Background High vancomycin trough concentrations have been correlated with good anti-MRSA and other Gram-positive activity. However, nephrotoxicity rates vary among the different studies and optimal dosage regimens remain controversial.
Purpose To compare the incidence of vancomycin-related nephrotoxicity in patients with high (>15 mg/L) vs. low (<15 mg/L) trough concentrations.
Materials and methods Retrospective study (January 2009 – August 2013). Inclusion criteria: patients older than 18 years who had completed a course of vancomycin (duration ≥ 72 h), and had at least one steady-state (after 2 to 4 days of treatment) vancomycin trough concentration determined. According to their trough levels, the patients were included into one of the following categories: vancomycin trough <15 mg/L (hereafter group 1) and those with vancomycin trough ≥15 mg/L (hereafter group 2). Pharmacokinetic data were estimated using a Bayesian approach (Abbott Base PKS). Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dL or a >50% increase from the baseline for two consecutive determinations.
Results 30 patients included, 18 belonging to group 1 and 12 to group 2. Demographics: mean age 68.1, female 33%. Median (CI95%) pharmacokinetic data for groups 1 and 2 were: AUC = 446 [394–498] and 730 [(667–794], clearance = 3.9 L/h [3.3–4.5] and 2.3 L/h [2.0–2.7], dose = 1.806.mg [1.504–2.107] and 1.847.mg [1.680–2.015], and duration of treatment 11.6 days [9.3–13.9] and 16.5 days [13.9–19.1] respectively.
Nephrotoxicity rates in group 1 and 2 were 0 and 16% respectively. Treatment with concomitant nephrotoxic drugs was not related to vancomycin nephrotoxicity: none of the 5 patients treated simultaneously with aminoglycosides developed nephrotoxicity, all of them with vancomycin trough concentrations >15 mg/L.
Conclusions The incidence of nephrotoxicity was relatively low in patients with trough concentrations above 15 mg/L. A vancomycin dosage regimen aimed to maintain trough concentrations over 15 mg/L did not compromise renal function in our cohort. In addition, the episodes recorded were moderate in severity and reversible after vancomycin discontinuation. Nonetheless, a larger population would be necessary to address these and other safety issues.
No conflict of interest.
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