@article {YangP4699, author = {Wei Yang and Bei He}, title = {Population pharmacokinetics and pharmacodynamics analysis of vancomycin in patients with severe lower respiratory tract gram-positive infections}, volume = {44}, number = {Suppl 58}, elocation-id = {P4699}, year = {2014}, publisher = {European Respiratory Society}, abstract = {Objectives To develop a population pharmacokinetic (PPK) model and pharmacodynamics (PD) goal of vancomycin for the severe lower respiratory tract infection(LRTI). Methods Serum vancomycin concentrations were measured by high performance liquid chromatography. The nonlinear mixed-effects model was used to analyze the PPK model. Results 267 vancomycin concentrations data from 70 subjects were collected, including 58 men, the average age was 78 years old, APACHE II score was 16.4 and CCR was 76ml/min. 48 patients used mechanical ventilation. A two-compartment model fit the data best. The final PPK model was:CL=1.67{\texttimes}e0.35V1=33.04{\texttimes}[1-0.199{\texttimes}(60/Scr)] {\texttimes}e0.11Q=7.08{\texttimes}2.053AI{\texttimes} e0.076V2=19.29{\texttimes}e0.68(AI=1 if patients with albumin infusion; elsewise AI=0.) 42 subjects with MRSA infection were used to estimate the PD parameters. They were divided into two parts: clinical responders (n=33) and nonreponders(n=9). Logictic regression analysis revealed that Cmin/MIC significantly affected the clinical outcomes(P=0.014, OR=1.182), and ROC curve showed the cut-off value was 17.6, sensitivity and specificity were 87.9\% and 77.8\%, respectively. The 42 subjects were also divided into: bacteriology eradication (n=23) and bacteriology noneradication (n=19). Cmin/MIC affected the bacterial outcomes(P=0.03 3, OR=1.096), and the cut-off value was 16.5, sensitivity and specificity were 65.4\% and 68.7\%, respectively. Conclusions The serum creatinine and AI significant affected vancomycin PK in severe LRTI. And the cut-off value of 17.6 for Cmin/MIC can optimize vancomycin dose regimen to achieve clinical success.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/44/Suppl_58/P4699}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }