Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections

Abstract

Ten patients were treated with conventional dosing (CD) and continuous-infusion (CI) vancomycin therapy in this prospective, randomized, crossover study. Patients were randomized to receive either CD or CI therapy for 2 consecutive days and then crossed over to receive the opposite regimen for 2 days. CD therapy consisted of 1 g of vancomycin every 12 h. CI therapy consisted of a 500-mg loading dose followed by 2 g infused over 24 h. Ten serum samples were obtained on the second day of each therapy for pharmacokinetic and pharmacodynamic analyses. Two clinical isolates of Staphylococcus aureus, one methicillin sensitive (MSSA 1199) and one methicillin resistant (MRSA 494), were chosen for pharmacodynamic evaluation of both regimens. The patient demographics (means +/- standard deviations [SD]) were as follows: sex, six males, four females; age, 36 +/- 11 years; and serum creatinine, 0.72 +/- 0.18 mg/dl. Mean pharmacokinetic parameters +/- SD for CD therapy were as follows: elimination rate constant, 0.16 +/- 0.07 h-1; half-life, 5.6 +/- 3.5 h; volume of distribution, 33.7 +/- 25 liters, 0.5 +/- 0.2 liters/kg; maximum concentration in serum, 53.4 +/- 19.3 micrograms/ml; and minimum concentration, 8.4 +/- 5.9 micrograms/ml. The steady-state concentration for CI was 20.2 +/- 11.1 micrograms/ml. Overall, both regimens resulted in the MIC being exceeded 100% of the time. The mean CD trough serum bactericidal titer (SBT) was 1:8, and the average CI SBTs were 1:16 for both isolates. Even though there was no statistically significant difference between CD trough and CI SBTs, the CI SBTs remained > 1:8 for 100% of the time versus 60% of the time for CD therapy. During CI therapy, 20 and 40% of the patients maintained SBTs of > 1:32 throughout the dosing interval for MSSA 1199 and MRSA 494, respectively. During CD therapy, however, only 10% of patients maintained SBTs of > 1:32 during the entire dosing interval for both isolates. The mean areas under the bactericidal titer-time curve (AUBC24s) +/- SD for MSSA 1199 were 528 +/- 263 for CD therapy and 547 +/- 390 for CI therapy. The mean AUBC24s +/- SD against MRSA 494 were 531 +/- 247 for CD and 548 +/- 293 for CI therapy. Similar to the AUBC24, the mean area under the concentration-time curve for a 24-h dosing interval divided by the MIC (AUC/MIC24) ratios +/- SD were 550.0 +/- 265.7 for CD and 552.6 +/- 373.4 for CI therapy, respectively. No statistically significant differences were found between any of the pharmacodynamic parameters for CD and CI therapy. In addition, no adverse effects with either CD or CI therapy were observed during the study. We conclude that CI and CD vancomycin therapy demonstrated equivalent pharmacodynamic activities. Although CI therapy was more likely to result in SBTs that remained above 1:8 for the entire regimen, the clinical impact of this result is unknown. Serum drug concentration variability was observed with both treatment regimens but to a lesser extent with CI administration. CI administration of vancomycin should be further evaluated to determine the clinical utility of this method of administration.

Nephrotoxicity of continuous versus intermittent infusion of vancomycin in outpatient parenteral antimicrobial therapy

“…By optimising the pharmacokinetics and pharmacodynamics of vancomycin, it may be possible to maximise therapeutic concentrations whilst minimising the risk of drug toxicity, as in the experience of aminoglycosides [7,8]. Compared with intermittent infusion (II), continuous infusion (CI) of vancomycin is cheaper [9] and logistically more convenient, achieves target vancomycin concentrations faster [9,10], results in less variability in serum vancomycin concentrations [9][10][11], requires less therapeutic drug monitoring [9] and achieves higher vancomycin concentrations in pleural fluid [12]. Although clinical and microbiological outcomes for CI and II of vancomycin were equivalent [9,10], adverse drug effects were significantly reduced in CI of vancomycin [10].…”

Loading dose of vancomycin in critically ill patients: 15mg/kg is a better choice than 500mg

“…of vancomycin has been proposed and investigated in various clinical situations. Early uncontrolled and recent prospective studies have demonstrated similar clinical outcome of continuous infusion compared with intermittent dosing, with less variability in blood concentration [3], a sustained drug level in pleural fluid [4], faster acquisition of target concentration and a reduction in the costs of vancomycin administration by 23% [5]. Current literature emphasised the need for maintaining a plateau vancomycin concentration in serum of 20 mg/L according to available data on the MIC of vancomycin against staphylococcus species, its protein binding and its diffusion into tissues [5].…”

“…All rights reserved. doi:10.1016/j.ijantimicag.2005.11.009 over 30 min [3,4] to 15 mg/kg infused over 60 min [5] to 120 min [7]. The present prospective study was designed to compare two different loading doses of vancomycin for suspected Gram-positive infections: 500 mg versus 15 mg/kg.…”

Therapy of ventilator-associated pneumonia

“…Our protocol is based on giving 15 mg/kg vancomycin over 1 h followed by 30 mg/kg infused over 24 h by volumetric infusion pump. The dose is adjusted to maintain a plateau serum vancomycin concentration between 20 and 30 mg/l [25,26].…”

“…Conventional dosing and continuous-infusion vancomycin therapy may have similar outcomes in patients with bloodstream infections [26]; however, vancomycin should not be considered as a first-line therapy for Gram-positive lung infection in critically ill patients. Optimal therapy with vancomycin depends on maintaining a concentration above that needed for antibacterial activity and is therefore determined by the trough concentration.…”