title: Vancomycin pharmacokinetics in patients with severe burn injuries.
abstract: Vancomycin is used in patients with severe burns and methicillin-resistant Staphylococcus aureus (MRSA) infection. This study investigated vancomycin pharmacokinetics in people with burns in comparison to people without burns and examined the factors contributing to pharmacokinetic variability. This was a retrospective, case-control study of hospitalised burns patients compared with a control patient cohort administered vancomycin without burn injury. Vancomycin pharmacokinetic parameters were determined using therapeutic drug monitoring data and a population pharmacokinetic modelling approach employing a two-compartment pharmacokinetic model. The impact of patient characteristics on vancomycin clearance was explored. Vancomycin clearance was significantly higher (p<0.001) in burns patients (5.9+/-3.1L/h, n=37) when compared to control patients (3.4+/-1.8 L/h, n=33), as was estimated creatinine clearance, which was correlated to drug clearance in burns patients (r(2)=0.64). There was no significant change in volume of distribution between patient groups. The majority of patients received a dosing regimen of 1g twice daily, resulting in significantly (p=0.004) lower serum trough concentrations in patients with burns (median, 6.4 mg/L; range, 0.2-22.3mg/L) than control (median, 9.2mg/L; range, 4.0-29.8 mg/L). Higher clearance and lower serum vancomycin concentrations in people with severe burn may increase the risk of suboptimal bactericidal action and the development of resistance highlighting the need for dosage individualization.
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Dolton
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xu
authors.forename: Elaine
authors.initials: E
authors.lastname: Cheong
authors.forename: Peter
authors.initials: P
authors.lastname: Maitz
authors.forename: Peter
authors.initials: P
authors.lastname: Kennedy
authors.forename: Thomas
authors.initials: T
authors.lastname: Gottlieb
authors.forename: Evette
authors.initials: E
authors.lastname: Buono
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McLachlan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002056:Burns / Q000188:drug therapy / Q000378:metabolism*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012189:Retrospective Studies; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin