摘要
目的了解儿科重症监护病房(PICU)鲍曼不动杆菌(AB)的耐药状况及耐药基因表达。方法回顾性分析2014年1月至2018年12月中国医科大学附属盛京医院PICU患儿临床分离的311株菌株耐药性,根据耐药检测结果分为耐碳青霉烯鲍曼不动杆菌(CRAB)组和非CRAB组;选取与CRAB密切相关基因进行实时定量(RT)-PCR检测,采用t检验、MannWhitney U检验、χ^(2)检验或Fisher确切检验进行组间对照分析。多元Logistic回归分析进行多因素分析。结果311株菌株对应166例患儿(男101例、女65例),年龄范围为1月龄至14岁。重症支气管肺炎[66例(39.8%)]、中枢神经系统感染[28例(16.9%)]、外伤[17例(10.2%)]是常见的原发病。药物敏感性试验分析提示,AB对替加环素敏感度最高(280/311,90.0%),阿米卡星(250/311,80.4%)及头孢哌酮舒巴坦(193/311,62.1%)随后。但多数AB对环丙沙星(247/311,79.4%)、氨苄西林(244/311,78.5%)和头孢他啶(245/311,78.8%)具有耐药性。311株菌株中有82.6%(257/311)为CRAB,65.9%(205/311)为多重耐药鲍曼不动杆菌(MDRAB)。CRAB组培养AB前碳青霉烯类药物使用率、三代头孢使用≥7 d、其他广谱抗菌药物使用率、联合使用抗菌药物率及介入性操作概率均高于非CRAB组[26.2%(34/130)比8.3%(3/36)、43.8%(57/130)比22.2%(8/36)、47.7%(62/130)比13.9%(5/36)、46.9%(61/130)比22.2%(8/36)、75.4%(98/130)比50.0%(18/36),χ^(2)=5.169、5.533、13.383、7.082、8.631,P=0.023、0.019、<0.01、0.008、0.003];多因素Logistic回归分析提示培养AB前碳青霉烯类抗菌药物使用(OR=3.179,95%CI 1.247~8.107,P=0.015)和介入性操作(OR=5.107,95%CI 1.446~18.042,P=0.011)为CRAB产生的独立危险因素。IPM、OXA-24基因在CRAB和非CRAB中均有表达,差异均无统计学意义[89.2%(116/130)和86.1%(31/36)、77.7%(101/130)和72.2%(26/36),均P>0.05];而VIM及OXA-58基因在两组中未检测到。β-内酰胺酶相关基因OXA-23、OXA-51及外排泵相关基因AdeA、B、C、F、G、H在CRAB中表达率均明显高于非CRAB(均P<0.01)。结论在PICU临床总检出AB中,CRAB和MDRAB所占比例高;仅对替加环素、阿米卡星、头孢哌酮舒巴坦敏感度较高。碳青霉烯类抗菌药物暴露及介入性操作是CRAB菌株产生的独立危险因素。与非CRAB相比CRAB存在高表达β-内酰胺酶相关基因OXA-23和OXA-51及外排泵相关基因AdeA、B、C、F、G、H。
Objective To investigate the drug resistance and related gene expression of Acinetobacter baumannii(AB)among the patients in pediatric intensive care unit(PICU).Methods Drug resistance of 311 clinical cultured AB strains in PICU of Shengjing Hospital of China Medical University between January 2014 to December 2018 were analyzed retrospectively.According to the results of drug resistance test,all strains were divided into carbapenem-resistant Acinetobacter baumannii(CRAB)and non-carbapenem-resistant Acinetobacter baumannii(non-CRAB).The CRAB closely related genes were tested by real time quantitative polymerase chain reaction(RT-PCR).Comparison between the groups was analyzed by t test,Mann-Whitney U test,Chi-square test or Fisher exact test.Multivariate logistic regression was used for multivariate statistics.Results A total of 166 patients with 311 AB strains were enrolled in this research,including 101 males and 65 females.The children′s age ranged from 1 month to 14 years.The main primary diseases of 166 children were severe pneumonia(66/166,39.8%),central nervous system infection(28/166,16.9%),and trauma(17/166,10.2%).Drug sensitivity tests showed that AB was sensitive to tigecycline(280/311,90.0%),amikacin(250/311,80.4%),and cefoperazone-sulbactam(193/311,62.1%).However,most of AB strains were resistant to ciprofloxacin(247/311,79.4%),ampicillin(244/311,78.5%),and ceftazidime(245/311,78.8%).In 311 isolated strains,82.6%(257/311)strains were CRAB,and 65.9%(205/311)strains were multidrug-resistant Acinetobacter baumannii(MDRAB).Carbapenems were used more often in CRAB group than non-CRAB group before Acinetobacter baumannii cultured(26.2%(34/130)vs.8.3%(3/36),χ^(2)=5.169,P=0.023),and more patients in CRAB group used the third-generation cephalosporins for more than 7 days(43.8%(57/130)vs.22.2%(8/36),χ^(2)=5.533,P=0.019).Other broad-spectrum antibiotics or combined antibiotics in CRAB group were also more frequently used than in non-CRAB group(47.7%(62/130)vs.13.9%(5/36),46.9%(61/130)vs.22.2%(8/36);χ^(2)=13.383,7.082;P<0.01,P=0.008).More patients in CRAB group received interventional procedures than those in non-CRAB group(75.4%(98/130)vs.50.0%(18/36),χ²=8.631,P=0.003).Multivariate logistic regression showed that using carbapenem antibiotics(OR=3.179,95%CI 1.247-8.107,P=0.015)and interventional procedures(OR=5.107,95%CI 1.446-18.042,P=0.011)were independent risk factors for causing CRAB.Both IPM and OXA-24 genes had high expressions in CRAB and non-CRAB groups(89.2%(116/130)vs.86.1%(31/36),P=0.565;77.7%(101/130)vs.72.2%(26/36),P=0.49).VIM and OXA-58 genes were not detected in any group.The expression rates of OXA-23,OXA-51,and efflux pump-related genes AdeABC and AdeFGH in CRAB group were significantly higher than in non-CRAB group(all P<0.01).Conclusions In PICU,the proportions of CRAB and MDRAB were high and most of AB strains are only sensitive to tigecycline,amikacin,cefoperazone or sulbactam.Using carbapenems and interventional operation are independent risk factors for causing CRAB.Compared with non-CRAB,CRAB had higher expression ofβ-lactamase-related genes OXA-23 and OXA-51,and efflux pump-related genes AdeABC and AdeFGH.
作者
许彩芳
许巍
Xu Caifang;Xu Wei(Department of Pediatrics,Shengjing Hospital of China Medical University,Shenyang 110004,China)
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2021年第8期651-657,共7页
Chinese Journal of Pediatrics
基金
国家自然科学基金(81771621)
辽宁省重点研发指导计划(2019JH8/10300023)。
