High dose vancomycin for osteomyelitis: continuous vs. intermittent infusion

Objectives: To compare the efficacy, ease of use and safety of intermittent vancomycin infusion (IVI) and continuous vancomycin infusion (CVI) in high-dose therapy of osteomyelitis. Methods: Forty-four patients with an osteomyelitis requiring vancomycin for more than 4 weeks were prospectively included, 21 receiving IVI and 23, CVI. The target serum concentration of vancomycin was 20-25 mg/L. Pharmacokinetics, adverse effects, and clinical efficacy were recorded. Results: The mean daily vancomycin dosing was the same in the two groups, but the serum vancomycin concentrations (trough or plateau) were lower in the IVI group than the CVI group (21(.)7 +/- 9(.)3 and 26(.)0 +/- 6(.)1 mg/L, respectively; P < 0(.)0001). The target concentrations were achieved quicker with CVI, and daily dosing was changed more frequently in the IVI group. After reaching the target, variability of vancomycin serum concentration (trough or plateau concentrations) was higher in the IVI group than in CVI group (standard deviation 7-9 mg/L vs. 5(.)6 mg/L, respectively; P = 0(.)001). CVI did not show clinical superiority, but adverse drug effects were more frequent in the IVI group as compared with the CVI group, 9 (42(.)9%) and 2 (8(.)7%), respectively (P = 0(.)03). Survival multiple regression using Cox's proportional hazard model showed that IVI (RR = 5(.)9, P = 0(.)03) and osteomyelitis of the foot (RR = 5(.)2, P = 0(.)01) were the only factors associated with adverse drug reactions leading to treatment termination. Conclusions: CVI is practical and effective, and may be a good alternative for patients requiring prolonged treatment with high vancomycin serum levels.