Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Colistin: An overview

INTRODUCTION

Colistin (also called polymyxin E) belongs to the polymyxin group of antibiotics [1]. It was first isolated in Japan in 1949 from Bacillus polymyxa var. colistinus, and became available for clinical use in 1959 [2,3]. Colistin was given as an intramuscular injection for the treatment of gram-negative infections but fell out of favor after aminoglycosides became available because of its significant side effects. It was later used as topical therapy as part of selective digestive tract decontamination and is still used in aerosolized form for patients with cystic fibrosis. (See "Cystic fibrosis: Antibiotic therapy for lung disease".)

More recently, a number of centers around the world have used colistin intravenously for otherwise panresistant nosocomial infections, especially those due to Pseudomonas and Acinetobacter spp [4-8].

The spectrum of activity, mechanisms of action and resistance, pharmacokinetics, interactions with other drugs, and adverse effects of colistin will be reviewed here. The clinical settings in which colistin may be used are discussed separately in the appropriate topic reviews.

MECHANISM OF ACTION

Colistin is a bactericidal drug that binds to lipopolysaccharides and phospholipids in the outer cell membrane of gram-negative bacteria. It competitively displaces divalent cations from the phosphate groups of membrane lipids, which leads to disruption of the outer cell membrane, leakage of intracellular contents, and bacterial death [3,9,10].

