Yanina Dubrovskaya1, Nishant Prasad2, Yuman Lee3, Diana Esaian1, Deborah A Figueroa4, Vincent H Tam5. 1. Department of Pharmacy, New York University Langone Medical Center, New York, NY, USA. 2. The Dr. James J. Rahal, Jr. Division of Infectious Diseases, New York Hospital Queens, Flushing, NY, USA. 3. Department of Pharmacy, Maimonides Medical Center, Brooklyn, NY, USA. 4. Department of Pharmacy, New York Hospital Queens, Flushing, NY, USA. 5. Department of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, TX, USA vtam@uh.edu.
Abstract
OBJECTIVES: Polymyxin B is an active agent against many MDR Gram-negative bacteria, but nephrotoxicity is a major hindrance to its widespread use. To guide its optimal use, we determined the risk factors for nephrotoxicity onset associated with polymyxin B. METHODS: In a multicentre, retrospective, cohort study, we evaluated adult patients with normal renal function who received ≥72 h of polymyxin B therapy. Pertinent information was retrieved from medical records; patients were followed for up to 30 days after therapy was started. The primary endpoint of this study was the onset of nephrotoxicity. A Cox proportional hazards model was used for analysis. RESULTS: A total of 192 patients (52.1% male, 67.7% Caucasian) were evaluated. The mean ± SD age, actual body weight (ABW) and daily dose by ABW were 68.3 ± 17.2 years, 71.5 ± 20.4 kg and 1.5 ± 0.5 mg/kg, respectively. The median duration of therapy was 9.5 days. The overall prevalence rate of nephrotoxicity was 45.8% and the median onset of nephrotoxicity was 9 days. Independent risk factors for the onset of nephrotoxicity included daily dose by ABW (HR = 1.73; P = 0.022), concurrent use of vancomycin (HR = 1.89; P = 0.005) and contrast media (HR = 1.79; P = 0.009). Nephrotoxicity was seen earlier in the high-risk group (P = 0.003). CONCLUSIONS: Risk factors for nephrotoxicity onset associated with polymyxin B were identified. In conjunction with susceptibility and other pharmacokinetic/pharmacodynamic data, our results can be used to optimize treatment for MDR Gram-negative infections.
OBJECTIVES: Polymyxin B is an active agent against many MDR Gram-negative bacteria, but nephrotoxicity is a major hindrance to its widespread use. To guide its optimal use, we determined the risk factors for nephrotoxicity onset associated with polymyxin B. METHODS: In a multicentre, retrospective, cohort study, we evaluated adult patients with normal renal function who received ≥72 h of polymyxin B therapy. Pertinent information was retrieved from medical records; patients were followed for up to 30 days after therapy was started. The primary endpoint of this study was the onset of nephrotoxicity. A Cox proportional hazards model was used for analysis. RESULTS: A total of 192 patients (52.1% male, 67.7% Caucasian) were evaluated. The mean ± SD age, actual body weight (ABW) and daily dose by ABW were 68.3 ± 17.2 years, 71.5 ± 20.4 kg and 1.5 ± 0.5 mg/kg, respectively. The median duration of therapy was 9.5 days. The overall prevalence rate of nephrotoxicity was 45.8% and the median onset of nephrotoxicity was 9 days. Independent risk factors for the onset of nephrotoxicity included daily dose by ABW (HR = 1.73; P = 0.022), concurrent use of vancomycin (HR = 1.89; P = 0.005) and contrast media (HR = 1.79; P = 0.009). Nephrotoxicity was seen earlier in the high-risk group (P = 0.003). CONCLUSIONS: Risk factors for nephrotoxicity onset associated with polymyxin B were identified. In conjunction with susceptibility and other pharmacokinetic/pharmacodynamic data, our results can be used to optimize treatment for MDR Gram-negative infections.
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