VANCOMYCIN-BINDING CHARACTERISTICS IN PATIENTS WITH SERIOUS INFECTIONS

Study Objective. To examine the extent, variability, and factors affec ting vancomycin protein binding. Design. Prospective, open-label, coho rt study. Setting. A general hospital. Patients. Forty-four adults [me an (+/- SD) age 50.9 +/- 17.1 yrs, range 16.8-92.0 yrs] with serious i nfections. Interventions. Unbound (V-u) and total (V-tot) vancomycin c oncentrations were determined by fluorescence polarization immunoassay . A statistical analysis model used the maximum likelihood method to e valuate the association between several important variables and log V- u while controlling for log V-tot effects. Measurements and Main Resul ts. The mean fraction percentage of unbound vancomycin was 79.5 +/- 6. 0% (range 53.0-96.3%). While controlling for V-tot the total variabili ty of V-u was 8.3%, suggesting that vancomycin binding is relatively c onstant in sick adults. We were able to demonstrate a significant stat istical interaction effect between gender and globulin protein concent ration on V-u (p=0.022). Globulin protein concentration in men was neg atively associated with V-u (p=0.0009), but there was no association i n women (p=0.645). Age, race, peak-trough association, serum creatinin e, serum albumin, serum prealbumin, and hemodialysis were not signific antly associated with log V-u in the statistical model. Conclusion. Co mpared with earlier studies in healthy adults, vancomycin binding appe ars to be decreased during acute illness, and intrapatient and interpa tient variability are relatively small. Unbound vancomycin concentrati on appears to be gender dependent.