Xiaowu Zhang1, Donghao Wang2. 1. Department of Intensive Care Unit, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China. Electronic address: zxwtjmuch@163.com. 2. Department of Intensive Care Unit, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
Abstract
OBJECTIVE: This study was designed to investigate the characteristics and impact indicator of vancomycin pharmacokinetics in cancer patients complicated with severe pneumonia. METHODS: Fifty-seven cancer patients complicated with severe pneumonia were included in this research. Vancomycin serum trough concentrations were measured using the fluorescence polarization immunoassay (FPIA) method. The Bayesian estimator was used to calculate the pharmacokinetic parameters. RESULTS: The average initial therapeutic dose of vancomycin was 15.18 ± 3.29 mg/kg (q12 h). Our study shows that vancomycin initial trough concentrations measured in cancer patients are significantly reduced (6.54 ± 3.11 mg/L; p < 0.0001) compared with the recommended standard vancomycin trough concentration (10-15 or 15-20 mg/L). Meanwhile, the clearance (CL) and volume of distribution (Vd) of vancomycin was increased significantly in cancer patients. Multivariate linear regression analysis revealed that Cys-C was the most important variable for vancomycin trough concentration (r2 = 0.439). The relationships between vancomycin trough concentrations and Cys-C were further evaluated after the 57 patients were grouped by cut-off point (1.44 mg/L) of the serum Cys- C levels before vancomycin was administered. Compared with group Early group (Cys-C>1.44 mg/L), Delayed group (Cys-C≤1.44 mg/L) had much lower trough concentrations. Meanwhile, CL and CLcr were significantly increased in Delayed group (Cys-C≤1.44 mg/L). Although the clinical outcomes were similar between two groups, the duration of vasoactive agent in Early group was considerably shorter compared with Delayed group (χ2 = 4.213; p < 0.05). CONCLUSIONS: The serum trough concentration of vancomycin was significantly reduced in cancer patients complicated with severe pneumonia. Higher dosage regimen is needed to ensure clinical effectiveness. The Cys-C level measured prior to administration of vancomycin is suggested to be the most suitable parameter to predict whether vancomycin trough concentration is up to standard dosage. Especially for patients with baseline Cys-c less than 1.44 mg/L, it is more likely to need higher dosage algorithm.
OBJECTIVE: This study was designed to investigate the characteristics and impact indicator of vancomycin pharmacokinetics in cancerpatients complicated with severe pneumonia. METHODS: Fifty-seven cancerpatients complicated with severe pneumonia were included in this research. Vancomycin serum trough concentrations were measured using the fluorescence polarization immunoassay (FPIA) method. The Bayesian estimator was used to calculate the pharmacokinetic parameters. RESULTS: The average initial therapeutic dose of vancomycin was 15.18 ± 3.29 mg/kg (q12 h). Our study shows that vancomycin initial trough concentrations measured in cancerpatients are significantly reduced (6.54 ± 3.11 mg/L; p < 0.0001) compared with the recommended standard vancomycin trough concentration (10-15 or 15-20 mg/L). Meanwhile, the clearance (CL) and volume of distribution (Vd) of vancomycin was increased significantly in cancerpatients. Multivariate linear regression analysis revealed that Cys-C was the most important variable for vancomycin trough concentration (r2 = 0.439). The relationships between vancomycin trough concentrations and Cys-C were further evaluated after the 57 patients were grouped by cut-off point (1.44 mg/L) of the serum Cys- C levels before vancomycin was administered. Compared with group Early group (Cys-C>1.44 mg/L), Delayed group (Cys-C≤1.44 mg/L) had much lower trough concentrations. Meanwhile, CL and CLcr were significantly increased in Delayed group (Cys-C≤1.44 mg/L). Although the clinical outcomes were similar between two groups, the duration of vasoactive agent in Early group was considerably shorter compared with Delayed group (χ2 = 4.213; p < 0.05). CONCLUSIONS: The serum trough concentration of vancomycin was significantly reduced in cancerpatients complicated with severe pneumonia. Higher dosage regimen is needed to ensure clinical effectiveness. The Cys-C level measured prior to administration of vancomycin is suggested to be the most suitable parameter to predict whether vancomycin trough concentration is up to standard dosage. Especially for patients with baseline Cys-c less than 1.44 mg/L, it is more likely to need higher dosage algorithm.