Vancomycin-Associated Acute Kidney Injury in a Large Veteran Population

Abstract

Background: To determine the association of vancomycin with acute kidney injury (AKI) in relation to its serum concentration value and to examine the risk of AKI in patients treated with vancomycin when compared with a matched cohort of patients receiving non-glycopeptide antibiotics (linezolid/daptomycin).

Methods: From a cohort of > 3 million US veterans with baseline estimated glomerular filtration rate ≥60 mL/min/1.73 m2, we identified 33,527 patients who received either intravenous vancomycin (n = 22,057) or non-glycopeptide antibiotics (linezolid/daptomycin, n = 11,470). We examined the association of the serum trough vancomycin level recorded within the first 48 h of administration with subsequent AKI in all patients treated with vancomycin and association of vancomycin vs. non-glycopeptide antibiotics use with the risk of incident AKI.

Results: The overall multivariable adjusted ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptides were 1.1 (1.1-1.2), 1.2 (1-1.4), and 1.4 (1.1-1.7), respectively. When examined in strata divided by vancomycin trough level, the odds of AKI were similar or lower in patients receiving vancomycin compared to non-glycopeptide antibiotics as long as serum vancomycin levels were ≤20 mg/L. However, in patients with serum vancomycin levels > 20 mg/L, the ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptide antibiotics were 1.5 (1.4-1.7), 1.9 (1.5-2.3), and 2.7 (2-3.5), respectively.

Conclusions: Vancomycin use is associated with a higher risk of AKI when serum levels exceed > 20 mg/L.

Keywords: Outcomes; Acute kidney injury; Daptomycon; Linezolid; Vancomycin.

Figure 1:

Flow chart of patient selection.

Figure 2:

Association of maximum trough serum vancomycin levels with risk of incident AKI in adjusted and unadjusted logistic regression models in 22,057 US veteran patients. Model 1: unadjusted; model 2: demographic characteristics; model 3: model 2 variables plus comorbidities; model 4: model 3 variables plus medications, systolic/diastolic blood pressure and body mass index (BMI); model 5: model 4 variables and SOFA score components (platelet count, bilirubin and vasopressor/ionotropic medications, with and without the addition of arterial pO2; model 5 – pO2 and + pO2).

Figure 3:

Odds ratios of various stages of AKI (vs. no AKI) associated with vancomycin vs. non-glycopeptide use, in propensity score-matched patients overall and in groups categorized by maximum trough serum vancomycin level.

Figure 4:

Association of maximum trough serum vancomycin levels with risk of incident AKI in multivariable adjusted Cox regression models in patients with different doses (< 4gms/day vs ≥ 4gms/day), duration (< 7 days vs ≥ 7 days), and number of antibiotics. Models were adjusted for patient demographics, body mass index (BMI), comorbidities, baseline eGFR, mean arterial pressure, and nephrotoxic medication exposure. Patients divided into 4 groups based on the highest recorded serum vancomycin trough level 1: < 10mg/L, 2: 10-15 mg/L, 3: 15.1-20 mg/L and 4: >20mg/L