Gaurav Amit, Kothari Ashish, Omar Balram Ji, Pathania Ranjana
Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India.
Department of Microbiology, All India Institute of Medical Sciences Rishikesh, Rishikesh, Uttarakhand, India.
Int J Antimicrob Agents. 2020 Jul;56(1):106022. doi: 10.1016/j.ijantimicag.2020.106022. Epub 2020 May 19.
The increasing prevalence of antibiotic resistance in Pseudomonas aeruginosa has created an urgent need for suitable therapy. This study explored the pairing of doxycycline with other antipseudomonal antibiotics, and found that polymyxin B in combination with doxycycline had a synergistic effect against clinical strains of P. aeruginosa. This synergistic combination was studied by checkerboard assays and time-kill curve analysis. Further, in-vitro biofilm disruption, pyoverdine inhibition assays were performed. The efficacy of polymyxin B-doxycycline in combination, administered by inhalation, was evaluated using a mouse model of acute pneumonia. The combination was found to have a synergistic effect in both in-vitro and in-vivo studies. The combination decreased biofilms of P. aeruginosa and reduced the level of pyoverdine, an important siderophore of P. aeruginosa. In addition, the combination decreased the P. aeruginosa population by 3 log (P<0.01) in the mouse model of acute pneumonia, and showed an improvement in lung function by inhalation. To the best of the authors' knowledge, this is the first in-vivo study to evaluate the efficacy of polymyxin B in combination with doxycycline against P. aeruginosa, showing a possible promising option for acute pneumonia due to multi-drug-resistant P. aeruginosa.
铜绿假单胞菌抗生素耐药性的日益普遍，使得迫切需要合适的治疗方法。本研究探索了多西环素与其他抗铜绿假单胞菌抗生素的联合使用，发现多粘菌素B与多西环素联合使用对铜绿假单胞菌临床菌株具有协同作用。通过棋盘法和时间杀菌曲线分析对这种协同组合进行了研究。此外，还进行了体外生物膜破坏、绿脓菌素抑制试验。使用急性肺炎小鼠模型评估了吸入给药的多粘菌素B-多西环素联合用药的疗效。在体外和体内研究中均发现该联合用药具有协同作用。该联合用药可减少铜绿假单胞菌的生物膜，并降低绿脓菌素的水平，绿脓菌素是铜绿假单胞菌的一种重要铁载体。此外，在急性肺炎小鼠模型中，该联合用药使铜绿假单胞菌数量减少了3个对数（P<0.01），并通过吸入显示肺功能有所改善。据作者所知，这是第一项评估多粘菌素B与多西环素联合使用对铜绿假单胞菌疗效的体内研究，显示出对多重耐药铜绿假单胞菌所致急性肺炎可能是一个有前景的选择。
