Table 2

Risk of nephrotoxicity following vancomycin exposurea

StudyIncidence of NT (no. of patients with NT/total no.)VAN trough measurementNT incidence (no. of patients with NT/total no.) with VAN trough of:Duration of VAN exposureIndependent predictors of NT on multivariate analysis (if performed)
<15 mg/liter≥15 mg/literP value
Bosso et al. (21)19% (55/288)Initial (single level taken 2–5 days into therapy). If multiple levels taken during this period, avg initial level9% (13/146)b30% (42/142)b<0.01Avg duration of VAN prior to NT was 10.6 daysVAN trough of ≥15 mg/liter (OR, 3.6; 95% CI, 1.8–7.6), black race (OR, 2.6; 95% CI, 1.3–5.2), and heart failure (OR, 3.7; 95% CI, 1.0–13.2) were independent predictors of NT. Incremental increase in rate of NT from 32 to 45 and 50% with rising VAN troughs of ≥20, ≥25, and ≥30 mg/liter, respectively
Cano et al. (22)15% (29/188)Initial (highest level in the first 4 days of VAN therapy)7% (7/99)25% (22/89)<0.01Median duration of VAN prior to NT was 8 daysVAN trough of ≥15 mg/liter (OR, 5.2; 95% CI, 1.9–13.9), duration of VAN (OR, 1.1 for each additional day; 95% CI, 1.0–1.23), and concomitant aminoglycoside use (OR, 2.7; 95% CI, 1.1–6.5) were independent predictors of NT. Incremental increase in rates of NT from 7% to 34% for rising VAN trough levels from <10 to >20 mg/liter
Chung et al. (23)38% (28/73)Initial (level taken after 3–5 doses of VAN therapy)33% (16/48)b48% (12/25)b0.21Not statedNot performed
Hermsen et al. (30)16% (9/55)Avg10% (4/39)31% (5/16)0.04Median duration of VAN prior to NT was 12 daysNot performed
Hidayat et al. (13)12% (11/95)Mean0% (0/32)17% (11/63)0.01Median duration of VAN prior to NT was 17 days. Increased NT (6, 21, and 30%) with longer durations of VAN (7, 8–14, and >14 days, respectively)Not performed. In patients not receiving concurrent nephrotoxins, VAN trough concentrations of ≥15 mg/liter remained significantly associated with NT: 2% (1/44), versus 0% (0/24) for troughs of <15 mg/liter
Jeffres et al. (15)43% (40/94)Initial (level taken immediately following the 3rd dose)29% (13/45)55% (27/49)0.01Not stated. NT was 20% and 45% for <14 and >14 days, respectively, of VANVAN trough of ≥15 mg/liter (OR, 2.82; 95% CI, 1.02–7.74) was the only independent predictor of NT
Kralovicova et al. (31)25% (50/198)Not stated21% (29/138)35% (21/60)NSNot statedNot performed
Kullar et al. (8)18% (50/280)Initial (level taken immediately before the 4th dose)16% (23/141)19% (27/139)NSNot statedNot performed
Kullar et al. (32)5% (9/200)Initial (level taken immediately before the 4th or 5th dose)1% (1/84)7% (8/116)Median duration of VAN prior to NT was 8 daysNot performed
Lodise et al. (36)13% (21/166)Initial (highest trough within the first 4 days of VAN therapy)10% (14/139)26% (7/27)<0.05Mean duration of VAN prior to NT was 6 daysVAN trough (adjusted OR, 1.1 for each unit increase in trough; 95% CI, 1.1–1.2) and residence in ICU (OR, 3.25; 95% CI, 1.2–9.0) were independent predictors of NT
McKamy et al. (38)14% (24/167)Avg7% (8/110)28% (16/57)<0.01Mean durations of VAN prior to NT were 4.3 and 6.7 days for patients with troughs of <15 and ≥15 mg/liter, respectivelyVAN trough of ≥15 mg/liter (OR, 3.3; 95% CI, 1.2–9.0) and receipt of furosemide in ICU (OR, 9.5; 95% CI, 3.4–26) were independent predictors of NT
Minejima et al. (39)19% (43/227)Avg16% (25/155)24% (17/72)0.27Mean duration of VAN prior to NT was 9 days. NT, 13% and 25% for ≤7 and >7 days, respectively, of VANVAN trough of ≥15 mg/liter was not an independent predictor of NT (OR, 1.1, 95%; CI, 0.5–2.5), while malignancy (OR, 2.8; 95% CI, 1.2–6.3), residence in ICU (OR, 2.5; 95% CI, 1.2–5.4), and previous AKI were (OR, 6.3; 95% CI, 1.6–24.6)
Prabaker et al. (43)9% (31/348)Mean8% (24/294)13% (7/54)0.11Median duration of VAN prior to NT was 7 daysVAN trough of ≥15 mg/liter (OR, 2.1; 95% CI, 0.9–4.6) was not an independent predictor of NT, while receipt of intravenous contrast dye was (OR, 3.6; 95% CI, 1.5–8.7)
Wunderink et al. (50)15% (50/333)Median11% (24/215)c22% (26/118)cNot statedNot performed
Zimmermann et al. (51)18% (8/45)Initial (first level obtained after the 4th dose)0% (0/33)67% (8/12)Avg duration of VAN prior to NT was 8.1 daysNot performed
  • a Abbreviations: VAN, vancomycin; NT, nephrotoxic/nephrotoxicity; nNT, non-nephrotoxic/nephrotoxicity; AKI, acute kidney injury.

  • b Represents the subset of original patients that had vancomycin trough data recorded.

  • c These data, obtained from the Zephyr study (vancomycin versus linezolid for MRSA nosocomial pneumonia) and supplied by Pfizer, represent the intention to treat the vancomycin-treated arm in cases where vancomycin trough data were measured or available (50).