Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review

被引:633
作者
Zavascki, Alexandre Prehn
Goldani, Luciano Zubaran
Li, Jian
Nation, Roger L.
机构
[1] Pontificia Univ Catolica Rio Grande do Sul, Hosp Sao Lucas, Infect Dis Serv, BR-90610000 Porto Alegre, RS, Brazil
[2] Univ Fed Rio Grande do Sul, Med Sci Postgrad Program, Porto Alegre, RS, Brazil
[3] Hosp Clin Porto Alegre, Div Infect Dis, Porto Alegre, RS, Brazil
[4] Monash Univ, Victorian Coll Pharm, Facil Antiinfect Drug Dev & Innovat, Parkville, Vic 3052, Australia
关键词
polymyxins; antimicrobial cationic peptides; multiple bacterial drug resistance; GRAM-NEGATIVE BACTERIA; IN-VITRO ACTIVITY; 2-COMPONENT REGULATORY SYSTEM; QUALITY-CONTROL GUIDELINES; INTENSIVE-CARE-UNIT; PSEUDOMONAS-AERUGINOSA; ACINETOBACTER-BAUMANNII; ANTIMICROBIAL PEPTIDES; COLISTIN METHANESULFONATE; LIPID-A;
D O I
10.1093/jac/dkm357
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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.
引用
收藏
页码:1206 / 1215
页数:10
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