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.

Incidence and risk factors of vancomycin-associated acute kidney injury in a single center: Retrospective study

“…This inding is of particular importance as it suggests that the association seen between high serum vancomycin trough levels and VA-AKI is not confounded by severity of sepsis and hemodynamic instability. A recent study has also shown similar indings [3].…”

“…Vancomycin is often used as a irst line empiric therapy for many moderate-to-severe gram-positive infections and has been associated with AKI [4]. Given the widespread use of vancomycin, there are reports of VA-AKI ranging between 5% to 40% [2][3][4][5][6].…”

“…Previous reports showed that vancomycin could be both nephrotoxic and ototoxic [1]. Despite improvements in the puri ication process, literature suggests that vancomycin is still associated with 5% -40% increased incidence of acute kidney injury (AKI) [2][3][4][5][6]. A recent systematic review and meta-analysis suggested that use of vancomycin has a relative risk of 2.45 for development of AKI [7].…”

“…The exact mechanism of AKI with vancomycin use (VA-AKI) remains unclear; however, studies suggest that certain risk factors may increase the risk. Obesity [8,9] intensive care unit (ICU) stay [10] higher doses of vancomycin, prolonged duration of treatment, elevated serum vancomycin levels https://doi.org/10.29328/journal.jcn.1001067 [11] and concomitant treatment with nephrotoxic agents [12], have been implicated as risk factors which may have a role in the development of VA-AKI [2,3,10,13]. Hirai and colleagues observed that patients in their study showed poor recovery from vancomycin nephrotoxicity although vancomycin trough concentrations improved.…”

Population Pharmacokinetics of Vancomycin in Kidney Transplant Recipients: Model Building and Parameter Optimization

“…The minimum inhibitory concentration (MIC) of vancomycin for most sensitive bacteria is 0.1–2 μg ml -1 ( Bhongsatiern et al, 2015 ; Bruniera et al, 2015 ). Many of the adverse reactions of vancomycin such as bone marrow hematopoietic toxicity and nephrotoxicity are closely related to the blood concentration and area under the curve (AUC) of vancomycin ( Bruniera et al, 2015 ; Gyamlani et al, 2019 ). Pharmacokinetics, blood concentration, efficacy, and toxicity of vancomycin vary according to various factors including patient’s physiology, pathology, and combined medication ( Giuliano et al, 2010 ; Chu et al, 2016 ; Bakke et al, 2017 ; Hu et al, 2018 ).…”