Vancomycin-binding characteristics in patients with serious infections.

STUDY OBJECTIVE

To examine the extent, variability, and factors affecting vancomycin protein binding.

DESIGN

Prospective, open-label, cohort study.

SETTING

A general hospital.

PATIENTS

Forty-four adults [mean (+/- SD) age 50.9 +/- 17.1 yrs, range 16.8-92.0 yrs] with serious infections.

INTERVENTIONS

Unbound (Vu) and total (Vtot) vancomycin concentrations were determined by fluorescence polarization immunoassay. A statistical analysis model used the maximum likelihood method to evaluate the association between several important variables and log Vu while controlling for log Vtot effects.

MEASUREMENTS AND MAIN RESULTS

The mean fraction percentage of unbound vancomycin was 79.5 +/- 6.0% (range 53.0-96.3%). While controlling for Vtot the total variability of Vu was 8.3%, suggesting that vancomycin binding is relatively constant in sick adults. We were able to demonstrate a significant statistical interaction effect between gender and globulin protein concentration on Vu (p = 0.022). Globulin protein concentration in men was negatively associated with Vu (p = 0.0009), but there was no association in women (p = 0.645). Age, race, peak-trough association, serum creatinine, serum albumin, serum prealbumin, and hemodialysis were not significantly associated with log Vu in the statistical model.

CONCLUSION

Compared with earlier studies in healthy adults, vancomycin binding appears to be decreased during acute illness, and intrapatient and interpatient variability are relatively small. Unbound vancomycin concentration appears to be gender dependent.