Table 1

Details of studies examining vancomycin-associated nephrotoxicitya

Study authors and type (reference)Study populationExclusionsDefinition of NTb (no., % of patients with NT)Clinical characteristics for patients with and without NTOutcomes including renal
Age (yr)ICU residenceSeverity scoreReceipt of other NTsb
Bosso et al., prospective observational study (n = 291) (21)Patients were ≥18 yr, with MRSA infections treated with VAN for ≥72 h, and had one steady-state VAN trough measurement 2–4 days into therapyPatients on concomitant AmB or NSAID, renal replacement therapy, neutropenia, or cystic fibrosisIncrease in SCR of ≥0.5 mg/dl or 50% increase from baseline for two consecutive measurements (n = 55, 19%)Not statedNT, 42%; nNT, 31%Not statedNT, 47%; nNT, 39%Not stated
Cano et al., retrospective analysis of IMPACT-HAP database (n = 188) (23)Patients had HAP, VAP, or HCAP and a baseline SCR of <2.0 mg/dl, were treated with VAN, and had at least one trough measurement takenSCR of ≥2 mg/dl on admission or history of end stage renal disease or dialysis at baselineIncrease in SCR of ≥0.5 mg/dl or 50% increase from baseline for two consecutive measurements (n = 29, 15%)NT, 60; nNT, 58All patientsAPACHE II score: NT, 20; nNT, 19NT, 55%; nNT, 29% (P < 0.01)Patients with NT had longer ICU LOS than nNT patients (17 versus 12 days, P = 0.03). Mortality and hospital LOS were similar in the two groups
Chung et al., retrospective cohort study (n = 73) (21)Patients were ≥18 yr, had nosocomial pneumonia in ICU, and were treated with VAN for ≥72 hPatients who developed AKINc within 48 h of VAN initiationAKIN classification (n = 28, 38%)Not statedAll patientsNot statedNot statedVAN failure and mortality not associated with VAN trough concentrations
Hermsen et al., retrospective cohort study (n = 55) (30)Patients were >19 yr, had MRSA infections, and were treated with VAN for ≥5 daysPatients with neutropenia and CrCl of <30 ml/minIncrease in SCR of ≥0.5 mg/dl from baseline for two consecutive measurements (n = 9, 16%)Not statedNot statedNot statedNot stated
Hidayat et al., prospective cohort study (n = 95) (13)Patients were ≥18 yr, had nosocomial MRSA infections, and were treated with VAN for ≥72 hNoneIncrease in SCR of ≥0.5 mg/dl or 50% increase from baseline for two consecutive measurements (n = 12, 19%)NT, 72; nNT, 74Not statedNot statedNT, 91%; nNT, 20% (P < 0.01)
Jeffres et al., retrospective cohort study (n = 94) (15)All patients had MRSA HCAP and were treated with VAN for ≥72 hPolymicrobial infections and acute renal failure requiring dialysisIncrease in SCR of ≥0.5 mg/dl or 50% increase from baseline for two consecutive measurements (n = 40, 43%)NT 60; nNT, 58Not statedAPACHE II: NT, 23; nNT, 18 (P < 0.01)Dependent on agent, NT, 5–63%; nNT, 5–44%SCR returned to baseline in 73% of patients prior to discharge, with no patients requiring dialysis
Kralovicova et al., retrospective cohort study (n = 198) (31)Cancer patients receiving VAN for a Gram-positive bloodstream infectionIncrease in SCR of ≥110 μmol/liter or >20% from baseline or decrease of CrCl of <0.7 ml/s (n = 50, 25%)Not statedNot statedNot stated68%Receipt of concomitant NT agents in the prior 30 days was not associated with increased NT
Kullar et al., retrospective cohort study (n = 280) (8)Adult patients with MRSA bloodstream infections, treated with VAN for ≥72 hVAN therapy <3 days and with end stage renal failureIncrease in SCR of ≥0.5 mg/dl or 50% increase from baseline for two consecutive measurements (n = 50, 19%)Not statedNot statedNot statedNot statedIncreased VAN failure (including mortality) with VAN trough concentrations of <15 mg/liter compared to trough levels of ≥15 mg/liter. LOS in hospital was longer in patients who developed NT (20 versus 13 days, P = 0.001)
Kullar et al., prospective multicenter study (n = 200) (32)Adult patients with Gram-positive infections requiring targeted VAN therapyTransplant recipient within the past 6 months; receipt of concurrent vasopressors; wt, >110 kg; baseline CrCl, <30 ml/minIncrease in SCR of ≥0.5 mg/dl or 50% increase from baseline for two consecutive measurements (n = 9, 5%)Not statedNot statedNot statedNT, 67%; nNT, 5%
