[1]欧阳龙,肖亚雄.单宁酸与亚胺培南联合对耐碳青霉烯鲍曼不动杆菌的抑菌及抗生物膜作用的实验研究[J].现代检验医学杂志,2025,40(06):171-175.[doi:10.3969/j.issn.1671-7414.2025.06.031]
　OUYANG Long,XIAO Yaxiong.Experimental Studies on the Bacteriostatic and Anti-Biofilm Effects of Tannic Acid Combination with Imipenem on Carbapenem-Resistant Acinetobacter Baumannii[J].Journal of Modern Laboratory Medicine,2025,40(06):171-175.[doi:10.3969/j.issn.1671-7414.2025.06.031]
点击复制

单宁酸与亚胺培南联合对耐碳青霉烯鲍曼不动杆菌的抑菌及抗生物膜作用的实验研究()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年06期
页码:
171-175
栏目:
论著
出版日期:
2025-11-15

文章信息/Info

Title:
Experimental Studies on the Bacteriostatic and Anti-Biofilm Effects of Tannic Acid Combination with Imipenem on Carbapenem-Resistant Acinetobacter Baumannii
文章编号:
1671-7414（2025）06-171-05
作者:
欧阳龙1，肖亚雄2
1.宜宾市中医医院检验科，四川宜宾 644600;2.宜宾市第一人民医院中心实验室，四川宜宾 644600
Author(s):
OUYANG Long1，XIAO Yaxiong2
1.Department of Clinical Laboratory, Yibin Hospital of Traditional Chinese Medicine, Sichuan Yibin 644600, China;2.Department of Central laboratory, the First People’s Hospital of Yibin, Sichuan Yibin 644600, China
关键词:
单宁酸; 亚胺培南; 耐碳青霉烯鲍曼不动杆菌; 最低抑菌浓度; 生物膜
分类号:
R378；R446.5
DOI:
10.3969/j.issn.1671-7414.2025.06.031
文献标志码:
A
摘要:
目的探究单宁酸与亚胺培南联合应用对耐碳青霉烯鲍曼不动杆菌（CRAB）的体外抑菌活性和抗生物膜作用，为单宁酸联合亚胺培南治疗CRAB感染提供理论依据。方法收集宜宾市第一人民医院2022年5月～12月临床分离的30株非重复的CRAB菌株，通过微量肉汤稀释法检测单宁酸和亚胺培南对CRAB的最低抑菌浓度（MIC），根据联合抑菌浓度指数（FICI）评估药物联合作用效果。通过半定量黏附实验观察亚抑菌浓度药物对生物膜形成的影响。通过扫描电镜观察在药物作用下成熟生物膜微观形态的变化。通过逆转录聚合酶链反应（RT-PCR）检测单宁酸和亚胺培南单用和联用后生物膜相关基因BaP，BfS，OmpA表达量的变化。结果单宁酸和亚胺培南对30株CRAB菌株的MIC范围在32~256?g/ml之间，单宁酸联合亚胺培南FICI值在0.625~1之间，表现为相加作用。与对照组相比，单宁酸联合亚胺培南可以有效抑制生物膜的形成、破坏已成熟生物膜结构，联合用药后菌株生物膜相关基因BaP，BfS，OmpA呈低表达，差异具有统计学意义(t=26.32，79.17，29.22，均P<0.05)。结论对于CRAB，单宁酸与亚胺培南联用表现为相加作用。单宁酸联合亚胺培南的抗生物膜作用可能是通过抑制生物膜相关基因BaP，BfS，OmpA的表达而实现。
Abstract:
Objective To investigate the in vitro bacterial inhibitory activity and biofilm effect of the combination of tannic acid and imipenem on carbapenem-resistant Acinetobacter baumannii (CRAB), and provide a theoretical basis for the treatment of CRAB infections with tannic acid in combination with imipenem. Methods Collected 30 non-duplicated CRAB strains from clinical isolates of the First People’s Hospital of Yibin from May to December 2022. The minimal inhibitory concentration (MIC) of tannic acid and imipenem on CRAB was detected separately by micro broth dilution method, and the effect of drug combina-tion was evaluated according to the fractional inhibitory concentration index (FICI). The effect of sub-inhibitory concentration of drugs on biofilm formation was observed by semi-quantitative adhesion assay. Changes in the microscopic morphology of mature biofilms under the effect of drugs were observed by scanning electron microscopy. Changes in the expression of biofilm-asso-ciated genes BaP, BfS, OmpA were detected by reverse transscription PCR (RT-PCR) after the administration of tannic acid and imipenem alone and in combination. Results The MICs of tannic acid and imipenem against 30 CRAB strains ranged from 32 to 256 ?g/ml, and the FICI values of tannic acid combined with imipenem ranged from 0.625 to 1, which showed additive effects. Compared with the control group, tannic acid combined with imipenem could effectively inhibit the formation of biofilm and destroy the structure of mature biofilm, and the biofilm-related genes of BaP, BfS, OmpA and were expressed at a low level in the strains, and the differences were statistically significant (t=26.32, 79.17, 29.22, all P<0.05). Conclusion For CRAB, tannic acid in combination with imipenem showed additive effects. The anti-biofilm effect of tannic acid in combination with imipenem may be realized by inhibiting the expression of biofilm-related genes BaP, BfS, OmpA.

