Zavascki Alexandre Prehn, Goldani Luciano Zubaran, Li Jian, Nation Roger L
Infectious Diseases Service, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
J Antimicrob Chemother. 2007 Dec;60(6):1206-15. doi: 10.1093/jac/dkm357. Epub 2007 Sep 17.
Polymyxins have re-emerged in clinical practice owing to the dry antibiotic development pipeline and worldwide increasing prevalence of nosocomial infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Polymyxin B and colistin (polymyxin E) have been ultimately considered as the last-resort treatment of such infections. Microbiological, pharmacokinetic, pharmacodynamic and clinical data available for polymyxin B are reviewed in this paper. Polymyxin B has rapid in vitro bactericidal activity against major MDR Gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. Acquired resistance to this agent is still rare among these pathogens. However, optimized dosage regimens are not known yet. Good clinical outcomes have been observed in the majority of the patients treated with intravenous polymyxin B in recent studies. However, these studies failed to provide definitive conclusions due to limitations of study design and additional clinical trials are required. Although combination therapy may be an attractive option based on some currently available in vitro data, clinical data supporting such recommendations are lacking. Since polymyxins will be increasingly used for the treatment of infections caused by MDR bacteria, clinical pharmacokinetic, pharmacodynamic and toxicodynamic studies underpinning the optimal use of these drugs are urgently required.
由于抗生素研发进展缓慢以及全球范围内耐多药（MDR）革兰氏阴性菌引起的医院感染患病率不断上升，多粘菌素已重新出现在临床实践中。多粘菌素B和黏菌素（多粘菌素E）最终被视为此类感染的最后一线治疗药物。本文综述了多粘菌素B的微生物学、药代动力学、药效学和临床数据。多粘菌素B对主要的耐多药革兰氏阴性菌，如铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯菌具有快速的体外杀菌活性。在这些病原体中，对该药物获得性耐药仍然罕见。然而，尚未确定优化的给药方案。在最近的研究中，大多数接受静脉注射多粘菌素B治疗的患者都观察到了良好的临床结果。然而，由于研究设计的局限性，这些研究未能提供明确的结论，因此需要进行更多的临床试验。尽管基于目前一些体外数据，联合治疗可能是一个有吸引力的选择，但缺乏支持此类建议的临床数据。由于多粘菌素将越来越多地用于治疗由耐多药细菌引起的感染，因此迫切需要开展临床药代动力学、药效学和毒效学研究，以支持这些药物的最佳使用。
