Polymyxin combinations: pharmacokinetics and pharmacodynamics for rationale use.
Polymyxin combinations: pharmacokinetics and pharmacodynamics for rationale use.
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DOI：
10.1002/phar.1537
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发表时间：
2015-01
期刊：
影响因子：
4.1
通讯作者：
Tsuji, Brian T.
中科院分区：
文献类型：
--
作者：
Bergen, Phillip J.;Bulman, Zackery P.;Saju, Sarith;Bulitta, Juergen B.;Landersdorfer, Cornelia;Forrest, Alan;Li, Jian;Nation, Roger L.;Tsuji, Brian T.
自20世纪80年代重新进入临床以来，多粘菌素类抗生素粘杆菌素(作为一种非活性前体药物)和多粘菌素B(多粘菌素B)作为一种非活性前体药物静脉给药，在抢救原本无法治愈的革兰氏阴性感染方面发挥了重要作用。然而，新出现的CMS/粘菌素和多粘菌素B的药效学和药代动力学数据表明，多粘菌素单一疗法不太可能产生可靠有效的血浆浓度。此外，即使在药物浓度超过临床所达到的浓度时，单一疗法的再生和耐药性的出现也是常见的报道。鉴于这种情况，越来越多地在临床上使用的多粘菌素联合疗法已被建议作为一种可能的手段来增加抗菌活性和减少耐药性的发展。虽然相当多的体外数据支持这一观点，但多粘菌素联合治疗患者的研究最近才开始。目前可用的多粘菌素联合用药的临床数据通常仅限于回溯性分析和使用达到低血药浓度的传统给药方案的小型、低功率、前瞻性研究。考虑到多粘菌素耐药性迅速发展的潜力，迫切需要设计良好的临床试验，包括更高剂量的多粘菌素方案，以提供关于多粘菌素联合疗法与单一疗法相比的作用的更明确的答案。本文就CMS/粘菌素和多粘菌素B联合治疗的体外和临床研究进展作一综述。
Since their reintroduction into the clinic in the 1980s, the polymyxin antibiotics colistin—administered intravenously as an inactive prodrug, colistin methanesulfonate (CMS)—and polymyxin B have assumed an important role as salvage therapy for otherwise untreatable gram-negative infections. However, the emerging pharmacodynamic and pharmacokinetic data on CMS/colistin and polymyxin B indicate that polymyxin monotherapy is unlikely to generate plasma concentrations that are reliably efficacious. Additionally, regrowth and the emergence of resistance with monotherapy are commonly reported even when concentrations exceed those achieved clinically. Given this situation, polymyxin combination therapy, which is increasingly being used clinically, has been suggested as a possible means of increasing antimicrobial activity and reducing the development of resistance. Although considerable in vitro data support this view, investigations of polymyxin combination therapy in patients have only recently commenced. The currently available clinical data for polymyxin combinations are generally limited to retrospective analyses and small, low-powered, prospective studies using traditional dosage regimens that achieve low plasma concentrations. Considering the potential for rapid development of resistance to polymyxins, well-designed clinical trials that include higher-dose polymyxin regimens are urgently required to provide a more definitive answer regarding the role of polymyxin combination therapy compared with monotherapy. In this article, we provide an overview of key in vitro and clinical investigations examining CMS/colistin and polymyxin B combination therapy.
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DOI：
10.1007/s10096-006-0191-2
发表时间：
2006-09-01
影响因子：
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作者：
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