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October 1, 2019
Vancomycin Area Under the Concentration-Time Curve Threshold Associated with Nephrotoxicity: Vancomycin remains a mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) infection. Because of the high mortality rate associated with MRSA infections, clinicians target higher vancomycin trough concentrations (15-20 mg/L) to attain the optimal efficacy target of area under the curve to minimum inhibitory concentration ratio (AUC/MIC) ≥ 400. However, a vancomycin trough concentration >15 mg/L increases the risk of nephrotoxicity. AUC has been identified as a better predictor of vancomycin-induced nephrotoxicity. Recent studies analyzed the relationship between vancomycin AUCs and risk of nephrotoxicity using the Bayesian method. An AUC <650 mg*h/L is suggested as an acceptable threshold of vancomycin nephrotoxicity in both adults and pediatric patients. Proposed vancomycin dosing guidelines recommend AUC/MIC of 400-600 assuming a vancomycin MIC of ≤1 mg/L as new pharmacokinetic-pharmacodynamic (PK/PD) target for maximal efficacy and minimal nephrotoxicity in patients with MRSA infections. AUC-guided vancomycin dosing may need the utilization of Bayesian software programs.
Upon completion of the chapter, the reader will be able to:
Assess a patient’s kidney function based on clinical presentation, laboratory results, and urinary indices.
Identify pharmacotherapeutic outcomes and endpoints of therapy in a patient with acute kidney injury (AKI).
Apply knowledge of the pathophysiology of AKI to development of a treatment plan.
Develop strategies to minimize the occurrence of drug- and radiocontrast-induced AKI.
Monitor and evaluate the safety and efficacy of the therapeutic plan.
Acute kidney injury (AKI) is a potentially life-threatening syndrome that occurs primarily in hospitalized patients and frequently complicates the course of those who are critically ill. It is characterized by a rapid decrease in glomerular filtration rate (GFR) and the resultant accumulation of nitrogenous waste products (eg, creatinine), with or without a decrease in urine output.
The term acute kidney injury has replaced the name acute renal failure because it more completely encompasses the entire spectrum of acute injury to the kidney, from mild changes in kidney function to end-stage kidney disease requiring renal replacement therapy (RRT).
AKI is defined as an increase in serum creatinine (SCr) of at least 0.3 mg/dL (27 μmol/L) within 48 hours, a 50% increase in baseline serum creatinine within 7 days, or a urine output of less than 0.5 mL/kg/h for at least 6 hours. Only one criterion needs to be met for diagnosis of AKI.1
EPIDEMIOLOGY AND ETIOLOGY
Approximately 7% to 18% of all hospitalized patients develop AKI.2 More than half of those who are critically ill develop AKI,3 and 30% to 40% of survivors of AKI develop chronic kidney disease (CKD).3 Despite improvements in the medical care of individuals with AKI, mortality remains high. About 4% ...