参考文献/References:

[1] 陈和莉,程林,熊丽蓉,等.重庆市4家三级甲等综合医院2017年至2019年鲍曼不动杆菌检出及耐药情况分析[J].中国药业,2022,31(15):28-32. CHEN H L, CHENG L, XIONG L R, et al. Detection and drug resistance of Acinetobacter baumannii of four grade Ⅲ-A general hospitals in Chongqing from 2017 to 2019[J]. China Pharmaceuticals, 2022, 31(15): 28-32.
[2] 李耘,郑波,薛峰,等.中国细菌耐药监测研究(CARST) 2021~2022年革兰氏阴性菌监测报告[J].中国临床药理学杂志,2023,39(23):3525-3544. LI Y, ZHENG B, XUE F, et al. Antimicrobial suscepti-bility of Gram-negative organisms:results from China Antimicrobial Resistance Surveillance Trial(CARST) program,2021~2022[J]. The Chinese Journal of Clinical Pharmacology, 2023, 39(23): 3525-3544.
[3] 孟千琳,凌保东.泛耐药鲍曼不动杆菌生物被膜形成能力与同源性分析[J].医药导报,2022,41(2):244-247. MENG Q L, LING B D. Analysis of biofilm formation abil-ity and homology of extensively drug-resistant acinetobacter baumannii[J]. Herald of Medicine, 2022, 41(2): 244-247.
[4] 邓国英,杨淑凤,任峰,等.鲍曼不动杆菌碳青霉烯耐药性与生物膜形成及O-甘露糖蛋白相关性研究[J].微生物学杂志,2020,40(2):44-48. DENG G Y, YANG S F, REN F, et al. Reciprocity in drug resistance and biofilm formation as well as O-mannopro-tein in carbapenem resistant Acinetobacter baumannii[J]. Journal of Microbiology, 2020, 40(2): 44-48.
[5] TAMMA P D, AITKEN S L, BONOMO R A, et al. Infectious diseases society of America guidance on the treatment of AmpC β-Lactamase-Producing enterobac-terales, Carbapenem-resistant Acinetobacter baumannii , and Senotrophomonas maltophilia infections[J].Clinical infectious diseases, 2022, 74(12): 2089-2114.
[6] 杜仲业.黄芩苷联合利奈唑胺对金黄色葡萄球菌生物被膜干预作用的体内外研究[D]. 南宁:广西医科大学, 2019. DU Z Y. Intervention of Baicalin combined with linezolid on Staphylococcu saureus biofilm in vitro and in vivo[D]. Nanning: Guangxi Medical University,2019.
[7] 莫梓童.黄绵马酸BB联合抗生素对表皮葡萄球菌生物被膜作用研究[D]. 广州:广东药科大学, 2021. MO Z T. Effect of flavaspidic acid BB combined with antibiotics on Staphylococcus epidermidis biofilm[D]. Guangzhou: Guangdong Pharmaceutical University, 2021.
[8] 尉骁,侯渊博,周铁丽,等.单宁酸对临床菌株的抗菌活性及其对生物膜的影响[J]. 温州医科大学学报,2015, 45(10):709-712. WEI X, HOU Y B, ZHOU T L, et al. Antimicrobial ac-tivity of tannic acid and its effect on bioiflms of clinical isolates[J]. Journal of Wenzhou Medical University, 2015, 45(10): 709-712.
[9] 欧阳龙,肖亚雄.单宁酸与不同配比头孢哌酮钠/舒巴坦钠对耐碳青霉烯鲍曼不动杆菌的体外抑菌作用研究[J].实用临床医药杂志,2023,27(15):104-107. OUYANG L, XIAO Y X. In vitro antibacterial roles of carbape-nem-resistant Acinetobacter baumannii by tannic acid and differ-ent cefoperazone sodium-to-sulbactam sodium ratios[J]. Journal of Clinical Medicine in Practice, 2023, 27(15): 104-107.
[10] SOMBORO A M, OSEI SEKYERE J, AMOAKO D G, et al. In vitro potentiation of carbapenems with tannic acid against carbapenemase-producing Enterobacteriaceae: exploring nat-ural products as potential carbapenemase inhibitors[J]. Journal of Applied Microbiology, 2019, 126(2): 452-467.
[11] 丁丽,陈佰义,李敏,等.碳青霉烯类耐药革兰阴性菌联合药敏试验及报告专家共识[J].中国感染与化疗杂志,2023,23(1):80-90. DING L, CHEN B Y, LI M, et al. Expert consensus on antimicrobial synergy testing and reporting of carbap-enemresistant Gram-negative bacteria[J]. Chinese Jour-nal of Infection and Chemotherapy, 2023, 23(1): 80-90.
[12] 尚翔,白会会,刘朝晖.两性霉素B对假丝酵母菌与乳杆菌生物膜作用的研究[J].中国医药导报,2023,20 (16):4-10. SHANG X, BAI H H, LIU Z H. Study on the effect of amphotericin B on the biofilm of Candida and Lactoba-cillus[J]. China Medical Herald, 2023, 20(16): 4-10.
[13] 刘力娟,马立艳,孙伟,等.盐酸小檗碱对耐碳青霉烯类鲍曼不动杆菌生物膜的作用[J].临床检验杂志,2022,40(8):589-594. LIU L J, MA L Y, SUN W, et al. Effects of berberine hydrochloride on biofilm of carbapenem resistant Acinetobacter baumannii [J]. Chinese Journal of Clini-cal Laboratory Science, 2022, 40(8): 589-594.
[14] 戚丽华.鲍曼不动杆菌耐药特性及其与生物膜的相关性研究[D].北京:中国人民解放军军事科学院军事医学研究院,2016. QI L H. Antibiotic resistance profile and its relationship with biofilm formation in Acinetobacter Baumannii[D]. Beijing: Academy of Military Medical Sciences, 2016.
[15] YANG C H, SU P W, MOI S H, et al. Biofilm forma-tion in acinetobacter baumannii: genotype-phenotype correlation[J]. Molecules, 2019, 24(10): 1849.
[16] 郑杨.黄芩素联合美罗培南对耐碳青霉烯鲍曼不动杆菌体外抑菌作用及机制研究[D]. 贵州遵义:遵义医科大学,2021. ZHENG Y. Study on the Mechanism of antibacterial effect in vitro of carbapenem-resistant Acinetobacter baumannii by the combination of baicalein and meropen-em[D]. Guizhou Zunyi: Zunyi Medical University, 2021.
[17] 潘蓓珍,刘岩,宿建胜,等.耐碳青霉烯类鲍曼不动杆菌生物膜形成与外排泵基因AdeABC表达的相关性研究[J].中国抗生素杂志,2024,49(8):898-902. PAN B Z, LIU Y, SU J S, et al. Correlation between bio-film formation and e?ux pump gene AdeABC expression in carbapenem resistant Acinetobacter baumannii[J]. Chi-nese Journal of Antibiotics, 2024, 49(8): 898-902.
[18] 谈昀,刘萍,白永梅.2011～2015年鲍曼不动杆菌耐药相关基因及耐药性变迁研究[J].现代检验医学杂志,2017,32(1):53-56, 60. TAN Y, LIU P, BAI Y M. Study on the drug resistance related genes and drug resistance of Acinetobacter bau-mannii from 2011 to 2015[J]. Journal of Modern Labo-ratory Medicine, 2017, 32(1): 53-56, 60.
[19] 苏爱美,韦涌涛,王东平.耐碳青霉烯类鲍曼不动杆菌联合药敏试验研究[J].临床检验杂志,2024,42(4):267-271. SU A M, WEI Y T, WANG D P. Combination tests of drug sensitivity for carbapenem-resistant Acinetobacter baumannii[J]. Chinese Journal of Clinical Laboratory Science, 2024, 42(4): 267-271.
[20] 蔺飞,杜冰洁,高灿,等.鲍曼不动杆菌生物被膜对抗菌药物耐药性的影响[J].中国感染控制杂志,2018,17(1):1-5. LIN F, DU B J, GAO C, et al. Effect of Acinetobacter baumannii biofilm on antimicrobial resistance[J]. Chi-nese Journal of Infection Control, 2018, 17(1): 1-5.

