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Purpose: Vancomycin-induced nephrotoxicity has been associated with total body weight (TBW) ≥101 kg and total daily doses (TDD) ≥4 grams. We hypothesized that nephrotoxicity is not associated with TBW ≥101 kg or TDD ≥4 grams when vancomycin is dosed to achieve trough concentrations of 15-20 mg/L.
Methods: A retrospective case-control study was conducted at two academic medical centers. Obese (TBW ≥101 kg) and non-obese (TBW <101 kg) patients were included based on age ≥18 years, ≥48 hours of vancomycin therapy, baseline serum creatinine (SCr) <2.0 mg/dL, and ≥1 vancomycin trough level. Exclusion criteria included cystic fibrosis, unstable renal function, renal replacement therapy, or IV contrast dye within 7 days of starting vancomycin. Nephrotoxicity was defined as SCr increased >0.5 mg/dL or >50% over baseline on ≥2 consecutive days after initiating vancomycin.
Results: A total of 116 obese (mean ± SD 122.0 ± 20.1 kg, range 101.0 to 205.0 kg) and 115 non-obese patients (72.8 ± 12.9 kg, range 44.5 to 99.1 kg) were evaluated. Nephrotoxicity occurred in 9% (10/116) of obese and 10% (12/115) of non-obese patients (p=0.661; OR 0.81; 95% CI 0.33, 1.96). Nephrotoxicity occurred in 4/37 patients (11%) receiving TDD ≥4 grams versus 18/194 (9%) in patients receiving <4 grams/day (p=0.761; OR 0.1.18; 95% CI 0.38, 3.73). Thirty-one obese patients (27%) required TDD ≥4 grams to achieve troughs of 15-20 mg/L compared to 6 non-obese patients (5%); nephrotoxicity occurred in 3/31 (10%) and 1/6 (16%) of obese and non-obese patients, respectively (p=0.523; OR 0.53; 95% CI 0.04, 6.2). Nephrotoxicity was not significantly associated with TBW (p=0.702), TDD on Day 1 of therapy (P=0.738), or TDD during maintenance dosing (p=0.765).
Conclusion: Obese patients and those requiring TDD ≥4 grams are not at significantly increased risk of vancomycin-induced nephrotoxicity when dosed to achieve recommended trough concentrations of 15-20 mg/L.