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A review on colistin nephrotoxicity

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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Colistin is an antibiotic that was introduced many years ago and was withdrawn because of its nephrotoxicity. Nowadays, reemergence of this antibiotic for multi-drug resistant Gram-negative infections, and a new high dosing regimen recommendation increases concern about its nephrotoxicity. This review attempts to give a view on colistin nephrotoxicity, its prevalence especially in high doses, the mechanism of injury, risk factors, and prevention of this kidney injury.

Method

The data collection was done in PubMed, Scopus and Cochrane databases. The keywords for search terms were “colistin”, “nephrotoxicity”, “toxicity”, “renal failure”, “high dose”, and “risk factor”. Randomized clinical trials and prospective or retrospective observational animal and human studies were included. In all, 60 articles have been reviewed.

Result and conclusion

Colistin is a nephrotoxic antibiotic; a worldwide increase in nosocomial infections has led to an increase in its usage. Nephrotoxicity is the concerning adverse effect of this drug. The mechanism of nephrotoxicity is via an increase in tubular epithelial cell membrane permeability, which results in cation, anion and water influx leading to cell swelling and cell lysis. There are also some oxidative and inflammatory pathways that seem to be involved in colistin nephrotoxicity. Risk factors of colistin nephrotoxicity can be categorized as dose and duration of colistin therapy, co-administration of other nephrotoxic drugs, and patient-related factors such as age, sex, hypoalbuminemia, hyperbilirubinemia, underlying disease and severity of patient illness.

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References

  1. Falagas ME, Kasiakou SK, Saravolatz LD (2005) Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis 40(9):1333–1341

    Article  CAS  PubMed  Google Scholar 

  2. Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, Paterson DL (2006) Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis 6(9):589–601

    Article  CAS  PubMed  Google Scholar 

  3. Nation RL, Li J (2009) Colistin in the 21st century. Curr Opin Infect Dis 22(6):535

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Lim LM, Ly N, Anderson D, Yang JC, Macander L, Jarkowski A, Forrest A, Bulitta JB, Tsuji BT (2010) Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacother J Human Pharmacol Drug Ther 30(12):1279–1291

    Article  CAS  Google Scholar 

  5. John E, Bennett RD, Blaser MJ (2015) Polymyxins (Polymyxin B and Colistin). In: Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 8 edn. Elsevier Saunders, Canada, pp 549–555

  6. Florescu DF, Qiu F, McCartan MA, Mindru C, Fey PD, Kalil A (2012) What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression. Clin Infect Dis 54(5):670–680

    Article  CAS  PubMed  Google Scholar 

  7. Bergen PJ, Li J, Rayner CR, Nation RL (2006) Colistin methanesulfonate is an inactive prodrug of colistin against Pseudomonas aeruginosa. Antimicrob Agents Chemother 50(6):1953–1958

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Mendes CAC, Burdmann EA (2009) Polymyxins: review with emphasis on nephrotoxicity. Rev Assoc Med Bras 55(6):752–759

    Article  PubMed  Google Scholar 

  9. Michalopoulos AS, Falagas ME (2011) Colistin: recent data on pharmacodynamics properties and clinical efficacy in critically ill patients. Ann Intensive Care 1(1):1–6

    Article  Google Scholar 

  10. Plachouras D, Karvanen M, Friberg L, Papadomichelakis E, Antoniadou A, Tsangaris I, Karaiskos I, Poulakou G, Kontopidou F, Armaganidis A (2009) 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 53(8):3430–3436

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Hartzell JD, Neff R, Ake J, Howard R, Olson S, Paolino K, Vishnepolsky M, Weintrob A, Wortmann G (2009) Nephrotoxicity associated with intravenous colistin (colistimethate sodium) treatment at a tertiary care medical center. Clin Infect Dis 48(12):1724–1728

    Article  CAS  PubMed  Google Scholar 

  12. DeRyke CA, Crawford AJ, Uddin N, Wallace MR (2010) Colistin dosing and nephrotoxicity in a large community teaching hospital. Antimicrob Agents Chemother 54(10):4503–4505

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Paul M, Bishara J, Levcovich A, Chowers M, Goldberg E, Singer P, Lev S, Leon P, Raskin M, Yahav D (2010) Effectiveness and safety of colistin: prospective comparative cohort study. J Antimicrob Chemother 65(5):1019–1027

