医学杂志,2001,81(5):315-320.
[14]Magiorakos AP,Srinivasan A,Carey RB,et al.Multidrug-resistant,extensive drug-resistant and pandrug-resistant bacteria:an international expert proposal for interim standard definitions for acquired resistance[J].Clin Microbiol Infect,2012,18(3):268-281.
[15]中华医学会血液学分会,中国医师协会血液科医师分会.中国中性粒细胞缺乏伴发热患者抗菌药物临床应用指南(2016年版)[J].中华血液学杂志,2016,12(5):353-359.
[16]Averbuch D,Orasch C,Cordonnier C,et al.European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance:summary of the 20114th European Conference on Infections in Leukemia[J].Haematologica,2013,98(12):1826-1835.
[17]Webb BJ,Harrington R,Schwatz J,et al.The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation[J].Transpl Infect Dis,2018,20(5):e12961.
[18]梁利杰,梁华杰,孙慧.急性白血病患者化疗后感染的临床分析[J].中华医院感染学杂志,2014,24(15):3744-3746.
[19]Luo Y,Liu T,Xie S,et al.Clinical features and risk factors for infections in adult acute leukemia after chemotherapy[J].Zhonghua Xue Ye Xue Za Zhi,2015,36(12):1020-1024.
[20]汤丽苑,俞康.血液病粒细胞缺乏患者医院血流感染的回顾性临床分析[J].中华医院感染学杂志,2012,22(23):5241-5243.
[21]Elom MO,Eyo JE,Okafor FC,et al.Improved infant hemoglobin(Hb)and blood glucose concentrations:The beneficial effect of maternal vitamin A supplementation of malaria-infected mothers in Ebonyi State,Nigeria[J].Pathog Glob Health,2017,111(1):45-48.
[22]Wang M,Li H,Si J,et al.Amniotic fluid-derived stem cells mixed with platelet rich plasma for restoration of rat alveolar bone defect[J].Acta Biochim Biophys Sin(Shanghai),2017,49(3):197-207.
[23]Ahmed M,Reffat SA,Hassan A,et al.Platelet-rich plasma for the treatment of clean diabetic foot ulcers[J].Ann Vasc Surg,2017,38:206-211.
[24]Krijgsveld J,Zaat SA,Meeldijk J,et al.Thrombocidins,microbicidal proteins from human blood platelets,are C-terminal deletion products of CXC chemokines[J].J Biol Chem,2000,275(27):20374-20381.
[25]Arman M,Krauel K,Tilley DO,et al.Amplification of bacteria-induced platelet activation is triggered by FcγRIIA,integrinαIIbβ3,and platelet factor 4[J].Blood,2014,123(20):3166-3174.
[26]Czapiga M,Gao JL,Kirk A,et al.Human platelets exhibit chemotaxis using functional N-formyl peptide receptors[J].Exp Hematol,2005,33(1):73-84.
[27]张国扬,杨鹏凤,王秀菊,等.血液病住院患者血流感染死亡危险因素分析[J].中山大学学报(医学科学版),2017,38(4):622-627.
[28]Bergmann K,Hasle H,Asdahl P,et al.Central venous catheters and bloodstream infection during induction therapy in children with acute lymphoblastic leukemia[J].J Pediatr Hematol Oncol,2016,38(3):e82-87.
[29]胡付品,郭燕,朱德妹,等.2017年CHINET中国细菌耐药性监测[J].中国感染与化疗杂志,2018,18(3):241-251.
[30]阮永胜,李春富,何岳林,等.儿童急性髓性白血病强烈化疗粒细胞缺乏期预防性应用抗生素临床疗效研究[J].中国实用儿科杂志,2013,28(8):594-597.
[31]Hussein AA,Al-Antary ET,Najjar R,et al.Incidence and risk factors of bacterial infections in children following autologous hematopoietic stem cell transplantation:Single-center experience from Jordan[J].Pediatr Transplant,2016,20(5):683-686.