title: The safety of polymyxin antibiotics.
abstract: BACKGROUND
  The emergence of multidrug-resistant gram-negative bacteria has led to the increasing use of polymyxins. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic polymyxin therapy. Scientific evidence regarding safety associated with polymyxins remains limited.
  
  
  METHODS
  Case reports/case series, observational studies and clinical trials assessing safety and toxicity of polymyxins were critically reviewed.
  
  
  CONCLUSIONS
  Polymyxins are drugs with a narrow therapeutic range. Nephrotoxicity is associated with both host factors and polymyxin exposure, and recent studies suggest that the relative risk of nephrotoxicity is similar for colistin and polymyxin B. Studies that have examined the safety of polymyxins have several limitations. Considering the available evidence, toxicities that may develop while on polymyxin therapy most often are mild to moderate in magnitude and reversible in nature. Strategies to minimize toxicity associated with polymyxins have evolved and include avoidance of toxic medications, careful dosing, use of critical care, therapeutic drug monitoring and development of polymyxin derivatives. However, given that polymyxin use has re-emerged in an era of increased antimicrobial resistance, the presence of other treatment modalities may be limited. Therefore, clinicians must consider overall risk to benefit ratio of continuing versus stopping polymyxin treatment and optimize minimization strategies to reduce polymyxin-induced toxicities.
authors.affiliation: a 1 University of California, David Geffen School of Medicine, Division of Infectious Diseases, Department of Medicine , Los Angeles, CA 90095, USA.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kelesidis
authors.affiliation: b 2 Alfa Institute of Biomedical Sciences (AIBS) , 9 Neapoleos Street, 151 23 Marousi, Athens, Greece +30 69 46 11 00 00 ; +30 21 06 83 96 05 ; m.falagas@aibs.gr.|c 3 Tufts University School of Medicine, Department of Medicine , Boston, MA, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Falagas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016903:Drug Monitoring / Q000379:methods; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D020258:Neurotoxicity Syndromes / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D011113:Polymyxins / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins
keywords: antimicrobial resistance; colistin; nephrotoxicity; neurotoxicity; polymyxin B; polymyxins; safety; toxicity