Reduced vancomycin clearance despite unchanged creatinine clearance in patients treated with vancomycin for longer than 4 weeks.

Creatinine clearance-based nomograms are used routinely during the early phase of vancomycin therapy for individualizing doses. The authors studied whether such nomograms are also valid for patients receiving the drug for an extended period of longer than 4 weeks. A retrospective analysis was conducted on the therapeutic drug monitoring data obtained from 85 patients who received an intermittent intravenous infusion of vancomycin. The patients were allocated to one of five groups according to the length of drug exposure: Group 1 (4-7 days; n = 31), Group 2 (8-14 days; n = 22), Group 3 (15-21 days; n = 13), Group 4 (22-28 days; n = 8), and Group 5 (longer than 29 days; n = 11). Systemic clearance of vancomycin and estimated creatinine clearance calculated by Cockcroft & Gault's formula obtained from Groups 2 through 5 were compared with those from Group 1. Patients who had received vancomycin for longer than 4 weeks (Group 5) showed a significant (P < 0.05) reduction in systemic clearance of vancomycin by 50% compared with Group 1, whereas creatinine clearance remained unchanged. This study demonstrated that prolonged administration of vancomycin for over 4 weeks may result in a more pronounced reduction in systematic clearance of vancomycin than creatinine clearance. Our data suggest that creatinine clearance-based nomograms for individualizing vancomycin doses should be used with caution in patients who require substantially prolonged drug exposure such as those with infective endocarditis.