儿童革兰阴性菌血流感染的流行病学及细菌耐药特征

Characteristics of epidemiology and antimicrobial resistance of gram-negative bacterial bloodstream infections in children

目的 了解儿童革兰阴性菌血流感染的流行病学及细菌耐药性特征和变迁.方法 回顾性分析2010年1月-2015年12月温州医科大学附属育英儿童医院收治的399例革兰阴性菌血流感染患儿的临床资料、细菌学及药敏试验结果.结果 男253例,女146例,年龄16 h ～ 16岁,中位年龄10.1月龄.261例（65.4％）来自新生儿科,儿童重症监护病房31例（7.8％）,消化科29例（7.3％）.275例（68.9％）有基础疾病,包括早产儿172例,新生儿呼吸窘迫综合征67例,新生儿窒息53例.80例接受侵入性操作,20例有外科手术史.社区获得性感染149例（37.3％）,医院获得性感染250例（62.7％）.50例发生严重并发症：感染性休克40例,多器官功能障碍综合征32例,弥漫性血管内凝血7例.治愈288例,好转48例,未愈放弃治疗17例,死亡46例（11.5％）.399例中检出408株革兰阴性菌,肠杆菌科细菌346株（84.8％）;非发酵菌49株（12.0％）,其他革兰阴性菌13株（3.2％）.大肠埃希菌（175株）和肺炎克雷伯菌（106株）对碳青霉烯类抗生素、β内酰胺类加酶抑制剂、阿米卡星、头孢西丁的耐药率均低于10.0％.共检出多重耐药菌245株（60.1％）,其中肠杆菌科细菌225株,非发酵菌18株.检出9株耐碳青霉烯类抗生素肠杆菌科细菌,对阿米卡星全部敏感,对喹诺酮类的敏感率为88.9％,5株检测对替加环素的药敏,结果均敏感.2013-2015年与2010-2012年比较,克雷伯菌属在革兰阴性菌中的占比分别为32.9％和21.2％;大肠埃希菌和肺炎克雷伯菌对β内酰胺类加酶抑制剂、碳青霉烯类抗生素、阿米卡星的耐药率无明显变化.结论 革兰阴性菌血流感染好发于新生儿期,多数伴基础疾病.大肠埃希菌和肺炎克雷伯菌为主要致病菌,β内酰胺类加酶抑制剂和碳青霉烯类抗生素可作为重症肠杆菌科细菌血流感染治疗的经验性选择.

Objective To study the epidemiology and antimicrobial resistance of Gram-negative bacterial bloodstream infections in children,and to guide the choice of antimicrobials and the control of nosocomial infection.Method Clinical data,bacteriology and antimicrobial susceptibility test results were collected retrospectively in hospitalized children who were diagnosed with gram-negative bacterial bloodstream infections in Yuying Children＆#39;s Hospital of Wenzhou Medical University from January,2010 to December,2015.Result A total of 399 cases （253 male and 146 female） were identified.The age ranged from 16 hours to 16 years （median age 10.1 months）.The majority of cases were collected from division of neonatology （n =261,65.4%）,followed by 31 cases （7.8%） from pediatric intensive care unit and 29 cases （7.3%） from Gastroenterology Department;275 cases （68.9%） had underlying diseases,mainly including preterm birth（n =172）,neonatal respiratory distress syndrome（n =67） and newborn asphyxia（n =53）.Eighty cases had received invasive procedures and 20 had surgical operation;149 cases （37.3%） were community-acquired and 250 cases （62.7%） were hospital acquired.Fifty cases had complications.among those,40 cases had septic shock,32 cases had multiple organ dysfunction syndrome and 7 cases had disseminated intravascular coagulation;288 cases were cured,48 improved,17 gave up treatment and discharged,and 46 died;totally 408 strains were isolated from 399 children,including Enterobacteriaceae （346,84.8%）,non-fermentative Gram-negative bacteria （49,12.0%） and other gram-negative bacteria （13,3.2%）.The resistance rates of Escherichia coli （n =175） and Klebsiella pneumoniae （n =106） to carbapenems,β-lactams enzyme and its inhibitors,amikacin and cefoxitin were all lower than 10%.Totally 245 multi-drug resistant strains （60.1%） were isolated,including 225 strains of Enterobacteriaceae and 18 strains of non-fermentative Gram-negative bacteria （P 〈 0.01）.Nine strains of Carbapenem-resistant Enterobacteriaceae were isolated,which were all sensitive to amikacin and the sensitive rates to fluoroquinolone reached 88.9%.Five strains which were detected sensitive to tigecycline were all sensitive.The proportion of Klebsiella sp in Gram-negative bacteria between 2013-2015 and 2010-2012 were 32.9% and 21.2%,respectively.The resistance rates of Escherichia coli and Klebsiella pneumoniae to β-lactams and its enzyme inhibitors and carbapenems had no significant change.Conclusion Gramnegative bacterial bloodstream infections occur more frequently in newborns.Most children had combined underlying diseases.Escherichia coli and Klebsiella pneumoniae are the most common pathogens.β-Lactams and its enzyme inhibitors and carbapenems are the empirical choice of antimicrobial therapy for severe Enterobacteriaceae bloodstream bacterial infections.