Department of Biological Sciences, Faculty of Science, University of Calgary, Calgary, Alberta, Canada.
C-Crest Laboratories Inc., Montreal, Quebec, Canada.
J Antimicrob Chemother. 2022 May 29;77(6):1635-1644. doi: 10.1093/jac/dkac094.
Antibiotic resistance, biofilm and persistent infection of Pseudomonas aeruginosa is a perilous challenge in the healthcare system. Hence, a vast number of novel antipseudomonas approaches are currently being pursued. Our group focuses on exploring the efficacy of metal(loid)-based antimicrobials (MBAs) towards novel infection control solutions.
Initially, nine MBAs were tested for biofilm prevention and eradication efficacy. Synergistic potentials were then screened systematically in a total of 1920 combinatorial MBA concentrations, in laboratory media [CAMHB and LB] and infection-related simulated wound fluid (SWF). The antibiofilm efficacy of the silver nitrate (AgNO3; 'Ag') with potassium tellurite (K2TeO3; 'Te') combination was examined against clinical antibiotic-resistant isolates and compared with the most used antibiotics. The in vitro resistance acquisition test, for exploring the chance of getting future resistance, and meta-analysis, for estimating Ag/Te human cell cytotoxicity, were carried out.
The Ag/Te combination was identified as the most effective agent against P. aeruginosa biofilm. The application of the Ag/Te combination was quite effective against all clinical isolates. Comparison of clinical isolates with indicator strains showed clinical isolates are gaining resistance against the antibiotics (especially gentamicin) and Ag, while they are susceptible to Te and particularly the Ag/Te combination. The chance of getting future resistance against Ag/Te as a mixture was remarkably lower than the individual application of each metal. Te has significantly lower human cell cytotoxicity in comparison with Ag.
Te could be an appropriate alternative against P. aeruginosa biofilms (existing or prevention thereof), especially in combination with Ag.
铜绿假单胞菌的抗生素耐药性、生物膜和持续性感染是医疗保健系统面临的一个严重挑战。因此，目前正在探索大量新的抗铜绿假单胞菌方法。我们的研究小组专注于探索金属（类）抗菌剂（MBAs）在新型感染控制解决方案方面的效果。
最初，测试了 9 种 MBA 对生物膜预防和消除的功效。然后，在实验室培养基[CAMHB 和 LB]和感染相关模拟伤口液（SWF）中，系统筛选了总共 1920 种 MBA 组合浓度的协同潜力。硝酸银（AgNO3；“Ag”）与碲酸钾（K2TeO3；“Te”）组合的抗生物膜功效针对临床抗生素耐药分离株进行了检查，并与最常用的抗生素进行了比较。进行了体外耐药获得试验，以探索未来获得耐药的机会，以及荟萃分析，以评估 Ag/Te 对人类细胞的细胞毒性。
Ag/Te 组合被鉴定为抗铜绿假单胞菌生物膜最有效的试剂。Ag/Te 组合在所有临床分离株中的应用都非常有效。与指示株相比，临床分离株对抗生素（特别是庆大霉素）和 Ag 的耐药性增加，而对 Te 特别是 Ag/Te 组合的耐药性较低。作为混合物，获得对 Ag/Te 的未来耐药性的机会明显低于单独使用每种金属的机会。与 Ag 相比，Te 对人类细胞的细胞毒性明显较低。
Te 可能是对抗铜绿假单胞菌生物膜（现有或预防）的一种合适替代品，特别是与 Ag 联合使用时。
