Continuous infusion of vancomycin: Effective, efficient and safe

Aims: Vancomycin is an antibiotic which is used in (suspected or proven) bacteriaemia, peritonitis or osteomyelitis with grampositive micro-organisms. Currently in most Dutch hospitals vancomycin is administered as an intermittent infusion. As the killing of vancomycin is dependent of the AUC/MIC ratio and/or time above MIC, a continuous infusion should be at least as effective as an intermittent infusion based on its pharmacodynamics. Studies comparing continuous (CIV) and intermittent (IIV) infusion of vancomycin indicate continuous infusion is as effective and safe as intermittent infusion. In osteomyelitis it might even be superior. However, no loading and maintenance dosages are known for CIV. Here, we tried to establish and validate a dosing schedule for continuous infusion of vancomycin. Methods: Continuous infusion of vancomycin in patients with a calculated creatinine clearance ranging from 25 to 125 mL/min was simulated in MWharm (versie 3.60, Medi\Ware). A population model was used to calculate loading and maintenance dosages within a range of calculated creatinine clearances. The target range for steady state concentration (Css) at 24 - 48 h was set at 16 - 20 mg/L corresponding with an AUC24/MIC ratio of at least 400 mg∗h/L. A set of 20 steady state concentrations (Css's) was used to validate the proposed infusion schedule. Results: An infusion schedule for CIV was established (Table 1). Samples for validation were drawn 24 - 48 h after start of infusion. Samples were analysed by immunoassay (TDx, Abbott). Validation showed that 16 out of 20 Css's (80 %) were within the predefined target range (16 - 20 mg/L). Two patients had a Css higher than the upper limit (21.9 and 20.5) and Css's in two patients were low (11.3 and 14.4 mg/L). After dosage correction based on linear pharmacokinetics Css's at 72 h of these patients fell within the target range. Conclusion: CIV offers clear advantages over IIV for patients with a very high clearance of vancomycin and for out-of-hospital patients. Furthermore, continuous infusion is less expensive, simplifies TDM and may shorten hospital length of stay in selected patient populations. A simple and validated infusion schedule for continuous infusion is available. Table 1: Dosing schedule for continuous infusion of vancomycin. Start with loading dose: 1000 mg administered over 2 h Maintenance Dose Creat Cl∗(ml/min/1,73m2) Dose# (mg/24 h) <30 500 30 - 39 750 40 - 49 1000 50 - 59 1250 60 - 79 1500 80 - 89 1750 > 90 2000∗estimated creatinine clearance #Target Css: 16 - 20 mg/L (sample drawn 24 - 48 h after start of infusion).