Polymyxin B sulfate and colistin: Old antibiotics for emerging multiresistant gram-negative bacteria

BACKGROUND: Polymyxin B sulfate and colistin, also known as colistimethate, have not been used for many years because less toxic antimicrobials are available. Gram-negative bacteria that are resistant to the aminoglycosides, β-lactams, and fluoroquinolones are becoming more common. These bacteria are often susceptible to the polymyxins. OBJECTIVE: To present a review of the chemistry, antibacterial spectrum, dosing, pharmacokinetics, toxicity, and indications for polymyxin B sulfate and colistin. DATA SOURCE: A MEDLINE search (1966-1998) of the English-language literature was performed to identify primary literature on the polymyxins. Older citations (1949-1965) were identified through the bibliographies of these articles. STUDY SELECTION: All available reports of in vitro antibacterial activity, animal and clinical trials, and case reports were reviewed. DATA SYNTHESIS: The polymyxins are amphipathic molecules that interact with lipopolysaccharide in the bacterial outer membrane. They have potent antiendotoxic properties and antibacterial activity against Pseudomonas aeruginosa and many of the Enterobacteriaceae. Polymyxin B and colistin are usually given at a dose of 1.5-2.5 and 5 mg/kg/d, respectively, in two divided doses. Dosing must be altered in renal failure since the kidney is the primary route of elimination. Distribution into pleural fluid, joints, and cerebrospinal fluid is poor. Toxic effects involve the kidney and central nervous system. The polymyxins are recommended for serious systemic infections caused by gram-negative bacteria that are resistant to other agents. CONCLUSIONS: Polymyxin B sulfate and colistin have a role in the therapy of multidrug-resistant gram-negative bacterial infections.