A Study on Acute Kidney Injury Caused by Intravenous Colistimethate in Critically Ill Patients

중환자에서 Colistimethate 정맥내 투여와 관련된 급성 신손상에 대한 연구

  • Oh, Myunghyun (Graduate School of Clinical pharmacy, Sookmyung Women's University) ;
  • Bang, Joon Seok (Graduate School of Clinical pharmacy, Sookmyung Women's University)
  • 오명현 (숙명여자대학교 임상약학대학원) ;
  • 방준석 (숙명여자대학교 임상약학대학원)
  • Received : 2013.11.28
  • Accepted : 2013.12.23
  • Published : 2013.12.31

Abstract

Objective: Colistimethate was first became available in 1950s and used until the early 1980s to treat infections caused by gram-negative bacteria and was abandoned due to its nephrotoxicity and neurotoxicity. However, it was recently reintroduced into the clinical practices due to emergence of multidrug-resistance gram-negative bacteria, particularly Pseudomonas aeruginosa and Acinetobacter baumanii. Therefore, it is increasingly used in the intensive care unit settings as a salvage therapy. This study was designed to investigate the incidence rates and risk factors of acute kidney injury associated with colistimethate by using the standardized definition in critically ill patients. Methods: This study retrospectively reviewed the electronic medical records of 71 adult patients above 18 years old receiving intravenous colistimethate at least 48 hours at intensive care unit, university-affiliated hospital from Nov 2012 to Aug 2013 and excluded patients with end-stage renal disease (ESRD) and required renal replacement therapy before initiation of the colistimethate therapy. Acute kidney injury (AKI) was determined by using the standardized RIFLE criteria, classified with risk, injury, failure, loss and ESRD according to serum creatinine (Scr) levels. Results: Among the 71 patients included in the analysis, AKI developed in 40 patients (56.3%) and 6 patients (8.4%) had irreversible kidney injury. AKI occurred within 5 days in 20 patients (50.0%). Maximum Scr level showed a significant increase in the patients with AKI ($1.92{\pm}0.86mg/dL$ vs. $1.12{\pm}0.46mg/dL$ p=0.001), maximum BUN also increased ($64.2{\pm}28.7mg/dL$ vs. $48.4{\pm}24.9mg/dL$ p=0.017) and minimum creatinine clearance (CLcr) was significantly decreased in the patients with AKI than non-AKI ($34.5{\pm}18.6ml/min$ vs. $64.4{\pm}33.7ml/min$ p=0.185). The patients with AKI had significantly longer duration of colistimethate therapy ($21.1{\pm}17.0$ days vs. $13.0{\pm}11.5$ days, p=0.020) and larger cumulative doses of colistimethate ($6465.9{\pm}4717.0mg$ vs. $4438.1{\pm}3426.7mg$, p=0.040). Conclusion: The incidence and severity of AKI associated with colistimethate in critically ill patients was high and serious. Drug monitoring program should be performed to shorten duration of therapy and reduce cumulative dose from initiation of colistimethate therapy for minimizing AKI of colistimethate.

