儿童重症监护病房血液病/恶性肿瘤合并脓毒症患儿病原及耐药分析

Analysis of the distribution characteristics and antibiotic resistance of pathogen in children with hematological disorders and cancers complicated with sepsis in PICU

目的探讨儿童重症监护病房(PICU)血液病/恶性肿瘤合并脓毒症患儿病原分布特点及耐药情况。方法回顾性分析2016年1月至2023年8月中国医科大学深圳市儿童医院PICU住院有明确病原的血液病/恶性肿瘤合并脓毒症患儿的病历资料。根据脓毒症28 d结局分为存活组及死亡组。结果纳入176例患儿,发生脓毒症202次,血流感染144例次(71.3%),肺部感染59例次(29.2%),腹部感染21例次(10.4%),软组织感染9例次(4.5%),神经系统感染9例次(4.5%),泌尿系统感染3例次(1.5%)。共确定病原菌244株,革兰阳性菌74株(30.3%):前3位分别是凝固酶阴性葡萄球菌(21株)、金黄色葡萄球菌(19株)、肺炎链球菌(13株);革兰阴性菌122株(50.0%):前3位分别是肺炎克雷伯菌(33株)、大肠埃希菌(25株)、铜绿假单胞菌(23株);真菌48株(19.7%):前3位分别是热带念珠菌(14株)、白色念珠菌(10株)、曲霉菌属及耶氏肺孢子菌(均为7株)。死亡组患儿的鲍曼不动杆菌、嗜麦芽窄食假单胞菌及铜绿假单胞菌检出比例均高于存活组[9.0%(6/67)比2.3%(4/177),χ^(2)=3.971,P=0.046;9.0%(6/67)比1.1%(2/177),χ^(2)=7.080,P=0.008;16.4%(11/67)比6.8%(12/177),χ^(2)=5.288,P=0.021]。57例患儿标本同时送检培养及宏基因组学二代测序(mNGS)技术测定:25例培养和mNGS均检测出病原;30例mNGS检测阳性但培养阴性;2例培养阳性但mNGS检测阴性。多重耐药菌感染79株(46.8%):革兰阳性菌27株(34.2%)、革兰阴性菌52株(65.8%)。174例次(86.1%)脓毒症患儿在发热24 h内接受了经验性抗感染药物治疗。124例次(61.4%)初始经验性抗生素治疗正确覆盖了感染病原菌种类,40例次(19.8%)未覆盖,10例次(5.0%)覆盖不全。22例次(10.9%)尽管覆盖了病原菌种类,但药敏显示对初始抗生素耐药。51例患儿死亡。结论入住PICU的血液病/恶性肿瘤合并脓毒症病原菌以革兰阴性菌为主,其次为革兰阳性菌和真菌。多重耐药菌感染比例高。早期识别并结合本地区的病原学分布及耐药情况,经验性选择合理抗感染治疗策略,有助于提高救治成功率。

Objective To explore the distribution characteristics and antibiotic resistance of pathogen in children with hematological disorders and cancers complicated with sepsis in pediatric intensive care unit(PICU).Methods The clinical data of children with hematological disorders and cancers complicated with sepsis hospitalized at Shenzhen Children′s Hospital affiliated to China Medical University from January 2016 to August 2023 were retrospectively analyzed.Patients were divided into survival group and death group based on the outcome of sepsis on 28 days after diagnosis.Results A total of 202 sepsis episodes occurred in 176 children were enrolled in this study.Among all,144(71.3%)cases of bloodstream infection,59(29.2%)cases of pulmonary infection,21(10.4%)cases of abdominal infection,9(4.5%)cases of soft tissue infection,9(4.5%)cases of nervous system infection,and 3(1.5%)cases of urinary tract infection.A total of 244 pathogenic strains were identified,in which 74(30.3%)cases were gram-positive bacteria.The top 3 pathogens isolated were Coagulase negative Staphylococcus(21 strains),Staphylococcus aureus(19 strains)and Streptococcus pneumoniae(13 strains).Gram-negative bacteria accounted for 122(50.0%)strains,in which top 3 were Klebsiella pneumonia(33 strains),Escherichia coli(25 strains),and Pseudomonas aeruginosa(23 strains).Fungi comprised 48(19.7%)strains:the top 3 were Candida tropicalis(14 strains),Candida albicans(10 strains),Aspergillus and Pneumocystis jirovecii(7 strains each).The incidence of Acinetobacter baumannii,Stenotrophomonas maltophilia,and Pseudomonas aeruginosa were significantly higher in death group compared to survival group[9.0%(6/67)vs.2.3%(4/177),χ^(2)=3.971,P=0.046;9.0%(6/67)vs.1.1%(2/177),χ^(2)=7.080,P=0.008;16.4%(11/67)vs.6.8%(12/177),χ^(2)=5.288,P=0.021].The samples of 57 cases were simultaneously detected by both culture and metagenomic next-generation sequencing(mNGS).Pathogens were detected in 25 cases by both culture and mNGS.In 30 cases,pathogen detection were mNGS positive but culture negative.Two cases showed positive results only with culture.A total of 79(46.8%)strains were multi-drug resistant bacteria,including 27(34.2%)strains of gram-positive bacteria and 52(65.8%)strains of gram-negative bacteria.A total of 174(86.1%)children with sepsis received empirical anti-infective drugs within 24 hours of fever onset.A total of 124(61.4%)cases were appropriately covered by the initial empirical antibiotics,while 40(19.8%)cases were not adequately covered and 10(5.0%)cases had incomplete coverage.Despite the inclusion of pathogenic in the coverage,resistance to initial antibiotics was observed in 22(10.9%)cases.Fifty-one patients died.Conclusion The predominant pathogens responsible for sepsis in PICU with hematological disorders and cancers is gram-negative bacteria,followed by gram-positive bacteria and fungi.In comparison to healthy children with sepsis,there is a higher incidence of fungal infections among hematological disorders and cancers.The proportion of multi-drug resistant bacteria infection is high.Early identification and combination of local etiological distribution and drug resistance,along with the empirical selection of appropriate anti-infection treatment strategies,can greatly enhance survival rate.