    Article  CAS  PubMed  Google Scholar 

  14. Markou N, Apostolakos H, Koumoudiou C, Athanasiou M, Koutsoukou A, Alamanos I, Gregorakos L (2003) Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients. Crit Care 7(5):R78

    Article  PubMed Central  PubMed  Google Scholar 

  15. Pintado V, San Miguel LG, Grill F, Mejía B, Cobo J, Fortún J, Martín-Dávila P, Moreno S (2008) Intravenous colistin sulphomethate sodium for therapy of infections due to multidrug-resistant gram-negative bacteria. J Infect 56(3):185–190

    Article  PubMed  Google Scholar 

  16. Betrosian AP, Frantzeskaki F, Xanthaki A, Douzinas EE (2008) Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii  ventilator-associated pneumonia. J Infect 56(6):432–436

    Article  PubMed  Google Scholar 

  17. Dalfino L, Puntillo F, Mosca A, Monno R, Spada ML, Coppolecchia S, Miragliotta G, Bruno F, Brienza N (2012) High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study. Clin Infect Dis 54(12):1720–1726

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Tuon FF, Rigatto MH, Lopes CK, Kamei LK, Rocha JL, Zavascki AP (2014) Risk factors for acute kidney injury in patients treated with polymyxin B or colistin methanesulfonate sodium. Int J Antimicrob Agents 43(4):349–352

    Article  CAS  PubMed  Google Scholar 

  19. Pogue JM, Lee J, Marchaim D, Yee V, Zhao JJ, Chopra T, Lephart P, Kaye KS (2011) Incidence of and risk factors for colistin-associated nephrotoxicity in a large academic health system. Clin Infect Dis 53(9):879–884

    Article  CAS  PubMed  Google Scholar 

  20. Rocco M, Montini L, Alessandri E, Venditti M, Laderchi A, De Pascale G, Raponi G, Vitale M, Pietropaoli P, Antonelli M (2013) Risk factors for acute kidney injury in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics: a retrospective cohort study. Crit Care 17:R174

    Article  PubMed Central  PubMed  Google Scholar 

  21. Sorlí L, Luque S, Grau S, Berenguer N, Segura C, Montero MM, Álvarez-Lerma F, Knobel H, Benito N, Horcajada JP (2013) Trough colistin plasma level is an independent risk factor for nephrotoxicity: a prospective observational cohort study. BMC Infect Dis 13(1):1–9

    Article  Google Scholar 

  22. Kalin G, Alp E, Coskun R, Demiraslan H, Gündogan K, Doganay M (2012) Use of high-dose IV and aerosolized colistin for the treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia: do we really need this treatment? J Infect Chemother 18(6):872–877

    Article  CAS  PubMed  Google Scholar 

  23. Duraković N, Radojčić V, Boban A, Mrsić M, Sertić D, Serventi-Seiwerth R, Nemet D, Labar B (2011) Efficacy and safety of colistin in the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa in patients with hematologic malignancy: a matched pair analysis. Intern Med (Tokyo, Japan) 50(9):1009–1013

    Article  Google Scholar 

  24. Kallel H, Bahloul M, Hergafi L, Akrout M, Ketata W, Chelly H, Hamida CB, Rekik N, Hammami A, Bouaziz M (2006) Colistin as a salvage therapy for nosocomial infections caused by multidrug-resistant bacteria in the ICU. Int J Antimicrob Agents 28(4):366–369

    Article  CAS  PubMed  Google Scholar 

  25. Luque S, Grau S, Valle M, Sorlí L, Horcajada JP, Segura C, Álvarez-Lerma F (2013) Differences in pharmacokinetics and pharmacodynamics of colistimethate sodium (CMS) and colistin between three different CMS dosage regimens in a critically ill patient infected by a multidrug-resistant < i > Acinetobacter baumannii</i> Int J Antimicrob Agents 42(2):178–181

    Article  CAS  PubMed  Google Scholar 

  26. Imberti R, Cusato M, Villani P, Carnevale L, Iotti GA, Langer M, Regazzi M (2010) Steady-state pharmacokinetics and BAL concentration of colistin in critically ill patients after IV colistin methanesulfonate administration. Chest J 138(6):1333–1339

