PK/PD of vancomycin in patients with severe acute pancreatitis combined with augmented renal clearance

Abstract

To evaluate the serum trough concentration and the pharmacokinetics/pharmacodynamics (PK/PD) of vancomycin in patients with severe acute pancreatitis (SAP), and analyze the effect of vancomycin continuous infusion for optimizing the characteristics of its PK/PD. The inhospital patients with SAP received vancomycin treatment and admitted to emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2011 to December 2016 were enrolled. Steady-state trough concentrations of vancomycin from patients were collected retrospectively. The SAP patients were divided into augmented renal clearance (ARC) and non-ARC groups, as well as systemic inflammatory response syndrome (SIRS) and non-SIRS groups according to the patients with or without symptom above. Adjustments of increased dosage or 24-hour continuous infusion or increase vancomycin dose were made for patients if the steady-state trough concentrations fell below the target level. Steady state trough concentration for vancomycin intermittent infusion or steady state concentration for vancomycin continuous infusion was determined by the fluorescence polarization immunoassay method. PK parameters of vancomycin were calculated using the Bayesian estimator and the area under the serum drug concentration-time curve (AUCc-t), the minimum inhibitory concentration (MIC) and AUCc-t/MIC was recorded and calculated. The steady state trough concentration or steady state concentration from 61 patients with SAP were collected with mean steady state trough concentration of vancomycin of (7.7±4.4) mg/L, which was significantly lower than standard concentration (15 mg/L, P < 0.001). Apparent volume of distribution (Vd) and clearance of vancomycin was (1.06±0.26) L/kg and (8.9±2.8) L/h. The serum steady state trough concentration of vancomycin in ARC group (n = 33) was significantly lower than that in non-ARC group (n = 28; mg/L: 6.7±3.5 vs. 8.2±4.1, P < 0.01), clearance was significantly increased (L/h: 9.8±2.9 vs. 7.7±2.2, P < 0.01). Compared with non-SIRS group (n = 31), the serum steady state trough concentration of vancomycin in SIRS group (n = 30) was significantly lowered (mg/L: 6.1±3.2 vs. 13.0±4.2, P < 0.01), and clearance was significantly increased (L/h: 9.4±2.0 vs. 7.1±2.1, P < 0.05). Compared with the only increasing vancomycin dose group (n = 29), vancomycin continuous infusion for 24 hours (n = 21) could significantly reduce daily dosage (mg/kg: 13.6±3.9 vs. 19.1±3.5, P < 0.01), increase the serum trough concentration (mg/L: 18.1±7.0 vs. 12.6±5.3, P < 0.01), and improve the AUCc-t/MIC. The serum trough concentration of vancomycin was significantly reduced in SAP patients with ARC. The more serious of the SIRS is, the lower the vancomycin trough concentration is. Vancomycin 24-hour continuous infusion could optimize the PK/PD parameters, decrease the daily dose, increase the clinical effect, and reduce the bacterial resistance.