Correlation of Initial Dose Option With Plasma Vancomycin Exposure and Safety in Older Chinese Patients: a Cohort Retrospective Study

Abstract Background: The option of initial vancomycin dose for older patients is still controversy.Methods: Vancomycin trough concentrations in older patients who received vancomycin initial dose of ≥1.5g/day or dosing recommended by package insert (≤1g/day) were compared. The relationship between independent covariate variables and trough concentration were identified, and changes in renal function and vancomycin-related nephrotoxicity was evaluated.Results: About 187 vancomycin trough samples were obtained from 97 older patients (56.7% males, median age of 70 (IQR=8) years). Significant difference was observed in vancomycin trough concentration between the two groups (17.22±7.52 vs. 13.78±6.90 mg/L; p=0.037). The proportion of VCM trough concentration within the therapeutic target concentration was 55% in group A and 48% in group B. Subsequent dose adjustment should be taken in 54 (65.9 %) patients in group A and 9 (60%) patients in group B to reach the target trough levels. SCr after medication, baseline eGFR, eGFR after medication and death had a significant effect on VCM trough concentrations in group A. The incidence of AKI was 8.5% in group A and 20.0% in group B, logistic regression model showed positive correlation between vancomycin trough level and the incidence of AKI. Conclusion: Compared with the recommended dose by package insert, the daily dosing recommendation of ≥1.5g/d for older patients result in a higher incidence of target trough concentration. Yet, the incidence of nephrotoxicity has not increase significantly. Prospective studies with large sample size are needed to define the optimal vancomycin dose in older patients.