Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, 48201, USA.
Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, 48201, USA.
Infect Dis Ther. 2014 Dec;3(2):69-81. doi: 10.1007/s40121-014-0051-9. Epub 2014 Dec 5.
As antibiotic resistance continues to increase among Gram-negative organisms such as Acinetobacter baumannii there is a growing need for novel therapies to overcome these resistance mechanisms. Antibiotics active against multidrug-resistant A. baumannii (MDRAB) are few, and agents in development are primarily active against other multidrug-resistant Gram-negative organisms. The combinations of colistin and antimicrobials such as glycopeptides and lipopeptides are unique potential treatment modalities against MDRAB. For both lipopeptides and glycopeptides in vitro data have demonstrated significant synergy, resulting in rapid bactericidal activity in time-kill curves. Several invertebrate in vivo models have also demonstrated increased survival compared to colistin alone. Currently, very little clinical data have focused on using these combinations for infections caused exclusively by multidrug-resistant Gram-negatives. The combination of vancomycin and colistin has been studied with conflicting results regarding both improved outcomes and risk of nephrotoxicity. Although in vitro and in vivo models have proved promising, further investigation is required to provide clinical data necessary to support the use of these combinations. The objective of this review is to summarize literature currently available for the novel combination of lipopeptides or glycopeptides with colistin for the treatment of A. baumannii, in particular MDRAB.
随着革兰氏阴性菌(如鲍曼不动杆菌)对抗生素的耐药性不断增加,人们越来越需要新型疗法来克服这些耐药机制。针对多药耐药鲍曼不动杆菌(MDRAB)的抗生素很少,正在开发的药物主要针对其他多药耐药革兰氏阴性菌。多粘菌素与糖肽和脂肽等抗菌药物联合使用是针对 MDRAB 的独特潜在治疗方式。体外数据表明,脂肽和糖肽均具有显著协同作用,在时间杀伤曲线中迅速产生杀菌活性。几项无脊椎动物体内模型也表明,与单独使用多粘菌素相比,存活率有所提高。目前,很少有临床数据专门针对这些组合用于仅由多药耐药革兰氏阴性菌引起的感染。万古霉素和多粘菌素联合使用的研究结果存在争议,既包括改善结果,也包括肾毒性风险。尽管体外和体内模型都很有前景,但仍需要进一步研究以提供必要的临床数据来支持这些组合的使用。本综述的目的是总结目前可用于治疗鲍曼不动杆菌,特别是多药耐药鲍曼不动杆菌的脂肽或糖肽与多粘菌素联合使用的相关文献。