Risk factors for nephrotoxicity associated with continuous vancomycin infusion in outpatient parenteral antibiotic therapy

Objectives: Continuous vancomycin infusion is increasingly used for outpatient management of infections, but the relationship between vancomycin and nephrotoxicity is controversial. We investigated the risk factors associated with nephrotoxicity in this setting. Methods: A retrospective cohort study of patients receiving continuous vancomycin infusion as outpatient parenteral antibiotic therapy (OPAT) was performed. The likelihood of developing nephrotoxicity (>= 50% increase in serum creatinine from baseline) was evaluated in relation to demographic variables, underlying co-morbidities, infectious disease diagnoses, concomitant drug exposures and vancomycin concentration. Logistic regression was used to determine the association of various variables. Classification and regression tree analysis was used to determine the most significant breakpoint for continuous variables. Results: We examined 102 adult patients between January 2004 and June 2007. The mean +/- SD age, baseline serum creatinine and steady-state vancomycin concentration were 48.2 +/- 17.6 years, 78.0 +/- 32.5 mu mol/L and 15.5 +/- 10.8 mg/L, respectively. The majority of the patients (66.7%) were treated for bone and joint infection. The cumulative incidence of nephrotoxicity was 15.7%. Nephrotoxicity was found to be associated with hypertension [odds ratio (OR) 5.302 (95% confidence interval (CI) 1.159-24.246), P = 0.031], exposure to aminoglycosides [OR 6.594 (95% CI 1.026-42.385), P = 0.047], loop diuretics [OR 8.123 (95% CI 1.449-45.528), P = 0.017], and steady-state vancomycin concentration >= 28 mg/L [OR 21.236 (95% CI 2.687-167.857), P = 0.004]. Conclusions: We have identified independent risk factors for nephrotoxicity in patients receiving continuous infusion vancomycin in OPAT. A serum steady-state vancomycin concentration >= 28 mg/L markedly increases the risk.