Colistin: An overview
- Graeme MacLaren, MBBS, FCICM, FRACP, FCCP, FCCM
Graeme MacLaren, MBBS, FCICM, FRACP, FCCP, FCCM
- National University Hospital, Singapore
- The Royal Children's Hospital, Melbourne, Australia
- Denis Spelman, MBBS, FRACP, FRCPA, MPH
Denis Spelman, MBBS, FRACP, FRCPA, MPH
- Adjunct Professor, Monash University
- Alfred Hospital, Victoria, Australia
Colistin (also called polymyxin E) belongs to the polymyxin group of antibiotics . 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 chronic pulmonary infection".)
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, 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].
- 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.
- Kumazawa J, Yagisawa M. The history of antibiotics: the Japanese story. J Infect Chemother 2002; 8:125.
- Kucers A, Crowe S, Grayson ML, Hoy JF. The use of antibiotics, 5th, Heinemann, London 1997. p.899.
- Levin AS, Barone AA, Penço J, et al. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin Infect Dis 1999; 28:1008.
- Garnacho-Montero J, Ortiz-Leyba C, Jiménez-Jiménez 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.
- 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.
- 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.
- 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.
- Evans ME, Feola DJ, Rapp RP. Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother 1999; 33:960.
- 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.
- Giacometti A, Cirioni O, Ghiselli R, et al. Antiendotoxin activity of antimicrobial peptides and glycopeptides. J Chemother 2003; 15:129.
- Warren HS, Kania SA, Siber GR. Binding and neutralization of bacterial lipopolysaccharide by colistin nonapeptide. Antimicrob Agents Chemother 1985; 28:107.
- Marchaim D, Chopra T, Pogue JM, et al. Outbreak of colistin-resistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan. Antimicrob Agents Chemother 2011; 55:593.
- Giani T, Arena F, Vaggelli G, et al. Large Nosocomial Outbreak of Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniae Traced to Clonal Expansion of an mgrB Deletion Mutant. J Clin Microbiol 2015; 53:3341.
- Capone A, Giannella M, Fortini D, et al. High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality. Clin Microbiol Infect 2013; 19:E23.
- Antoniadou A, Kontopidou F, Poulakou G, et al. Colistin-resistant isolates of Klebsiella pneumoniae emerging in intensive care unit patients: first report of a multiclonal cluster. J Antimicrob Chemother 2007; 59:786.
- Levin AS. Treatment of Acinetobacter spp infections. Expert Opin Pharmacother 2003; 4:1289.
- Arroyo LA, García-Curiel A, Pachón-Ibañez 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.
- 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.
- Lo-Ten-Foe JR, de Smet AM, Diederen BM, et al. Comparative evaluation of the VITEK 2, disk diffusion, etest, broth microdilution, and agar dilution susceptibility testing methods for colistin in clinical isolates, including heteroresistant Enterobacter cloacae and Acinetobacter baumannii strains. Antimicrob Agents Chemother 2007; 51:3726.
- 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.
- Tan TY, Ng SY. Comparison of Etest, Vitek and agar dilution for susceptibility testing of colistin. Clin Microbiol Infect 2007; 13:541.
- Groisman EA, Kayser J, Soncini FC. Regulation of polymyxin resistance and adaptation to low-Mg2+ environments. J Bacteriol 1997; 179:7040.
- 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.
- Adams MD, Nickel GC, Bajaksouzian S, et al. Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob Agents Chemother 2009; 53:3628.
- Li J, Rayner CR, Nation RL, et al. Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2006; 50:2946.
- Owen RJ, Li J, Nation RL, Spelman D. In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates. J Antimicrob Chemother 2007; 59:473.
- Liu YY, Wang Y, Walsh TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2016; 16:161.
- McGann P, Snesrud E, Maybank R, et al. Escherichia coli Harboring mcr-1 and blaCTX-M on a Novel IncF Plasmid: First Report of mcr-1 in the United States. Antimicrob Agents Chemother 2016; 60:4420.
- Poirel L, Kieffer N, Brink A, et al. Genetic Features of MCR-1-Producing Colistin-Resistant Escherichia coli Isolates in South Africa. Antimicrob Agents Chemother 2016; 60:4394.
- Doumith M, Godbole G, Ashton P, et al. Detection of the plasmid-mediated mcr-1 gene conferring colistin resistance in human and food isolates of Salmonella enterica and Escherichia coli in England and Wales. J Antimicrob Chemother 2016; 71:2300.
- 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.
- Karabinis A, Paramythiotou E, Mylona-Petropoulou D, et al. Colistin for Klebsiella pneumoniae-associated sepsis. Clin Infect Dis 2004; 38:e7.
- 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.
- Reed MD, Stern RC, O'Riordan MA, Blumer JL. The pharmacokinetics of colistin in patients with cystic fibrosis. J Clin Pharmacol 2001; 41:645.
- 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.
- Stein A, Raoult D. Colistin: an antimicrobial for the 21st century? Clin Infect Dis 2002; 35:901.
- Jiménez-Mejías ME, Pichardo-Guerrero C, Márquez-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.
