Öz
Giriş: Kolistin, çok sayıda ilaca dirençli bakterilerin neden olduğu enfeksiyonların tedavisinde yaygın olarak kullanılmaktadır. Bu çalışmada, kolistin ilişkili nefrotoksisitenin sıklığı ve risk faktörlerinin belirlenmesi amaçlanmıştır.
Gereç ve Yöntem: Bu çalışmada Ekim 2018 ile Ağustos 2019 arasında, üçüncü basamak bir hastanede kolistin alan hastalar geriye dönük olarak incelenmiştir. Nefrotoksisitenin evrelenmesinde Kidney Disease: Improving Global Outcomes-Böbrek Hastalıkları: Küresel Sonuçların İyileştirilmesi kriterleri kullanılmıştır.
Bulgular: Çalışmaya kolistin ile tedavi edilen 100 hasta dahil edilmiştir. Hastaların ortanca yaşı 64 yıl ve %43’ü kadındır. Hastaların %52’sinde kolistin tedavisinin ilk haftasında nefrotoksisite saptanmıştır ve hastaların %59’unda kolistin tedavisinin herhangi bir anında nefrotoksisite saptanmıştır. Serum kreatinin ortanca dört (1-11) günde normal seviyenin ≥1,5 katına yükselmiştir ve ortanca beş (1-42) günde tahmini glomerüler filtrasyon hızı 60 ml/dakikanın altına düşmüştür. Kolistin tedavisine başlandıktan sonraki ilk haftanın sonunda hastaların %48’i “normal” böbrek fonksiyonlarını korumuştur. Kolistin tedavisine başladıktan sonraki ilk hafta nefrotoksisite gözlenen hastaların %20’si “evre 1”, %17’si “evre 2”, %15’i “evre 3” olarak saptanmıştır. Hastanede kalış süresi [Odds oranı (OR): 1,009; %95 güven aralığı (GA): 1,001-1,017], yaş (OR: 1,036; %95 GA: 1,005-1,068), kolistin tedavisi süresi (OR: 1,115, %95 GA: 1,023-1,216) ve vazopressör kullanımı (OR: 3,012, %95 GA: 1,003-9,042) kolistin tedavisinin herhangi bir anında nefrotoksisite ile ilişkilidir.
Sonuç: Bu çalışma, kolistin ile ilişkili nefrotoksisite oranının yüksek olduğunu göstermiştir. Özellikle vazopressörlerle birlikte uygulandığında böbrek fonksiyonlarının düzenli monitörizasyonu, uygun dozlama ve kolistin tedavi süresini mümkün olduğunca sınırlandırmak, yaşlı hastalarda nefrotoksisiteden kaçınmak için faydalı olabilir.
Anahtar Kelimeler: Polimiksinler, akut böbrek hasarı, nefrotoksisite, risk faktörü, kolistin dozu
Kaynakça
Suay-García B, Pérez-Gracia MT. Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections. Antibiotics (Basel). 2019;8:122.
Evans ME, Feola DJ, Rapp RP. Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother. 1999;33:960-7.
Zavascki AP, Nation RL. Nephrotoxicity of Polymyxins: Is There Any Difference between Colistimethate and Polymyxin B? Antimicrob Agents Chemother. 2017;61:e02319-16.
Falagas ME, Fragoulis KN, Kasiakou SK, Sermaidis GJ, Michalopoulos A. Nephrotoxicity of intravenous colistin: a prospective evaluation. Int J Antimicrob Agents. 2005;26:504-7.
Ordooei Javan A, Shokouhi S, Sahraei Z. A review on colistin nephrotoxicity. Eur J Clin Pharmacol. 2015;71:801-10.
Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis. 2005;40:1333-41.
Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, Silveira FP, Forrest A, Nation RL. 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;55:3284-94.
Nation RL, Garonzik SM, Li J, Thamlikitkul V, Giamarellos-Bourboulis EJ, Paterson DL, Turnidge JD, Forrest A, Silveira FP. Updated US and European Dose Recommendations for Intravenous Colistin: How Do They Perform? Clin Infect Dis. 2016;62:552-8.
Dalfino L, Puntillo F, Ondok MJ, Mosca A, Monno R, Coppolecchia S, Spada ML, Bruno F, Brienza N. Colistin-associated Acute Kidney Injury in Severely Ill Patients: A Step Toward a Better Renal Care? A Prospective Cohort Study. Clin Infect Dis. 2015;61:1771-7.
Omrani AS, Alfahad WA, Shoukri MM, Baadani AM, Aldalbahi S, Almitwazi AA, Albarrak AM. High dose intravenous colistin methanesulfonate therapy is associated with high rates of nephrotoxicity; a prospective cohort study from Saudi Arabia. Ann Clin Microbiol Antimicrob. 2015;14:3.
Deryke CA, Crawford AJ, Uddin N, Wallace MR. Colistin dosing and nephrotoxicity in a large community teaching hospital. Antimicrob Agents Chemother. 2010;54:4503-5.
Levin AS, Barone AA, Penço J, Santos MV, Marinho IS, Arruda EA, Manrique EI, Costa SF. Intravenous colistin as therapy for nosocomial infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Clin Infect Dis. 1999;28:1008-11.