相似文献/References:

[1]黄秋兰,钱巧慧,范德平,等.鱼腥草联合亚胺培南对碳青霉烯耐药铜绿假单胞菌杀菌效果的体外研究[J].现代检验医学杂志,2021,36(03):118.[doi:10.3969/j.issn.1671-7414.2021.03.027]
　HUANG Qiu-lan1a,QIAN Qiao-hui2,FAN De-ping1a,et al.Vitro Study on the Bactericidal Effect of Houttuynia Cordata Combined withImipenem Against Carbapenem Resistant Pseudomonas Aeruginosa[J].Journal of Modern Laboratory Medicine,2021,36(06):118.[doi:10.3969/j.issn.1671-7414.2021.03.027]
[2]唐金蓉,张 碟,李 盛.四种中药单体联合亚胺培南对耐碳青霉烯肺炎克雷伯菌体外抑菌作用研究[J].现代检验医学杂志,2022,37(06):162.[doi:10.3969/j.issn.1671-7414.2022.06.031]
　TANG Jin-rong,ZHANG Die,LI Sheng.Antibacterial Activity of Four Traditional Chinese Medicine Momonomers Combined with Imipenem Against Carbapenem-resistant Klebsiella Pneumoniae in Vitro[J].Journal of Modern Laboratory Medicine,2022,37(06):162.[doi:10.3969/j.issn.1671-7414.2022.06.031]

备注/Memo

备注/Memo:
基金项目：四川省医学科研课题计划（编号S23039）。
作者简介：欧阳龙（1988-），男，硕士，副主任技师，研究方向：临床检验诊断学，E-mail：835366169@qq.com。
通讯作者：肖亚雄（1981-），男，硕士，主任技师，研究方向：细菌耐药机制研究，E-mail：82609161@qq.com。concentration; biofilm
更新日期/Last Update: 2025-11-15