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Comparison of the Nephrotoxicity of Vancomycin in Combination with Cefepime, Meropenem, or Piperacillin / Tazobactam: A Prospective, Multicenter Study
Mullins B, Kramer C, Bartel, B, et al. Ann Pharmacother. 2018; 52: 639-644.
Study Question: Is there a difference between intravenous vancomycin in combination with cefepime, meropenem, or piperacillin/tazobactam and the incidence of acute kidney injury (AKI)?
Study Description: This multicenter observational study included adult patients receiving ≥ 72 hours of vancomycin and at least 48 hours overlap with cefepime, meropenem, or piperacillin/tazobactam (PT). Patients were excluded for a history of chronic kidney disease, baseline SCr ≥ 1.5 mg/dL, AKI during indexed hospitalization, vancomycin trough concentrations < 10 mg/L, receipt of cefepime, meropenem, or PT prior to inclusion, or receipt of more than one beta-lactam during vancomycin therapy. The primary outcome was the development of AKI (≥ 1.5-fold increase in SCr or CrCL < 30 mL/min) and associated risk factors.
Results: A total of 242 patients were included; 94 patients received vancomycin plus PT (VPT), 47 received vancomycin plus meropenem (VM), and 101 received vancomycin plus cefepime (VC). Rates of AKI were 29.8% with VPT, 5.9% with VC, and 14.9% with VM. There was a statistically higher incidence of AKI in the VPT group when compared to both VC alone (p < 0.001) and the combined VC+VM group (p < 0.001). Independent predictors of developing AKI were VPT therapy [OR 6.65 (95% CI 2.79-15.84), p < 0.001], concomitant loop diuretics [OR 3.27 (95% CI 1.42-7.53), p = 0.005], concomitant vasopressors [OR 5.04 (95% CI 1.66-15.35), p = 0.004], and a maximum vancomycin trough > 30 mg/L [OR 13.33 (95% CI 3.13-56.77), p < 0.001].
Conclusions: VPT is associated with a higher risk of developing AKI when compared to combination with VC or VM. Risk of AKI increases with the administration of vasopressors, loop diuretics, and vancomycin trough > 30 mg/L.
Perspective: This study was the first prospective, multicenter study investigating the effect of combination VPT on acute AKI. This study is consistent with retrospective comparisons, which demonstrated an increased risk of AKI with VPT compared to other combinations. Less than half of the patients in this study required ICU admission, with approximately 60% not meeting sepsis criteria. However, vasopressor use and diuretic use were predictors of AKI, which suggests VPT combinations should undergo careful consideration when treating patients in the intensive care unit where vasopressors or diuresis may be necessary.