Changes in Vancomycin Pharmacokinetics in Critically Ill Infants

Abstract

We aimed to assess the pharmacokinetics of vancomycin in critically ill infants, and to evaluate the standard recommended dose oJ 10 mglkg 6 hourly. All infanfs admitted to the Baragwanath Hospital fCU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescrib"ed for an infectiVe insult and who had parental consent, were included in the study. Vancomycin was infused over 60 minutes. Serum samples were taken immediately before the dose and at 30, 60, 120 and 300 minutes after the end of the vancomycin infusion, on days 2 and 8 of therapy. Extrapolated peak concentration (Cmax), trough concentration (Cm in), apparent volume of distribution (Vd), elimination half-life (tOe!) and clearance (CL) were determined for each patient. Day 2 values were compared with those of day 8. Day 2 serum concentrations were assayed on 20 patients and day 8 concentrations in 15. The mean vancomycin Vd on day 2 (0.81I1kg) was significantly (P=0.007) larger than that on day 8 (0.44 IIkg). The change in Vd resulted in a significant change in mean Cmax (29.1 vs 35.5 p.g/ml) (P=0.02) and mean tOe! (5.3 vs 3.4h) (P=O.OI) over the treatment period. Critically ill infants displayed a large initial volume of distribution which probably resulted from aggressive fluid resuscitation. This also results in a large variation in other pharmacokinetic parameters, namely Cmax and tOe!' Although the routine monitoring of vancomycin serum concentrations remain controversial, we feel that in view of these large pharmacokinetic variations, the critically ill infant is a specific group where monitoring of vancomycin serum levels is indicated.

Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis

“…intravascular volume, composition of plasma proteins, and renal and hepatic function [13]. As a consequence of these variables, variations in PK characteristics have been demonstrated for antibiotics such as ciprofloxacin [14], vancomycin [15] and imipenem [16]. The current study shows lower C max and AUC 0-∞ and higher V ss , CL T and CL R for total ertapenem compared with those observed in young healthy volunteers [9,17].…”

Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing

“…Critically ill patients have many characteristics that differ from those of healthy volunteers and general ward patients, notably abnormal fluid balances, different volumes of distribution, altered protein metabolism and low albumin levels [10,11,12,13,14,15,16,17]. Hence maximisation of b-lactam therapy may require dosing regimens specific to the critically ill.…”

Fluid shifts have no influence on ciprofloxacin pharmacokinetics in intensive care patients with intra-abdominal sepsis

“…1. This is contrary to what has been described with drugs such as aminoglycosides and vancomycin [4,[9][10][11][12]. Aminoglycosides and vancomycin distribute into extracellular fluids [13,14].…”

“…The volume of distribution of ciprofloxacin remained relatively unchanged despite fluid shifts affecting the extravascular and extracellular space, and did not differ in infants less than 12 months compared with older infants where body water content differs significantly from the former group [15]. The clinical implication of this means that a dose of ciprofloxacin will produce similar C max over the septic insult [15], in contrast to, for example, vancomycin [9].…”

“…Aminoglycosides and vancomycin distribute into extracellular fluids [13,14]. The volume of distribution for these drugs may increase in the critically ill patient as a result of fluid shifts and, as a consequence, higher doses than those conventionally recommended may be needed to optimise plasma concentrations and to ensure clinical efficacy [4][5][6][9][10][11][12]. The volume of distribution of aminoglycosides and vancomycin therefore changes over the time-course of a severe infection [9,11].…”