JAC Advance Access originally published online on September 17, 2007
Journal of Antimicrobial Chemotherapy 2007 60(6):1206-1215; doi:10.1093/jac/dkm357
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Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review
1 Infectious Diseases Service, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil 2 Medical Sciences Postgraduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil 3 Division of Infectious Diseases, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil 4 Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia
* Correspondence address. Serviço de Infectologia, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, 6690 Ipiranga Avenue, 90610-000 Porto Alegre, RS, Brazil. Tel/Fax: +55-51-33621850; E-mail: apzavascki{at}terra.com.br
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.
Keywords: polymyxins , antimicrobial cationic peptides , multiple bacterial drug resistance
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