- Markantonis SL, Markou N, Fousteri M, et al. Penetration of colistin into cerebrospinal fluid. Antimicrob Agents Chemother 2009; 53:4907.
- 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.
- Vasen W, Desmery P, Ilutovich S, Di Martino A. Intrathecal use of colistin. J Clin Microbiol 2000; 38:3523.
- 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.
- Nation RL, Li J. Polymyxins. In: The Use of Antibiotics, 6th Ed, Kucers A. (Ed), Heinemann, London 2010. p.955.
- Nation RL, Li J, Cars O, et al. Consistent global approach on reporting of colistin doses to promote safe and effective use. Clin Infect Dis 2014; 58:139.
- European Medicines Agency completes review of polymyxin-based medicines. December 2014. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2014/10/WC500176334.pdf (Accessed on May 08, 2016).
- Pogue JM, Ortwine JK, Kaye KS. Optimal Usage of Colistin: Are We Any Closer? Clin Infect Dis 2015; 61:1778.
- Nation RL, Garonzik SM, Li J, et al. Updated US and European Dose Recommendations for Intravenous Colistin: How Do They Perform? Clin Infect Dis 2016; 62:552.
- Vicari G, Bauer SR, Neuner EA, Lam SW. Association between colistin dose and microbiologic outcomes in patients with multidrug-resistant gram-negative bacteremia. Clin Infect Dis 2013; 56:398.
- Nation RL, Garonzik SM, Thamlikitkul V, et al. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis 2016.
- Dalfino L, Puntillo F, Mosca A, et al. High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study. Clin Infect Dis 2012; 54:1720.
- Trifi A, Abdellatif S, Daly F, et al. Efficacy and Toxicity of High-Dose Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections: A Comparative Study of a Matched Series. Chemotherapy 2016; 61:190.
- Benattar YD, Omar M, Zusman O, et al. The Effectiveness and Safety of High-Dose Colistin: Prospective Cohort Study. Clin Infect Dis 2016; 63:1605.
- Plachouras D, Karvanen M, Friberg LE, et al. Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrob Agents Chemother 2009; 53:3430.
- Garonzik SM, Li J, Thamlikitkul V, et al. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother 2011; 55:3284.
- Dalfino L, Puntillo F, Ondok MJ, et al. Colistin-associated Acute Kidney Injury in Severely Ill Patients: A Step Toward a Better Renal Care? A Prospective Cohort Study. Clin Infect Dis 2015; 61:1771.
- Solé-Lleonart C, Roberts JA, Chastre J, et al. Global survey on nebulization of antimicrobial agents in mechanically ventilated patients: a call for international guidelines. Clin Microbiol Infect 2016; 22:359.
- FDA Drug Safety Podcasts — Colistimethate (marketed as Coly-Mycin M and generic products) http://www.fda.gov/Drugs/DrugSafety/DrugSafetyPodcasts/ucm077907.htm (Accessed on December 06, 2011).
- Abdellatif S, Trifi A, Daly F, et al. Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: a prospective, randomised trial. Ann Intensive Care 2016; 6:26.
- Rattanaumpawan P, Lorsutthitham J, Ungprasert P, et al. Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by Gram-negative bacteria. J Antimicrob Chemother 2010; 65:2645.
- Liu D, Zhang J, Liu HX, et al. Intravenous combined with aerosolised polymyxin versus intravenous polymyxin alone in the treatment of pneumonia caused by multidrug-resistant pathogens: a systematic review and meta-analysis. Int J Antimicrob Agents 2015; 46:603.
- Kallel H, Hergafi L, Bahloul M, et al. Safety and efficacy of colistin compared with imipenem in the treatment of ventilator-associated pneumonia: a matched case-control study. Intensive Care Med 2007; 33:1162.
- 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.
- Linden PK, Paterson DL. Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clin Infect Dis 2006; 43 Suppl 2:S89.
- 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.
- 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.
- Pogue JM, Lee J, Marchaim D, et al. Incidence of and risk factors for colistin-associated nephrotoxicity in a large academic health system. Clin Infect Dis 2011; 53:879.
- Shields RK, Anand R, Clarke LG, et al. Defining the incidence and risk factors of colistin-induced acute kidney injury by KDIGO criteria. PLoS One 2017; 12:e0173286.
- Kim J, Lee KH, Yoo S, Pai H. Clinical characteristics and risk factors of colistin-induced nephrotoxicity. Int J Antimicrob Agents 2009; 34:434.
- Sirijatuphat R, Limmahakhun S, Sirivatanauksorn V, et al. Preliminary clinical study of the effect of ascorbic acid on colistin-associated nephrotoxicity. Antimicrob Agents Chemother 2015; 59:3224.
- 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.
- Wolinsky E, Hines JD. Neurotoxic and nephrotoxic effects of colistin in patients with renal disease. N Engl J Med 1962; 266:759.
- Lindesmith LA, Baines RD Jr, Bigelow DB, Petty TL. Reversible respiratory paralysis associated with polymyxin therapy. Ann Intern Med 1968; 68:318.
- Beringer P. The clinical use of colistin in patients with cystic fibrosis. Curr Opin Pulm Med 2001; 7:434.