Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Department of Medical Microbiology, College of Health Science, Hawler Medical University, Erbil, Iraq.
Sci Rep. 2022 Sep 9;12(1):15254. doi: 10.1038/s41598-022-19698-0.
Nanotechnology is being investigated for its potential to improve nanomedicine for human health. The purpose of this study was to isolate carbapenemase-producing Gram-negative bacilli (CPGB), investigate the presence of carbapenemase resistance genes, determine their antibiogram and ability to biosynthesise silver nanoparticles (Ag NPs), and estimate the antibacterial activity of Acinetobacter baumannii-biosynthesised Ag NPs on CPGB alone and in combination with antibiotics. A total of 51 CPGBs were isolated from various specimens in the study. The automated Vitek-2 system was used to identify and test these strains' antimicrobial susceptibilities. The carbapenemase resistance genes were identified using a polymerase chain reaction (PCR). Under the CPGB, A. baumannii could biosynthesise Ag NPs. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and field emission scanning electron were used to characterise Ag NPs. The antibacterial activity of Ag NP alone and in combination with antibiotics against CPGB was determined using the broth microdilution method, and their synergistic effect was determined using the checkerboard assay. bla and bla were the most commonly reported, and 90% of the isolates produced multiple carbapenemase genes. Tigecycline proved to be the most effective anti-CPGB antibiotic. Isolates with more resistance genes were more resistant to antibiotics, and isolates with three genes (42%) had the most extensively drug-resistant patterns (38%). A significant relationship was discovered between genetic and antibiotic resistance patterns. Only A. baumannii produced Ag NPs out of all the isolates tested. Ag NPs with a size of 10 nm were confirmed by UV-visible spectroscopy, FT-IR, XRD, and TEM analysis. The Ag NPs were effective against CPGB, with minimum inhibitory concentrations ranging from 64 to 8 μg/ml on average. Surprisingly, the combination of Ag NPs and antibiotics demonstrated synergistic and partial synergistic activity (fractional inhibitory concentration between 0.13 and 0.56) against CPGB, as well as a significant reduction in antibiotic concentrations, particularly in the case of A. baumanii versus ceftriaxone (1024 to 4 μg/ml). The notable synergistic activity of Ag NPs with antibiotics represents a valuable nanomedicine that may find clinical application in the future as a combined remedy.
纳米技术因其在改善人类健康的纳米医学方面的潜力而受到研究。本研究的目的是分离产碳青霉烯酶的革兰氏阴性杆菌（CPGB），研究碳青霉烯酶耐药基因的存在情况，确定其抗生素谱和生物合成银纳米颗粒（Ag NPs）的能力，并评估鲍曼不动杆菌生物合成的 Ag NPs 对 CPGB 的单独和联合抗生素的抗菌活性。从研究中的各种标本中分离出 51 株 CPGB。使用自动 Vitek-2 系统鉴定和测试这些菌株的抗菌药敏性。使用聚合酶链反应（PCR）鉴定碳青霉烯酶耐药基因。在 CPGB 下，鲍曼不动杆菌可以生物合成 Ag NPs。使用 X 射线衍射（XRD）、傅里叶变换红外光谱（FT-IR）、透射电子显微镜（TEM）和场发射扫描电子显微镜对 Ag NPs 进行了表征。使用肉汤微量稀释法测定 Ag NP 单独和联合抗生素对 CPGB 的抗菌活性，并通过棋盘试验测定其协同作用。bla 和 bla 是最常见的报道，90%的分离株产生多种碳青霉烯酶基因。替加环素被证明是最有效的抗 CPGB 抗生素。具有更多耐药基因的分离株对抗生素的耐药性更强，具有三种基因（42%）的分离株具有最广泛的耐药模式（38%）。发现遗传和抗生素耐药模式之间存在显著关系。在所测试的所有分离株中，只有鲍曼不动杆菌产生了 Ag NPs。通过紫外-可见光谱、FT-IR、XRD 和 TEM 分析证实 Ag NPs 的尺寸为 10nm。Ag NPs 对 CPGB 有效，平均最低抑菌浓度范围为 64 至 8μg/ml。令人惊讶的是，Ag NPs 与抗生素联合具有协同和部分协同作用（0.13 至 0.56 之间的抑菌浓度分数），并显著降低了抗生素浓度，特别是对于鲍曼不动杆菌与头孢曲松（1024 至 4μg/ml）。Ag NPs 与抗生素的显著协同活性代表了一种有价值的纳米医学，未来可能作为联合疗法在临床上得到应用。