    Article  CAS  Google Scholar 

  27. Cheng C-Y, Sheng W-H, Wang J-T, Chen Y-C, Chang S-C (2010) Safety and efficacy of intravenous colistin (colistin methanesulphonate) for severe multidrug-resistant Gram-negative bacterial infections. Int J Antimicrob Agents 35(3):297–300

    Article  CAS  PubMed  Google Scholar 

  28. Roberts JA, Lipman J (2012) Editorial commentary: closing the loop—a colistin clinical study to confirm dosing recommendations from PK/PD modeling. Clin Infect Dis 54(12):1727–1729

    Article  CAS  PubMed  Google Scholar 

  29. Li J, Nation RL, Milne RW, Turnidge JD, Coulthard K (2005) Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria. Int J Antimicrob Agents 25(1):11–25

    Article  PubMed  Google Scholar 

  30. Zavascki AP, Goldani LZ, Li J, Nation RL (2007) Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother 60(6):1206–1215

    Article  CAS  PubMed  Google Scholar 

  31. Falagas ME, Kasiakou SK (2006) Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 10(1):R27

    Article  PubMed Central  PubMed  Google Scholar 

  32. Spapen H, Jacobs R, Van Gorp V, Troubleyn J, Honoré PM (2011) Renal and neurological side effects of colistin in critically ill patients. Ann Intensive Care 1(1):1–7

    Article  Google Scholar 

  33. Garnacho-Montero J, Ortiz-Leyba C, Jimenez-Jimenez F, Barrero-Almodovar A, Garcia-Garmendia J, Bernabeu-Wittell M, Gallego-Lara S, Madrazo-Osuna J (2003) Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: a comparison with imipenem-susceptible VAP. Clin Infect Dis 36(9):1111–1118

    Article  CAS  PubMed  Google Scholar 

  34. Kim J, Lee K-H, Yoo S, Pai H (2009) Clinical characteristics and risk factors of colistin-induced nephrotoxicity. Int J Antimicrob Agents 34(5):434–438

    Article  CAS  PubMed  Google Scholar 

  35. Kofteridis DP, Alexopoulou C, Valachis A, Maraki S, Dimopoulou D, Georgopoulos D, Samonis G (2010) Aerosolized plus intravenous colistin versus intravenous colistin alone for the treatment of ventilator-associated pneumonia: a matched case–control study. Clin Infect Dis 51(11):1238–1244

    Article  CAS  PubMed  Google Scholar 

  36. Linden PK, Kusne S, Coley K, Fontes P, Kramer DJ, Paterson D (2003) Use of parenteral colistin for the treatment of serious infection due to antimicrobial-resistant Pseudomonas aeruginosa. Clin Infect Dis 37(11):e154–e160

    Article  CAS  PubMed  Google Scholar 

  37. Linden PK, Paterson DL (2006) Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clin Infect Dis 43(Supplement 2):S89–S94

    Article  CAS  PubMed  Google Scholar 

  38. Honoré PM, Jacobs R, Joannes-Boyau O, Lochy S, Boer W, De Waele E, Van Gorp V, De Regt J, Collin V, Spapen HD (2014) Continuous renal replacement therapy-related strategies to avoid colistin toxicity: a clinically orientated review. Blood Purif 37(4):291–295

    Article  PubMed  Google Scholar 

  39. Falagas ME, Fragoulis KN, Kasiakou SK, Sermaidis GJ, Michalopoulos A (2005) Nephrotoxicity of intravenous colistin: a prospective evaluation. Int J Antimicrob Agents 26(6):504–507

    Article  CAS  PubMed  Google Scholar 

  40. Katz R (1963) Renal and possibly hepatic toxicity from coly-mycin. Report of a case. Med Ann Dist Columbia 32:408

    CAS  PubMed  Google Scholar 

  41. Ozkan G, Ulusoy S, Orem A, Alkanat M, Mungan S, Yulug E, Yucesan FB (2013) How does colistin-induced nephropathy develop and can it be treated? Antimicrob Agents Chemother 57(8):3463–3469

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Ko H, Jeon M, Choo E, Lee E, Kim T, Jun J-B, Gil H-W (2010) Early acute kidney injury is a risk factor that predicts mortality in patients treated with colistin. Nephron Clin Pract 117(3):c284–c288

    Article  PubMed  Google Scholar 

  43. Rattanaumpawan P, Ungprasert P, Thamlikitkul V (2011) Risk factors for colistin-associated nephrotoxicity. J Infect 62(2):187–190

