School of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.
J Med Microbiol. 2021 Mar;70(3). doi: 10.1099/jmm.0.001304. Epub 2021 Jan 15.
There is an urgent need for effective therapies against bacterial infections, especially those caused by antibiotic-resistant Gram-negative pathogens. Synergistic combinations of existing antimicrobials show promise due to their enhanced efficacies and reduced dosages which can mitigate adverse effects, and therefore can be used as potential antibacterial therapy. In this study, we sought to characterize the interaction of 5-nitrofurans, vancomycin and sodium deoxycholate (NVD) against pathogenic bacteria. The synergy of the NVD combination was investigated in terms of growth inhibition and bacterial killing using checkerboard and time-kill assays, respectively. Using a three-dimensional checkerboard assay, we showed that 5-nitrofurans, sodium deoxycholate and vancomycin interact synergistically in the growth inhibition of 15 out of 20 Gram-negative strains tested, including clinically significant pathogens such as carbapenemase-producing , and , and interact indifferently against the Gram-positive strains tested. The time-kill assay further confirmed that the triple combination was bactericidal in a synergistic manner. This study demonstrates the synergistic effect of 5-nitrofurans, sodium deoxycholate and vancomycin against Gram-negative pathogens and highlights the potential of the combination as a treatment for Gram-negative and Gram-positive infections.
针对细菌感染,特别是由抗生素耐药革兰氏阴性病原体引起的感染,我们迫切需要有效的治疗方法。由于增效作用和减少剂量,现有的抗菌药物联合使用显示出了希望,因为这些方法可以减轻不良反应,因此可以用作潜在的抗菌治疗方法。在这项研究中,我们试图研究 5-硝基呋喃类药物、万古霉素和去氧胆酸钠(NVD)与病原菌相互作用的特性。通过棋盘微量稀释法和时间杀伤试验分别评估了生长抑制和杀菌作用中 NVD 联合的协同作用。通过三维棋盘微量稀释法,我们发现 5-硝基呋喃类药物、去氧胆酸钠和万古霉素在 20 株革兰氏阴性菌中有 15 株的生长抑制中表现出协同作用,包括临床重要的病原体如产生碳青霉烯酶的 和 ,并且对测试的革兰氏阳性菌表现出中性相互作用。时间杀伤试验进一步证实,三联组合以协同方式具有杀菌作用。这项研究表明 5-硝基呋喃类药物、去氧胆酸钠和万古霉素对革兰氏阴性病原体具有协同作用,并强调了该组合作为治疗革兰氏阴性和革兰氏阳性感染的潜力。