Evaluation of efficacy and nephrotoxicity during vancomycin therapy: A retrospective study in China

Abstract

The aim of the present study was to investigate the predictive value of vancomycin serum concentrations regarding its efficacy and nephrotoxicity in a Chinese population and to determine a relatively safe optimal target concentration during vancomycin therapy. A total of 65 patients that received vancomycin between March 2013 and March 2018 at Shanghai 10th People's Hospital (Shanghai, China) were enrolled and their vancomycin trough and peak concentrations were monitored. Factor analysis was performed in order to exclude interaction between variables. Univariate and multivariate analyses were used to identify predictors of drug efficacy and nephrotoxicity. Receiver operating characteristic curve analysis was performed to determine the thresholds of the vancomycin trough and peak concentrations for optimal efficacy and acceptable nephrotoxicity, respectively. Among the 65 cases, treatment was deemed to be effective for 43 patients and ineffective for 22 patients. Furthermore, 20 patients fulfilled the criteria for nephrotoxicity. A total of 15 continuous variables loaded the first five factors by factor analysis (which converts large numbers of highly inter-correlated variables into a small number of comprehensive indicators that reflect a dimensionality reduction) and the factors were as follows: Inflammation, renal function, liver function, vancomycin trough and peak concentrations, and nutritional status. Univariate and multivariate analyses identified the trough concentration and peak concentration as independent variables associated with efficacy and nephrotoxicity of vancomycin, and the nutritional status was a risk factor associated with efficacy. Regarding efficacy, the critical values for the trough concentration and peak concentration were determined to be 9.02 mg/l (95.3% sensitivity and 68.2% specificity) and 23.62 mg/l (83.7% sensitivity and 59.1% specificity), respectively. The thresholds of vancomycin trough and peak concentrations for the development of nephrotoxicity were 16.08 mg/l (80.0% sensitivity and 84.4% specificity) and 30.42 mg/l (75.0% sensitivity and 73.3% specificity), respectively. In conclusion, during vancomycin therapy, the trough and peak concentrations are associated with efficacy and nephrotoxicity. Furthermore, a trough concentration between 9.02 and 16.08 mg/l and a peak concentration of 23.62-30.42 mg/l were determined to be relatively safe (the clinical trial registry no. ChiCTR-OPC-16007920).

Risk factors for vancomycin‐associated acute kidney injury: A systematic review and meta‐analysis

“…Among these, 261 studies were excluded for the following reasons: evaluating antibiotics other than vancomycin ( n = 104), evaluating outcomes other than AKI ( n = 45), not assessing risk factors ( n = 68), not original articles ( n = 4), involving paediatric patients ( n = 8), involving nonhuman subjects ( n = 12), overlapping study population ( n = 3), not a patient‐level analysis ( n = 1), involving patients who underwent renal replacement therapy ( n = 4), and data extraction not possible or feasible ( n = 12). Finally, 53 studies were included in the meta‐analysis 6–8,10–12,21–67 . A flow diagram summarizing the study selection process is shown in Figure 1.…”

Therapeutic Drug Monitoring of Antibiotics: Defining the Therapeutic Range

“…111,112 An AUC 0–24 /MIC ratio of ≥400 is recommended for improved clinical response against S. aureus infection, 29,94,103,107,109,112,150–152 whereas higher exposures are probably required when treating critically ill patients with septic shock. 29 Prolonged (≥7 days) and high vancomycin exposure, especially C min concentrations of >15 mg/L 96,98,102,153,154 or AUC 0–24 exposures of >600, 95–97 is commonly associated with nephrotoxicity. Alternative indices, including AUC 0–48 142 and AUC 24–48 , 28,108,155 have also been suggested to monitor the efficacy and toxicity of vancomycin.…”

“…critically ill patients with septic shock. 29 Prolonged ($7 days) and high vancomycin exposure, especially C min concentrations of .15 mg/L 96,98,102,153,154 or AUC 0-24 exposures of .600, [95][96][97] is commonly associated with nephrotoxicity. Alternative indices, including AUC 0-48 142 and AUC 24-48 , 28,108,155 have also been suggested to monitor the efficacy and toxicity of vancomycin.…”

Analytical validation of a quantitative method for therapeutic drug monitoring on the Alinity®c Abbott

“…Therapeutic drug monitoring of aminoglycosides is essential because of their potential ototoxicity and nephrotoxicity [5]. Vancomycin is an antibiotic also used for the treatment of serious infections which can cause serious life-threatening side effects [6]. Theophylline is a bronchodilator used to treat asthma symptoms for which overdose can occur rapidly [7].…”