Vancomycin loading dose is associated with increased early clinical responses without attainment of initial target trough concentration at a steady state in patients with normal renal function

Abstract

Background Vancomycin therapeutic guidelines suggest a loading dose of 25–30 mg/kg for seriously ill patients. However, high-quality data to guide the use of loading dose are lacking. Evaluate whether a loading dose 1) achieves a target trough concentration (Cmin) at steady state and 2) improves early clinical responses. Methods Patients with an estimated glomerular filtration rate ≥90 mL/min/1.73 m2 were included. A loading dose of 25 mg/kg vancomycin followed by 15 mg/kg twice daily was compared with traditional dosing. A Cmin sample was obtained before the fifth dose. An early clinical response 48–72 h 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. Results There was no significant difference in Cmin between the regimen with and without a loading dose (median: 10.4 µg/mL and 10.2 µg/mL, P=0.538). Proportions of patients achieving 10–20 µg/mL and 15–20 µg/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, loading dose was associated with increased early clinical responses for all infections [adjusted odds ratio (OR): 4.829, 95% confidence interval (CI): 1.441–16.188] and MRSA infections (OR: 10.851, 95% CI: 1.701–69.233). Increased adverse events were not observed with the loading dose. Study limitations included no Cmin measurements within 24 hours, and the inclusion of less critically ill patients. Conclusions Although the loading dose did not achieve optimal Cmin at steady state, a higher early clinical response was obtained compared with traditional dosing.