Lodise et al., retrospective cohort study (n = 166) (36)Nonneutropenic (neutrophil count, ≥1,000 cells/mmd) patients, who were ≥18 yr, with a baseline SCR of <2.0 mg/dl and a Gram-positive infection, received VAN for >48 h, and had a VAN trough measurement taken within the first 96 h of therapyPatients with cystic fibrosis or who received contrast dye or vasopressors at start of VAN therapyIncrease in SCR level of 0.5 mg/dl or 50% from baseline on 2 consecutive days (n = 21, 13%)NT, 56; nNT, 56NT, 67%; nNT, 39% (P = 0.02)APACHE II score: NT, 12; nNT, 11NT, 29%; nNT, 38%The mean duration that SCR remained >50% above baseline was 7 days
McKamy et al., retrospective cohort study (n = 167) (38)Patients were between >1 week and 19 yr with age-appropriate normal baseline SCR and were treated with VAN for ≥48 h for a Gram-positive infectionPremature infantsIncrease in SCR of ≥0.5 mg/dl or 50% increase from baseline for two consecutive measurements (n = 24, 14%)Not statedNT, 92%; nNT 54% (P < 0.01)Not statedDependent on agent, NT, 8–75%; nNT, 1–24%SCR returned to baseline in 75% of patients prior to discharge, with no patients requiring dialysis
Minejima et al., prospective cohort study (n = 227) (39)Patients were >17 yr, treated with VAN for ≥5 days, and had ≥1 VAN trough measurements takenSCR of ≥2 mg/dl on admission or history of chronic kidney disease ≥stage IIIRIFLEd criteria (n = 43; 19%)NT, 68; nNT, 70NT, 29%; nNT,15% (P = 0.041)APACHE II score: NT, 9; nNT, 8NT, 22%; nNT, 10% (P = 0.017)NT was reversible in 56% of patients by the time of discharge. No patients required dialysis
Prabaker et al., retrospective cohort study (n = 348) (43)Inpatients who received VAN for ≥5 days as treatment for various infectionsSCR of ≥2 mg/dl prior to VAN therapy, NT occurring prior to 5 days, and concomitant AmB therapyIncrease in SCR level of 0.5 mg/dl or 50% from baseline on 2 consecutive days (n = 31, 9%)NT, 64; nNT, 60Not statedNot statedNT, 68%; nNT, 55%NT was reversible in 78% of patients within 72 h of VAN discontinuation. One patient required dialysis and died following withdrawal of active treatment
Wunderink et al., prospective randomized triale (n = 333) (50)Adult patients treated with VAN for MRSA nosocomial pneumoniaPatients treated with any MRSA-active antibiotic >48 h within or 72 h before the prestudy periodIncrease in SCR level of 0.5 mg/dl or 50% from baseline on 2 consecutive days (n = 50, 15%)Not statedNot statedNot statedNot stated
Zimmermann et al., retrospective cohort study (n = 45) (51)Patients were ≥18 yr, with Gram-positive bloodstream infections, were treated with VAN for ≥48 h, and had two VAN trough measurements takenAcute or chronic renal impairment, receipt of nephrotoxin vasopressorsIncrease in SCR of ≥0.5 mg/dl or 50% increase from baseline for two consecutive measurements (n = 9, 5%)NT, 58; nNT, 60NT, 25%; nNT, 5%Not statedExcludedFollowing dosage adjustment, SCR returned to baseline in all patients within 3–5 days
  • a Abbreviations: VAN, vancomycin; AmB, amphotericin B; MRSA, methicillin-resistant S. aureus; NT, nephrotoxic/nephrotoxicity; nNT, nonnephrotoxic/no nephrotoxicity; SCR, serum creatinine; CrCl, creatinine clearance; GFR, glomerular filtration rate; ICU, intensive care unit; APACHE II, acute physiology and chronic health evaluation score; SAPS, simplified acute physiology score; HAP, hospital-acquired pneumonia; HCAP, health-care associated pneumonia; VAP, ventilator-associated pneumonia; NSAID, nonsteroidal anti-inflammatory drugs; LOS, length of stay.

  • b Nephrotoxins include any or all of the following: aminoglycosides, amphotericin B, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, colistin, contrast dye, cyclosporine, cisplatin, diuretics, nonsteroidal anti-inflammatory drugs, tacrolimus, and vasopressors.

  • c AKIN, Acute Kidney Injury Network classification, which classifies acute renal injury into 1 of 3 stages: stage 1, increase in SCR of >0.3 mg/dl or a 1.5× increase from baseline; stage 2, 2× increase in SCR from baseline; stage 3, increase in SCR of ≥4 mg/dl (with an acute rise of ≥0.5 mg/dl) or 3× increase from baseline (62).

  • d RIFLE, Risk-Injury-Failure-Loss End-stage renal disease criteria, which classify acute renal injury into 5 groups: (i) risk of renal dysfunction, 1.5× increase in SCR or 25% decrease in GFR; (ii) renal injury, 2× increase in SCR or 50% decrease in GFR; (iii) failure, 3× increase in SCR or acute increase of ≥0.5 mg/dl or ≥75% in GFR; (iv) complete loss of renal function persisting for >4 weeks; and (v) end stage renal disease (63).

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