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生物源银纳米颗粒与美罗培南联合对耐碳青霉烯鲍曼不动杆菌的协同及成瘾性活性。

The synergic and addictive activity of biogenic silver nanoparticle associated with meropenem against carbapenem-resistant Acinetobacter baumannii.

作者信息

Allend Suzane Olachea, Oliveira Garcia Marcelle, da Cunha Kamila Furtado, de Albernaz Déborah Trota Farias, Panagio Luciano Aparecido, Nakazaro Gerson, Reis Guilherme Fonseca, Oliveira Thaís Larré, Neto Amilton Clair Pinto Seixas, Hartwig Daiane Drawanz

机构信息

Department of Microbiology and Parasitology, Institute of Biology, Federal University of Pelotas, CEP 96010-900 Pelotas, RS, Brazil.

Department of Microbiology, State University of Londrina, CEP 86057-970 Londrina, PR, Brazil.

出版信息

J Appl Microbiol. 2024 Mar 1;135(3). doi: 10.1093/jambio/lxae046.

Abstract

AIMS

Antibiotic management of infections caused by Acinetobacter baumannii often fails due to antibiotic resistance (especially to carbapenems) and biofilm-forming strains. Thus, the objective here was to evaluate in vitro the antibacterial and antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) combined with meropenem, against multidrug-resistant isolates of A. baumannii.

METHODS AND RESULTS

In this study, A. baumannii ATCC® 19606™ and four carbapenem-resistant A. baumannii (Ab) strains were used. The antibacterial activity of Bio-AgNP and meropenem was evaluated through broth microdilution. The effect of the Bio-AgNP association with meropenem was determined by the checkboard method. Also, the time-kill assay and the integrity of the bacterial cell membrane were evaluated. Furthermore, the antibiofilm activity of Bio-AgNP and meropenem alone and in combination was determined. Bio-AgNP has antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration ranging from 0.46 to 1.87 μg ml-1. The combination of Bio-AgNP and meropenem showed a synergistic and additive effect against Ab strains, and Bio-AgNP was able to reduce the MIC of meropenem from 4- to 8-fold. Considering the time-kill of the cell, meropenem and Bio-AgNP when used in combination reduced bacterial load to undetectable levels within 10 min to 24 h after treatment. Protein leakage was observed in all treatments evaluated. When combined, meropenem/Bio-AgNP presents biofilm inhibition for Ab2 isolate and ATCC® 19606™, with 21% and 19%, and disrupts the biofilm from 22% to 50%, respectively. The increase in nonviable cells in the biofilm can be observed after treatment with Bio-AgNP and meropenem in carbapenem-resistant A. baumannii strains.

CONCLUSIONS

The combination of Bio-AgNP with meropenem can be a therapeutic option in the treatment of infections caused by carbapenem-resistant A. baumannii.

摘要

目的

由于鲍曼不动杆菌对抗生素耐药(尤其是对碳青霉烯类抗生素耐药)以及形成生物膜的菌株,由其引起的感染的抗生素治疗常常失败。因此,本研究的目的是在体外评估生物源银纳米颗粒(Bio-AgNP)联合美罗培南对多重耐药鲍曼不动杆菌分离株的抗菌和抗生物膜活性。

方法与结果

在本研究中,使用了鲍曼不动杆菌ATCC® 19606™和四株耐碳青霉烯类鲍曼不动杆菌(Ab)菌株。通过肉汤微量稀释法评估Bio-AgNP和美罗培南的抗菌活性。采用棋盘法确定Bio-AgNP与美罗培南联合使用的效果。此外,还评估了时间杀菌试验和细菌细胞膜的完整性。此外,还测定了Bio-AgNP和美罗培南单独及联合使用时的抗生物膜活性。Bio-AgNP具有抗菌活性,其最低抑菌浓度(MIC)和最低杀菌浓度范围为0.46至1.87μg/ml-1。Bio-AgNP与美罗培南的联合使用对Ab菌株显示出协同和相加作用,并且Bio-AgNP能够将美罗培南的MIC降低4至8倍。考虑到细胞的时间杀菌情况,美罗培南和Bio-AgNP联合使用在治疗后10分钟至24小时内将细菌载量降低到检测不到的水平。在所有评估的处理中均观察到蛋白质泄漏。联合使用时,美罗培南/Bio-AgNP对Ab2分离株和ATCC® 19606™具有生物膜抑制作用,抑制率分别为21%和19%,并分别使生物膜破坏22%至50%。在用Bio-AgNP和美罗培南处理耐碳青霉烯类鲍曼不动杆菌菌株后,可以观察到生物膜中无活力细胞的增加。

结论

Bio-AgNP与美罗培南联合使用可作为治疗耐碳青霉烯类鲍曼不动杆菌引起的感染的一种治疗选择。

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