title: Clinical translation of polymyxin-based combination therapy: Facts, challenges and future opportunities.
abstract: The emergence and spread of multidrug resistant Gram-negative bacteria has led to a resurgence in the clinical use of polymyxin antibiotics. However, the prevalence of polymyxin resistance is on the rise at an alarming rate, motivating the idea of combination therapy to sustain the revival of these "old" antibiotics. Although ample evidence in favor of combination therapy has emerged, it seems impracticable and confusing to find a promising combination from the diverse reports or gain adequate information on the efficacy and safety profile. With a stagnating discovery pipeline of novel antimicrobials, there is a clear need to fill the knowledge gaps in translating these basic research data to beneficial clinical practice. In this review, we examined the factors and ambiguities that stand as major hurdles in bringing polymyxin combination therapy to bedside care, highlighting the importance and urgency of incorporating translational research insights into areas of difficulty. We also discussed future research priorities that are essential to gather the necessary evidence and insights for promoting the best possible use of polymyxins in combination therapy.
authors.affiliation: Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China. Electronic address: gycsh@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Shao
authors.affiliation: State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: happyzxzx@126.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D003091:Colistin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011112:Polymyxin B / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011113:Polymyxins / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D057170:Translational Research, Biomedical
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins; D011112:Polymyxin B; D003091:Colistin
keywords: Clinical translation; Combination therapy; Multidrug resistance; Polymyxins