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

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.

중환자에서 Colistimethate 정맥내 투여와 관련된 급성 신손상에 대한 연구