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The polymyxins (colistin and polymyxin B) are basic polypeptides that are bactericidal for certain gram-negative aerobic rods, including Pseudomonas. Because of poor distribution into tissues and substantial toxicity (primarily nephrotoxicity and neurotoxicity), systemic use of these agents has been limited to infections caused by multidrug-resistant gram-negative organisms that are sensitive only to the polymyxins. Colistin is used for pan-resistant Acinetobacter baumanii and P aeruginosa and CRE infections. However, safer alternatives are available; ceftolozane-tazobactam is clinically effective against multidrug-resistant P aeruginosa with fewer toxicities, and ceftazidime-avibactam is safer and more effective in the treatment of infection caused by CRE. Meropenem-vaborbactam is likely more effective and certainly less toxic than colistin. A number of issues limit the safe, effective use of the polymyxins, including confusion between polymyxin B and colistin, absence of pharmaceutical standards, uncertainties regarding susceptibility testing and breakpoints, pharmacokinetics in special patient populations, and the role of combination therapy. Baseline renal impairment and older age strongly predict acute kidney injury. Higher doses of colistin are associated with increased microbiologic success and decreased 7-day mortality; however, they are also associated with worsened kidney function. While not associated with confirmed improved clinical outcomes, some clinicians recommend capping the dose at 9 million units/daily of colistin methanesulfonate and adding a second medication such as a carbapenem.

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Pogue  JM  et al. Ceftolozane/tazobactam vs polymyxin or aminoglycoside-based regimens for the treatment of drug-resistant Pseudomonas aeruginosa. Clin Infect Dis. 2020;71:304.
[PubMed: 31545346]  
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Tsuji  BT  et al. International consensus guidelines for the optimal use of the polymyxins: endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39:10.
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Van Duin  D  et al. Colistin versus ceftazidime-avibactam in the treatment of infections due to carbapenem-resistant Enterobacteriaceae. Clin Infect Dis. 2018;66:163.
[PubMed: 29020404]  

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