    Article  PubMed  Google Scholar 

  44. Kwon J-A, Lee JE, Huh W, Peck KR, Kim Y-G, Kim DJ, Oh HY (2010) Predictors of acute kidney injury associated with intravenous colistin treatment. Int J Antimicrob Agents 35(5):473–477

    Article  CAS  PubMed  Google Scholar 

  45. Doshi NM, Mount KL, Murphy CV (2011) Nephrotoxicity associated with intravenous colistin in critically ill patients. Pharmacother J Human Pharmacol Drug Ther 31(12):1257–1264

    Article  Google Scholar 

  46. Kift EV, Maartens G, Bamford C (2014) Systematic review of the evidence for rational dosing of colistin. SAMJ: South African Med J 104(3):183–186

    Article  Google Scholar 

  47. Garonzik S, Li J, Thamlikitkul V, Paterson D, Shoham S, Jacob J, Silveira F, Forrest A, Nation R (2011) 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 55(7):3284–3294

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Shavit L, Manilov R, Wiener-Well Y, Algur N, Slotki I (2013) Urinary neutrophil gelatinase-associated lipocalin for early detection of acute kidney injury in geriatric patients with urinary tract infection treated by colistin. Clin Nephrol 80(6):405–416

    Article  CAS  PubMed  Google Scholar 

  49. Han WK, Bonventre JV (2004) Biologic markers for the early detection of acute kidney injury. Curr Opin Crit Care 10(6):476–482

    Article  PubMed  Google Scholar 

  50. Ghlissi Z, Hakim A, Mnif H, Ayadi FM, Zeghal K, Rebai T, Sahnoun Z (2013) Evaluation of colistin nephrotoxicity administered at different doses in the rat model. Ren Fail 35(8):1130–1135

    Article  CAS  PubMed  Google Scholar 

  51. Soni SS, Ronco C, Katz N, Cruz DN (2009) Early diagnosis of acute kidney injury: the promise of novel biomarkers. Blood Purif 28(3):165–174

    Article  CAS  PubMed  Google Scholar 

  52. Keirstead ND, Wagoner MP, Bentley P, Blais M, Brown C, Cheatham L, Ciaccio P, Dragan Y, Ferguson D, Fikes J (2014) Early prediction of polymyxin-induced nephrotoxicity with next-generation urinary kidney injury biomarkers. Toxicol Sci 137(2):278–291

    Article  CAS  PubMed  Google Scholar 

  53. http://www.irct.ir/searchresult.php?keyword=colistin&id=14693&number=5&field=g&prt=2&total=2&m=1 (2014) Zahra Sahraei. Accessed 23 Sept 2014

  54. Ozyilmaz E, Ebinc FA, Derici U, Gulbahar O, Goktas G, Elmas C, Oguzulgen IK, Sindel S (2011) Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine? Intensive Care Med 37(1):141–146

    Article  CAS  PubMed  Google Scholar 

  55. Yousef JM, Chen G, Hill PA, Nation RL, Li J (2011) Melatonin attenuates colistin-induced nephrotoxicity in rats. Antimicrob Agents Chemother 55(9):4044–4049

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Yousef JM, Chen G, Hill PA, Nation RL, Li J (2011) Ascorbic acid protects against the nephrotoxicity and apoptosis caused by colistin and affects its pharmacokinetics. J Antimicrob Chemotherapy:dkr483

  57. Ghlissi Z, Hakim A, Sila A, Mnif H, Zeghal K, Rebai T, Bougatef A, Sahnoun Z (2014) Evaluation of efficacy of natural astaxanthin and vitamin E in prevention of colistin-induced nephrotoxicity in the rat model. Environ Toxicol Pharmacol 37(3):960–966

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Niyayesh Cross Road, Valiasr Street, Tehran, Iran

    Atefeh Ordooei Javan & Zahra Sahraei

  2. Department of Infectious Disease, Loghman Hospital, Shahid Beheshti University of Medical Sciences, Lashkar Intersection, Kargar Street, Tehran, Iran

    Shervin Shokouhi

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  1. Atefeh Ordooei Javan
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Correspondence to Zahra Sahraei.

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Ordooei Javan, A., Shokouhi, S. & Sahraei, Z. A review on colistin nephrotoxicity. Eur J Clin Pharmacol 71, 801–810 (2015). https://doi.org/10.1007/s00228-015-1865-4

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