In addition to its bactericidal effect, colistin can bind and neutralize lipopolysaccharide (LPS) and prevent the pathophysiologic effects of endotoxin in the circulation [11,12].
To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2009 UpToDate, Inc.
References Top
  1. Falagas, ME, Kasiakou, SK. Colistin: The revival of polymyxins for the management of multidrug-resistant Gram-negative bacterial infections. Clin Infect Dis 2005; 40:1333.
  2. Kumazawa, J, Yagisawa, M. The history of antibiotics: the Japanese story. J Infect Chemother 2002; 8:125.
  3. Kucers, A, Crowe, S, Grayson, ML, Hoy, JF. The use of antibiotics. Heinemann, London. 5th Edition, 1997:899.
  4. Levin, AS, Barone, AA, Penco, J, et al. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter Baumanii. Clin Infect Dis 1999; 28:1008.
  5. Garnacho-Montero, J, Ortiz-Leyba, C, Jimenez-Jimenez, FJ, et al. Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: A comparison with imipenem-susceptible VAP. Clin Infect Dis 2003; 36:1111.
  6. Markou, N, Apostolakos, H, Koumoudiou, C, et al. Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients. Crit Care 2003; 7:R78.
  7. Linden, PK, Kusne, S, Coley, K, et al. Use of parenteral colistin for the treatment of serious infection due to antimicrobial-resistant Pseudomonas aeruginosa. Clin Infect Dis 2003; 37:e154.
  8. Michalopoulos, AS, Tsiodras, S, Rellos, K, et al. Colistin treatment in patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria: the renaissance of an old antibiotic. Clin Microbiol Infect 2005; 11:115.
  9. Evans, ME, Feola, DJ, Rapp, RP. Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant Gram-negative bacteria. Ann Pharmacother 1999; 33:960.
  10. Li, J, Turnidge, J, Milne, R, et al. In vitro pharmacodynamic properties of colistin and colistin methanesulfonate against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother 2001; 45:781.
  11. Giacometti, A, Cirioni, O, Ghiselli, R, et al. Antiendotoxin activity of antimicrobial peptides and glycopeptides. J Chemother 2003; 15:129.
  12. Warren, HS, Kania, SA, Siber, GR. Binding and neutralization of bacterial lipopolysaccharide by colistin nonapeptide. Antimicrob Agents Chemother 1985; 28:107.
  13. Groisman, EA, Kayser, J, Soncini, FC. Regulation of polymyxin resistance and adaptation to low-Mg2+ environments. J Bacteriol 1997; 179:7040.
  14. Young, ML, Bains, M, Bell, A, Hancock, RE. Role of Pseudomonas aeruginosa outer membrane protein OprH in polymyxin and gentamicin resistance: isolation of an OprH-deficient mutant by gene replacement techniques. Antimicrob Agents Chemother 1992; 36:2566.
  15. Li, J, Rayner, CR, Nation, RL, et al. Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2006; 50:2946.
  16. Owen, RJ, Li, J, Nation, RL, Spelman, D. In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates. J Antimicrob Chemother 2007; 59:473.
  17. Levin, AS. Treatment of Acinetobacter spp infections. Expert Opin Pharmacother 2003; 4:1289.
  18. Arroyo, LA, Garcia-Curiel, A, Pachon-Ibanez, ME, et al. Reliability of the E-test method for detection of colistin resistance in clinical isolates of Acinetobacter baumannii. J Clin Microbiol 2005; 43:903.
  19. Gales, AC, Reis, AO, Jones, RN. Contemporary assessment of antimicrobial susceptibility testing methods for polymyxin B and colistin: review of available interpretative criteria and quality control guidelines. J Clin Microbiol 2001; 39:183.
  20. Lo-Ten-Foe, JR, de Smet, AM, Diederen, BM, et al. Comparative evaluation of the VITEK2, disk diffusion, E-test, broth microdilution, and agar dilution susceptibility testing methods for colistin in clinical isolates (including heteroresistant E.cloacae and A. baumannii strains). Antimicrob Agents Chemother 2007; :.
  21. Tan, TY, Ng, LS, Poh, K. Susceptibility testing of unconventional antibiotics against multiresistant Acinetobacter spp. by agar dilution and Vitek 2. Diagn Microbiol Infect Dis 2007; 58:357.
  22. Tan, TY, Ng, SY. Comparison of Etest, Vitek and agar dilution for susceptibility testing of colistin. Clin Microbiol Infect 2007; 13:541.
  23. Li, J, Nation, RL, Milne, RW, et al. Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria. Int J Antimicrob Agents 2005; 25:11.
  24. Pitt, TL, Sparrow, M, Warner, M, Stefanidou, M. Survey of resistance of Pseudomonas aeruginosa from UK patients with cystic fibrosis to six commonly prescribed antimicrobial agents. Thorax 2003; 58:794.
  25. Schulin, T. In vitro activity of the aerosolized agents colistin and tobramycin and five intravenous agents against Pseudomonas aeruginosa isolated from cystic fibrosis patients in southwestern Germany. J Antimicrob Chemother 2002; 49:403.
  26. Karabinis, A, Paramythiotou, E, Mylona-Petropoulou, D, et al. Colistin for Klebsiella pneumoniae-associated sepsis. Clin Infect Dis 2004; 38:e7.
  27. Reed, MD, Stern, RC, O'Riordan, MA, Blumer, JL. The pharmacokinetics of colistin in patients with cystic fibrosis. J Clin Pharmacol 2001; 41:645.
  28. Li, J, Coulthard, K, Milne, R, et al. Steady-state pharmacokinetics of intravenous colistin methanesulphonate in patients with cystic fibrosis. J Antimicrob Chemother 2003; 52:987.
  29. Kunin, CM, Bugg, A. Binding of polymyxin antibiotics to tissues: the major determinant of distribution and persistence in the body. J Infect Dis 1971; 124:394.
  30. Stein, A, Raoult, D. Colistin: an antimicrobial for the 21st century?. Clin Infect Dis 2002; 35:901.
  31. Fernandez-Viladrich, P, Corbella, X, Corral, L, et al. Successful treatment of ventriculitis due to carbapenem-resistant Acinetobacter baumannii with intraventricular colistin sulfomethate sodium. Clin Infect Dis 1999; 28:916.
  32. Jimenez-Mejias, ME, Pichardo-Guerrero, C, Marquez-Rivas, FJ, et al. Cerebrospinal fluid penetration and pharmacokinetic/pharmacodynamic parameters of intravenously administered colistin in a case of multidrug-resistant Acinetobacter baumannii meningitis. Eur J Clin Microbiol Infect Dis 2002; 21:212.
  33. Vasen, W, Desmery, P, Ilutovich, S, Di Martino, A. Intrathecal use of colistin. J Clin Microbiol 2000; 38:3523.
  34. Benifla, M, Zucker, G, Cohen, A, Alkan, M. Successful treatment of Acinetobacter meningitis with intrathecal polymyxin E. J Antimicrob Chemother 2004; 54:290.
  35. Berlana, D, Llop, JM, Fort, E, et al. Use of colistin in the treatment of multiple-drug-resistant Gram-negative infections. Am J Health Syst Pharm 2005; 62:39.
  36. http://www.fda.gov/cder/drug/advisory/colistimethate.htm (Accessed on July 30, 2007).
  37. Kallel, H, Hergafi, L, Bahloul, M, et al. Safety and efficacy of colistin compared with imipenem in the treatmentof ventilator-associated pneumonia: a matched case-control study. Intensive Care Med 2007; 33:1162.
  38. Goverman, J, Weber, JM, Keaney, TJ, Sheridan, RL. Intravenous colistin for the treatment of multi-drug resistant, gram-negative infection in the pediatric burn population. J Burn Care Res 2007; 28:421.
  39. Linden, PK, Paterson, DL. Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clin Infect Dis 2006; 43 Suppl 2:S89.
  40. Koch-Weser, J, Sidel, VW, Federman, EB, et al. Adverse effects of sodium colistimethate. Manifestations and specific reaction rates during 317 courses of therapy. Ann Intern Med 1970; 72:857.
  41. Hartzell, JD, Neff, R, Ake, J, et al. Nephrotoxicity associated with intravenous colistin (colistimethate sodium) treatment at a tertiary care medical center. Clin Infect Dis 2009; 48:1724.
  42. Falagas, ME, Rizos, M, Bliziotis, IA, et al. Toxicity after prolonged (more than four weeks) administration of intravenous colistin. BMC Infect Dis 2005; 5:1.
  43. WOLINSKY, E, HINES, JD. Neurotoxic and nephrotoxic effects of clolistin in patients with renal disease. N Engl J Med 1962; 266:759.
  44. Lindesmith, LA, Baines, RD Jr, Bigelow, DB, Petty, TL. Reversible respiratory paralysis associated with polymyxin therapy. Ann Intern Med 1968; 68:318.
  45. Beringer, P. The clinical use of colistin in patients with cystic fibrosis. Curr Opin Pulm Med 2001; 7:434.
white circle LOG IN
white circle DEMO