Pharmacokinetic Assessment of Vancomycin Loading Dose in Critically Ill Patients

Abstract

The vancomycin loading dose (LD) of 25 to 30 mg/kg is a frequently practiced strategy to achieve effective concentrations from the first-treatment dose. However, considering only the body weight for dosing might be inadequate in critically ill patients due to pharmacokinetics changes. We sought to assess achieving optimal trough serum levels of vancomycin and AUC 0 -24 /MIC in the first 24 h of treatment by using an LD based on population pharmacokinetic parameters of critically ill patients. We performed a concurrent cohort study over 22 months of patients with severe sepsis who received intravenous vancomycin. The patients were treated with three different strategies to initiate vancomycin: without an LD (group A), with an LD of 25 to 30 mg/kg (group B), and with an LD based on population pharmacokinetic parameters of the critically ill patient (group C). An optimal trough serum concentration was achieved in 5, 9, and 83% of patients in groups A, B, and C, respectively. The number of patients that reached optimal AUC 0 -24 was 2 of 18 (11%), 5 of 11 (46%), and 11 of 12 (92%) in groups A, B, and C, respectively. The statistical analysis for both parameters revealed significant differences in group C with respect to other groups. The administration of the LD calculated from population pharmacokinetic parameters from the beginning of therapy is a more efficient strategy to obtain adequate trough serum concentrations and AUC 0 -24 /MIC in critical patients.

Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants

“…Our results showed that the current daily dose was too low for all neonatal age groups but particularly for neonates <29 weeks, as less than 30% of neonates reached the steady-state target. As a loading dose strategy is recommended in adult settings in order to reduce the time needed to reach the target AUC0-24 47,48 simulations were then performed with a loading dose and optimal maintenance doses in all age groups, based on weight and PMA. Increasing the maintenance dose to 15 mg/kg 'q12h' instead of 'q24h' was also tested in the group <29 PMA weeks to optimise dosage.…”

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

“…To maintain a high concentration thereafter, an increase in the maintenance dose from 15 mg/kg to 20 mg/kg might be required [22]. Many studies reported a higher achievement of a C min >15 μg/mL after the first dose in patients with a loading dose compared with patients without a loading dose [10,15,23,24]. Casapao et al [25] evaluated the association between the day 1 vancomycin exposure profile and outcomes among patients with MRSA infective endocarditis, and an AUC/MIC of < 600 was independently associated with failure.…”

“…Clinicians, however, tend to be reluctant to use a loading dose, especially in patients with decreased renal function, for fear of causing renal injury. Alvarez et al [10] demonstrated that all patients with a loading dose who presented with decreased vancomycin clearance before the administration of vancomycin had an elevated serum concentration (>28 μg/mL) in the first 24 h of treatment. These patients, however, did not have nephrotoxicity.…”

“…In a randomized trial for the treatment of nosocomial pneumonia caused by MRSA, the median C min on day 3 was 12.3 μg/mL, and 25% of patients had a C min < 7.9 μg/mL [9]. The standard dosing regimen was inadequate at achieving the target C min [10]. In patients with sepsis, fluid extravasation causes an increase in interstitial volume.…”

Yunnan Baiyao reduces hospital-acquired pressure ulcers via suppressing virulence gene expression and biofilm formation of Staphylococcus aureus

“…Staphylococcus aureus ( S. aureus ) , known as one of the most frequent strain usually causes food poisoning and widespread infection, and is a risk factor for exacerbating HAPUs. It comes from superficial skin and other soft tissue infections to life threatening toxic shock, skeletal system, circulatory system, respiratory system, implantable medical devices, and the blood stream 4-6. At present, S. aureus -associated HAPUs have been increasing year by year.…”