Keywords

References

  1. 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 (12): 1724-8. https://doi.org/10.1086/599225
  2. Schindler M, Osborn MJ. Interaction of divalent cations and polymyxin B with lipopolysaccharide. Biochemistry 1979; 18(20): 4425-30. https://doi.org/10.1021/bi00587a024
  3. Brown JM, Dorman DC, Roy LP. Acute renal failure due to overdosage of colistin. Med J Aust 1970; 2(20): 923-4.
  4. Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Critical care 2006; 10(1): R27. https://doi.org/10.1186/cc3995
  5. Micromedex2.0. Colistimethate sodium. http://www.micromedexsolutions.com/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/CS/B39688/ND_AppProduct/evidencexpert/DUPLICATIONSHIELDSYNC/E32768/ND_PG/evidencexpert/ND_B/evidencexpert/ND_P/evidencexpert/PFActionId/evidencexpert.IntermediateToDocumentLink?docId=2708&contentSetId=31&title=COLISTIMETHATE+SODIUM&servicesTitle=COLISTIMETHATE+SODIUM (Accessed Oct 31, 2013).
  6. 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(6): 857-68. https://doi.org/10.7326/0003-4819-72-6-857
  7. Goverman J, Weber JM, Keaney TJ, et al. Intravenous colistin for the treatment of multi-drug resistant, gramnegative infection in the pediatric burn population. J Burn Care Res 2007; 28(3): 421-6. https://doi.org/10.1097/BCR.0B013E318053D346
  8. 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(7): 1162-7. https://doi.org/10.1007/s00134-007-0675-2
  9. Levin AS, Barone AA, Penco J, et al. Intravenous colistin as therapy for nosocomial infections caused by multidrugresistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin Infect Dis 1999; 28(5): 1008-11. https://doi.org/10.1086/514732
  10. 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(11): e154-60. https://doi.org/10.1086/379611
  11. Berg JR, Spilker CM, Lewis SA. Modulation of polymyxin B effects on mammalian urinary bladder. Am J Physiol 1998; 275(2Pt2): F204-15.
  12. Gaynes R, Edwards JR. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 2005; 41(6): 848-54. https://doi.org/10.1086/432803
  13. Gales AC, Jones RN, Sader HS. Contemporary activity of colistin and polymyxin B against a worldwide collection of Gram-negative pathogens: results from the SENTRY Antimicrobial Surveillance Program (2006-09). J Antimicrob Chemother 2011; 66(9): 2070-4. https://doi.org/10.1093/jac/dkr239
  14. Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis 2005; 40(9): 1333-41. https://doi.org/10.1086/429323
  15. Markou N, Apostolakos H, Koumoudiou C, et al. Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients. Critical care 2003; 7(5): R78-83. https://doi.org/10.1186/cc2358
  16. Kallel H, Bahloul M, Hergafi L, et al. Colistin as a salvage therapy for nosocomial infections caused by multidrug-resistant bacteria in the ICU. Int J Antimicrob Agents 2006; 28(4): 366-9. https://doi.org/10.1016/j.ijantimicag.2006.07.008
  17. 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(1): 11-25. https://doi.org/10.1016/j.ijantimicag.2004.10.001
  18. Livermore DM. The need for new antibiotics. Clin Microbiol Infect 2004; 10 Suppl 4 :1-9.
  19. Falagas ME, Fragoulis KN, Kasiakou SK, et al. Nephrotoxicity of intravenous colistin: a prospective evaluation. Int J Antimicrob Agents 2005; 26(6): 504-7. https://doi.org/10.1016/j.ijantimicag.2005.09.004
  20. Falagas ME, Kasiakou SK, Kofteridis DP, et al. Effectiveness and nephrotoxicity of intravenous colistin for treatment of patients with infections due to polymyxin-onlysusceptible (POS) gram-negative bacteria. Eur J Clin Microbiol Infect Dis 2006; 25(9): 596-9. https://doi.org/10.1007/s10096-006-0191-2
  21. Kasiakou SK, Michalopoulos A, Soteriades ES, et al. Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gramnegative bacteria in patients without cystic fibrosis. Antimicrob Agents Chemother 2005; 49(8): 3136-46. https://doi.org/10.1128/AAC.49.8.3136-3146.2005
  22. Landman D, Georgescu C, Martin DA, et al. Polymyxins revisited. Clin Microbiol Rev 2008; 21(3): 449-65. https://doi.org/10.1128/CMR.00006-08
  23. Spapen H, Jacobs R, Van Gorp V, et al. Renal and neurological side effects of colistin in critically ill patients. Ann Intensive Care 2011; 1(1): 14. https://doi.org/10.1186/2110-5820-1-14
  24. Doshi NM, Mount KL, Murphy CV. Nephrotoxicity associated with intravenous colistin in critically ill patients. Pharmacotherapy 2011; 31(12): 1257-64. https://doi.org/10.1592/phco.31.12.1257
  25. Kim J, Lee KH, Yoo S, et al. Clinical characteristics and risk factors of colistin-induced nephrotoxicity. Int J Antimicrob Agents 2009; 34(5): 434-8. https://doi.org/10.1016/j.ijantimicag.2009.06.028
  26. Kwon JA, Lee JE, Huh W, et al. Predictors of acute kidney injury associated with intravenous colistin treatment. Int J Antimicrob Agents 2010; 35(5): 473-7. https://doi.org/10.1016/j.ijantimicag.2009.12.002
  27. Kellum JA, Bellomo R, Ronco C. Definition and classification of acute kidney injury. Nephron Clin Pract 2008; 109(4): c182-7. https://doi.org/10.1159/000142926
  28. Deryke CA, Crawford AJ, Uddin N, et al. Colistin dosing and nephrotoxicity in a large community teaching hospital. Antimicrob Agents Chemother 2010; 54(10): 4503-5. https://doi.org/10.1128/AAC.01707-09
  29. Montero M, Horcajada JP, Sorli L, et al. Effectiveness and safety of colistin for the treatment of multidrug-resistant Pseudomonas aeruginosa infections. Infection 2009; 37(5): 461-5. https://doi.org/10.1007/s15010-009-8342-x
  30. Akajagbor DS, Wilson SL, Shere-Wolfe KD, et al. Higher Incidence of Acute Kidney Injury With Intravenous Colistimethate Sodium Compared With Polymyxin B in Critically Ill Patients at a Tertiary Care Medical Center. Clin Infect Dis 2013; 57(9): 1300-3. https://doi.org/10.1093/cid/cit453
  31. Reina R, Estenssoro E, Saenz G, et al. Safety and efficacy of colistin in Acinetobacter and Pseudomonas infections: a prospective cohort study. Intensive care med 2005; 31(8): 1058-65. https://doi.org/10.1007/s00134-005-2691-4
  32. 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(2): 115-21. https://doi.org/10.1111/j.1469-0691.2004.01043.x
  33. Nam WJ, Shin JH, Han MJ, et al. Clinical significance of acute kidney injury in patients with colistin treatment. Korean J Nephrol 2011; 30: 484-9.
  34. Imberti R, Cusato M, Villani P, et al. Steady-state pharmacokinetics and BAL concentration of colistin in critically Ill patients after IV colistin methanesulfonate administration. Chest 2010; 138(6): 1333-9. https://doi.org/10.1378/chest.10-0463
  35. Rattanaumpawan P, Ungprasert P, Thamlikitkul V. Risk factors for colistin-associated nephrotoxicity. J Infect 2011; 62(2): 187-90. https://doi.org/10.1016/j.jinf.2010.11.013
  36. Ko H, Jeon M, Choo E, et al. Early acute kidney injury is a risk factor that predicts mortality in patients treated with colistin. Nephron Clin Pract 2011; 117(3): c284-8. https://doi.org/10.1159/000320746
  37. Kidney function tests. MedlinePlus. http://www.nlm.nih.gov/medlineplus/ency/article/003435.htm (Accessed NOV 05, 2013).