Vancomycin-induced nephrotoxicity in troughs of "15-20" mg/L era: a systematic review and meta-analysis.
Antimicrob Agents Chemother. 2012 Nov 19;
Authors: van Hal SJ, Paterson DL, Lodise TP
In an effort to maximize outcomes, recent expert guidelines recommend more intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/L. The widespread use of these more intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports. The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice. All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry and Medline databases and analysed according to Cochrane guidelines. Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria. Overall, higher troughs (? 15 mg/L) were associated with increased odds of nephrotoxicity (OR 2.67; 95% CI 1.95-3.65) relative to lower troughs <15 mg/L. The relationship between trough ? 15 mg/L and nephrotoxicity persisted when the analysis was restricted to studies that only examined initial trough concentrations (OR: 3.12; 95% CI 1.81-5.37). The relationship between troughs ? 15 mg/L and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event. An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration. Vancomycin-induced nephrotoxicity was reversible in the majority of cases with short-term dialysis required only in 3% of nephrotoxic episodes. The collective literature indicates that an exposure-nephrotoxicity relationship exists for vancomycin. The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy.
PMID: 23165462 [PubMed - as supplied by publisher]