Vancomycin loading dose is associated with increased early clinical response without attainment of initial target trough concentration at a steady state in patients with methicillin-resistant Staphylococcus aureus infections.

Abstract

Vancomycin therapeutic guidelines suggest a loading dose of 25-30mg/kg for seriously ill patients. However, high-quality data to guide the use of loading doses are lacking. We aimed to evaluate whether a loading dose (a) achieved a target trough concentration at steady state and (b) improved early clinical response. Patients with an estimated glomerular filtration rate ≥90mL/min/1.73m2 were included. A loading dose of 25mg/kg vancomycin followed by 15mg/kg twice daily was compared with traditional dosing. A Cmin sample was obtained before the fifth dose. An early clinical response 48-72hours after the start of therapy and clinical success at end of therapy (EOT) was evaluated in patients with methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative Staphylococci or Enterococcus faecium. There was no significant difference in Cmin between the regimen with and without a loading dose (median: 10.4 and 10.2µg/mL, P=.54). Proportions of patients achieving 10-20 and 15-20µg/mL were 56.9% and 5.6%, respectively, in patients with a loading dose. Although there was no significant difference in success rate at EOT between groups, a loading dose was associated with increased early clinical response for all infections (adjusted odds ratio [OR]: 4.588, 95% confidence interval [CI]: 1.373-15.330) and MRSA infections (OR: 12.065, 95% CI: 1.821-79.959). Study limitations included no Cmin measurements within 24hours and the inclusion of less critically ill patients. A loading dose of 25mg/kg followed by 15mg/kg twice daily did not achieve the optimal Cmin at steady state in patients with normal renal function. However, more early clinical responses were obtained with a loading dose compared with traditional dosing, possibly because of a prompt albeit temporary achievement of a more effective concentration.