Background: Successful treatment of Acinetobacter (A.) baumannii-associated infection is complicated by the emergence of multidrug resistance (MDR), particularly in clinical settings. This urges searching for new alternatives to encounter such health problem.
Aim: This study aimed to evaluate certain antibiotic combinations and CNPs either alone or in combination of some selected antibiotics for the purpose of combating MDR A. baumannii clinical isolates.
Methods: A total of 51 A. baumannii clinical isolates were recovered from discharged clinical specimens of the Clinical Microbiology Central Laboratory of AL Kasr Al Aini hospital, Cairo, Egypt. Conventional standard Lab tests were used for identification followed by recA gene testing for confirmation. Antimicrobial susceptibility tests were conducted out according to CLSI guidelines. Genotypic analysis using Enterobacterial Repetitive Intergenic Consensus-polymerase chain reaction (ERIC-PCR) of the respective isolates showed that they were clustered in nine clones. The prepared CNPs were characterized by dynamic light scattering and HR-transmission electron microscope imaging. Antibiotic combinations and co-effect of CNPs with some selected antibiotics (either each alone or in combination of two) were evaluated using the Checkerboard microdilution and minimum inhibitor concentration decrease factor (MDF) methods, respectively.
Results: The recovered 51 A. baumannii clinical isolates were MDR (100%) of these 92% (47/51) were extensively drug resistance (XDR). Combinations of colistin (CT)+meropenem (MEM) and MEM+tigecycline (TGC) showed synergism in 77.7% and 44.4% and additive effects in 22.3% and 55.6% of the tested MDR A. baumannii isolates (n=51), respectively. However, CT+TGC combination showed antagonism. CNPs exhibited good inhibitory activity (inhibition zones ranged from 24 to 31 mm) against selected nine MDR A. baumannii isolates (one isolate from each clone). The MIC of CNPs at concentrations (ranging from 1 to 5 mg/mL) were from 0.16 to 0.25 mg/mL, indicating good in vitro antimicrobial activities. CNPs (5 mg/mL) when combined with CT, TGC or MEM, CT+MEM and TGC+MEM significantly increased the susceptibilities of the MDR A. baumannii isolates to these antibiotics by 88.8%, 66.6%, 100%, 77.7%, and 44.4%, respectively. No significant effects were observed when CNPs (5 mg/mL) were combined with CT+TGC.
Conclusion: The current study demonstrated the significant in-vitro activities of CNPs either alone or in combination with CT, TGC or MEM, CT+MEM and TGC+MEM and the successful combinations of MEM either with CT or with TGC against the MDR A. baumannii pathogens. However, further in vivo studies should be conducted to verify such activities and their potential use in human.



中文翻译：

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抗生素组合和壳聚糖纳米颗粒对抗多药耐药鲍曼不动杆菌

背景：多药耐药性 (MDR) 的出现使鲍曼不动杆菌 (A.)相关感染的成功治疗变得复杂，尤其是在临床环境中。这促使人们寻找新的替代品来解决这种健康问题。
目的：本研究旨在评估某些抗生素组合和 CNP，无论是单独还是与某些选定的抗生素组合，以对抗 MDR A. baumannii临床分离株。
方法：共 51 个鲍曼不动杆菌临床分离物是从埃及开罗 AL Kasr Al Aini 医院临床微生物学中心实验室出院的临床标本中回收的。常规标准实验室测试用于识别，然后是rec用于确认的基因测试。根据 CLSI 指南进行抗菌药敏试验。使用肠杆菌重复基因间共有聚合酶链反应 (ERIC-PCR) 对各个分离株进行基因型分析，结果表明它们聚集在九个克隆中。通过动态光散射和 HR 透射电子显微镜成像对制备的 CNPs 进行了表征。分别使用棋盘微稀释法和最小抑制剂浓度降低因子 (MDF) 方法评估了 CNP 与某些选定抗生素（单独或两种组合）的抗生素组合和协同效应。
结果：回收的 51株鲍曼不动杆菌临床分离株为 MDR (100%)，其中 92% (47/51) 为广泛耐药 (XDR)。多粘菌素 (CT) + 美罗培南 (MEM) 和 MEM + 替加环素 (TGC) 的组合分别显示 77.7% 和 44.4% 的协同作用和 22.3% 和 55.6% 的测试耐多药鲍曼不动杆菌分离株 (n=51) 的叠加效应，分别. 然而，CT+TGC组合表现出拮抗作用。CNPs 对选定的 9 个 MDR A. baumannii分离株（每个克隆一个分离株）表现出良好的抑制活性（抑制区范围为 24 至 31 mm）。CNPs 在浓度（范围从 1 到 5 mg/mL）的 MIC 为 0.16 到 0.25 mg/mL，表明良好的体外抗菌活性。CNPs (5 mg/mL) 与 CT、TGC 或 MEM、CT+MEM 和 TGC+MEM 结合时显着增加了 MDR 的敏感性鲍曼不动杆菌对这些抗生素的分离率分别为 88.8%、66.6%、100%、77.7% 和 44.4%。当 CNP (5 mg/mL) 与 CT+TGC 结合时，未观察到显着影响。
结论：目前的研究证明了 CNP 单独或与 CT、TGC 或 MEM、CT+MEM 和 TGC+MEM 组合的显着体外活性，以及​​ MEM 与 CT 或与 TGC 的成功组合对抗 MDR A。鲍曼尼病原体。然而，应进行进一步的体内研究以验证这些活性及其在人类中的潜在用途。