Purnell JQ. Definitions, Classification, and Epidemiology of Obesity. 2018 Apr 12. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52:e56-93.
Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daikos GL, Forrest A, Giacobbe DR, Viscoli C, Giamarellou H, Karaiskos I, Kaye D, Mouton JW, Tam VH, Thamlikitkul V, Wunderink RG, Li J, Nation RL, Kaye KS. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39:10-39.
Kellum JA, Lameire N; KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care. 2013;17:204.
Shields RK, Anand R, Clarke LG, Paronish JA, Weirich M, Perone H, Kieserman J, Freedy H, Andrzejewski C, Bonilla H. Defining the incidence and risk factors of colistin-induced acute kidney injury by KDIGO criteria. PLoS One. 2017;12:e0173286.
Giacobbe DR, di Masi A, Leboffe L, Del Bono V, Rossi M, Cappiello D, Coppo E, Marchese A, Casulli A, Signori A, Novelli A, Perrone K, Principe L, Bandera A, Vender LE, Misin A, Occhilupo P, Melone M, Ascenzi P, Gori A, Luzzati R, Viscoli C, Di Bella S. Hypoalbuminemia as a predictor of acute kidney injury during colistin treatment. Sci Rep. 2018;8:11968.
Gunay E, Kaya S, Baysal B, Yuksel E, Arac E. Evaluation of prognosis and nephrotoxicity in patients treated with colistin in intensive care unit. Ren Fail. 2020;42:704-9.
Akajagbor DS, Wilson SL, Shere-Wolfe KD, Dakum P, Charurat ME, Gilliam BL. 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;57:1300-3.
Phe K, Lee Y, McDaneld PM, Prasad N, Yin T, Figueroa DA, Musick WL, Cottreau JM, Hu M, Tam VH. In vitro assessment and multicenter cohort study of comparative nephrotoxicity rates associated with colistimethate versus polymyxin B therapy. Antimicrob Agents Chemother. 2014;58:2740-6.
Balkan II, Dogan M, Durdu B, Batirel A, Hakyemez IN, Cetin B, Karabay O, Gonen I, Ozkan AS, Uzun S, Demirkol ME, Akbas S, Kacmaz AB, Aras S, Mert A, Tabak F. Colistin nephrotoxicity increases with age. Scand J Infect Dis. 2014;46:678-85.
Kwon JA, Lee JE, Huh W, Peck KR, Kim YG, Kim DJ, Oh HY. Predictors of acute kidney injury associated with intravenous colistin treatment. Int J Antimicrob Agents. 2010;35:473-7.
Ko Hj, Jeon Mh, Choo Ej, Lee Ej, Kim Th, Jun JB, Gil HW. Early acute kidney injury is a risk factor that predicts mortality in patients treated with colistin. Nephron Clin Pract. 2011;117:c284-8.
Katip W, Uitrakul S, Oberdorfer P. The effectiveness and nephrotoxicity of loading dose colistin combined with or without meropenem for the treatment of carbapenem-resistant A. baumannii. Int J Infect Dis. 2020;97:391-5.
Sorlí L, Luque S, Grau S, Berenguer N, Segura C, Montero MM, Alvarez-Lerma F, Knobel H, Benito N, Horcajada JP. Trough colistin plasma level is an independent risk factor for nephrotoxicity: a prospective observational cohort study. BMC Infect Dis. 2013;13:380.
Lee YJ, Wi YM, Kwon YJ, Kim SR, Chang SH, Cho S. Association between colistin dose and development of nephrotoxicity. Crit Care Med. 2015;43:1187-93.
Chen YY, Wu VC, Huang WC, Yeh YC, Wu MS, Huang CC, Wu KD, Fang JT, Wu CJ; NSARF; CAKS Group. Norepinephrine Administration Is Associated with Higher Mortality in Dialysis Requiring Acute Kidney Injury Patients with Septic Shock. J Clin Med. 2018;7:274.
Bellomo R, Wan L, May C. Vasoactive drugs and acute kidney injury. Crit Care Med. 2008;36(4 Suppl):S179-86.
Bugano DDG, Cavalcanti AB, Goncalves AR, Almeida CSD, Silva E. Meta-análise Cochrane: teicoplanina versus vancomicina para infecções suspeitas ou confirmadas. Einstein (São Paulo). 2011;9:265-82.
Hartzell JD, Neff R, Ake J, Howard R, Olson S, Paolino K, Vishnepolsky M, Weintrob A, Wortmann G. Nephrotoxicity associated with intravenous colistin (colistimethate sodium) treatment at a tertiary care medical center. Clin Infect Dis. 2009;48:1724-8.
Aggarwal R, Dewan A. Comparison of nephrotoxicity of Colistin with Polymyxin B administered in currently recommended doses: a prospective study. Ann Clin Microbiol Antimicrob. 2018;17:15.
Temocin F, Erdinc S, Tulek N, Demirelli M, Bulut C, Ertem G. Incidence and Risk Factors for Colistin-Associated Nephrotoxicity. Jpn J Infect Dis. 2015;68:318-20.
