Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study

Abstract

A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 +/- 31 versus 51 +/- 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 +/- 2.2 versus 11.8 +/- 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC(24h)) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg(2)/liter(2)/h(2) [P = 0.026] and 414 versus 818 g(2) [P = 0.057], respectively). The 10-day treatment cost per patient was $454 +/- 137 in the IIV group and was 23% lower in the CIV group ($321 +/- 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.

FIG. 1

Patient selection scheme.

FIG. 2

Changes in serum creatinine concentration during treatment with vancomycin (VAN) alone or with vancomycin given concomitantly with an aminoglycoside (AGS) or with any kind of antibiotic (AB). In the whole group (n = 96), vancomycin with any kind of antibiotic was associated with a significant (P = 0.02) increase in serum creatinine concentration but this was not the case when vancomycin was given alone. No interaction with treatment groups was found, suggesting that the infusion mode had no significant role in the observed effect. The total treatment duration was 14 ± 6 days in the IIV group and 13 ± 5 days in the CIV group.

FIG. 3

Changes in serum vancomycin concentrations over time in the two treatment groups. The AUC_24h was 577 ± 120 in the CIV group and 653 ± 232 mg/liter/h in the IIV group. The AUC_24h and the daily dose given over 10 days of treatment have less variability between patients with CIV than with IIV (variance, 14,621 versus 53,975 mg²/liter²/h² [P = 0.02] and 414 versus 818 g² [P = 0.05], respectively).

FIG. 4

Time required to reach target serum vancomycin concentrations (trough concentrations in the IIV group and plateau concentration in the CIV group). With IIV, the time required to reach concentrations above 10 or 15 mg/liter was significantly longer than with CIV (∗, P < 0.05).