Xu C F, Xu W
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Zhonghua Er Ke Za Zhi. 2021 Aug 2;59(8):651-657. doi: 10.3760/cma.j.cn112140-20210117-00053.
To investigate the drug resistance and related gene expression of (AB) among the patients in pediatric intensive care unit (PICU). 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 (CRAB) and non-carbapenem-resistant (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 test, Mann-Whitney test, Chi-square test or Fisher exact test. Multivariate logistic regression was used for multivariate statistics. 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 (MDRAB). Carbapenems were used more often in CRAB group than non-CRAB group before cultured (26.2% (34/130) 8.3% (3/36), χ²5.169, =0.023), and more patients in CRAB group used the third-generation cephalosporins for more than 7 days (43.8% (57/130) 22.2% (8/36), χ²5.533, =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) 13.9% (5/36), 46.9%(61/130) 22.2%(8/36); χ²13.383, 7.082; <0.01, =0.008). More patients in CRAB group received interventional procedures than those in non-CRAB group (75.4% (98/130) 50.0% (18/36), χ²8.631, =0.003). Multivariate logistic regression showed that using carbapenem antibiotics (=3.179, 95% 1.247-8.107, =0.015) and interventional procedures (=5.107, 95% 1.446-18.042, =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) 86.1% (31/36), =0.565; 77.7% (101/130) 72.2% (26/36), =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 <0.01). 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 of β-lactamase-related genes OXA-23 and OXA-51, and efflux pump-related genes AdeABC and AdeFGH.
探讨儿科重症监护病房(PICU)患者中鲍曼不动杆菌(AB)的耐药性及相关基因表达情况。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 311株临床培养的AB菌株的耐药性。根据药敏试验结果,将所有菌株分为耐碳青霉烯类鲍曼不动杆菌(CRAB)和非耐碳青霉烯类鲍曼不动杆菌(非CRAB)。采用实时定量聚合酶链反应(RT-PCR)检测CRAB的密切相关基因。组间比较采用t检验、Mann-Whitney U检验、卡方检验或Fisher确切概率法。采用多因素logistic回归进行多因素统计分析。本研究共纳入166例携带311株AB菌株的患者,其中男性101例,女性65例。患儿年龄1个月至14岁。166例患儿的主要原发病为重症肺炎(66/166,39.8%)、中枢神经系统感染(28/166,16.9%)和创伤(17/166,10.2%)。药敏试验显示,AB对替加环素(280/311,90.0%)、阿米卡星(250/311,80.4%)和头孢哌酮-舒巴坦(193/311,62.1%)敏感。然而,大多数AB菌株对环丙沙星(247/311,79.4%)、氨苄西林(244/311,78.5%)和头孢他啶(245/311,78.8%)耐药。在311株分离菌株中,82.6%(257/311)为CRAB,65.9%(205/311)为多重耐药鲍曼不动杆菌(MDRAB)。培养前CRAB组使用碳青霉烯类药物的频率高于非CRAB组(26.2%(34/130)对8.3%(3/36),χ² =5.169,P =0.023),CRAB组使用第三代头孢菌素超过7天的患者更多(43.8%(57/130)对22.2%(8/36),χ² =5.533,P =0.019)。CRAB组其他广谱抗生素或联合抗生素的使用频率也高于非CRAB组(47.7%(62/130)对13.9%(5/36),46.9%(61/130)对22.2%(8/36);χ² =13.383,7.082;P均<0.01,P =0.008)。CRAB组接受介入操作的患者多于非CRAB组(75.4%(98/130)对50.0%(18/36),χ² =8.631,P =0.003)。多因素logistic回归显示,使用碳青霉烯类抗生素(β =3.179,95%CI 1.247 - 8.107,P =0.015)和介入操作(β =5.107,95%CI 1.446 - 18.042,P =0.011)是导致CRAB的独立危险因素。IPM和OXA-24基因在CRAB组和非CRAB组均高表达(89.2%(116/130)对86.1%(31/36),P =0.565;77.7%(101/130)对72.2%(26/36),P =0.49)。两组均未检测到VIM和OXA-58基因。CRAB组OXA-23、OXA-51及外排泵相关基因AdeABC和AdeFGH的表达率显著高于非CRAB组(均P<0.01)。在PICU中,CRAB和MDRAB的比例较高,大多数AB菌株仅对替加环素、阿米卡星、头孢哌酮或舒巴坦敏感。使用碳青霉烯类药物和介入操作是导致CRAB的独立危险因素。与非CRAB相比,CRAB中β-内酰胺酶相关基因OXA-23和OXA-51以及外排泵相关基因AdeABC和AdeFGH的表达更高。