Tran Thien B, Cheah Soon-Ee, Yu Heidi H, Bergen Phillip J, Nation Roger L, Creek Darren J, Purcell Anthony, Forrest Alan, Doi Yohei, Song Jiangning, Velkov Tony, Li Jian
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
Centre for Medicine Use and Safety, Monash University, Melbourne, Australia.
J Antibiot (Tokyo). 2016 Jun;69(6):415-21. doi: 10.1038/ja.2015.127. Epub 2015 Dec 16.
Polymyxins, an old class of antibiotics, are currently used as the last resort for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii. However, recent pharmacokinetic and pharmacodynamic data indicate that monotherapy can lead to the development of resistance. Novel approaches are urgently needed to preserve and improve the efficacy of this last-line class of antibiotics. This study examined the antimicrobial activity of novel combination of polymyxin B with anthelmintic closantel against A. baumannii. Closantel monotherapy (16 mg l(-1)) was ineffective against most tested A. baumannii isolates. However, closantel at 4-16 mg l(-1) with a clinically achievable concentration of polymyxin B (2 mg l(-1)) successfully inhibited the development of polymyxin resistance in polymyxin-susceptible isolates, and provided synergistic killing against polymyxin-resistant isolates (MIC ⩾4 mg l(-1)). Our findings suggest that the combination of polymyxin B with closantel could be potentially useful for the treatment of MDR, including polymyxin-resistant, A. baumannii infections. The repositioning of non-antibiotic drugs to treat bacterial infections may significantly expedite discovery of new treatment options for bacterial 'superbugs'.
多黏菌素是一类古老的抗生素，目前被用作治疗多重耐药鲍曼不动杆菌的最后手段。然而，最近的药代动力学和药效学数据表明，单一疗法可能会导致耐药性的产生。迫切需要新的方法来维持和提高这类一线抗生素的疗效。本研究检测了多黏菌素B与驱虫药氯氰碘柳胺钠联合使用对鲍曼不动杆菌的抗菌活性。氯氰碘柳胺钠单一疗法（16 mg l(-1)）对大多数测试的鲍曼不动杆菌分离株无效。然而，4至16 mg l(-1)的氯氰碘柳胺钠与临床可达到的多黏菌素B浓度（2 mg l(-1)）联合使用，成功抑制了对多黏菌素敏感的分离株中多黏菌素耐药性的产生，并对多黏菌素耐药分离株（MIC⩾4 mg l(-1)）具有协同杀伤作用。我们的研究结果表明，多黏菌素B与氯氰碘柳胺钠联合使用可能对治疗包括耐多黏菌素鲍曼不动杆菌感染在内的多重耐药菌感染有潜在作用。将非抗生素药物重新定位用于治疗细菌感染可能会显著加快发现针对细菌“超级病菌”的新治疗方案。
