title: Vancomycin pharmacokinetic models: informing the clinical management of drug-resistant bacterial infections.
abstract: This review aims to critically evaluate the pharmacokinetic literature describing the use of vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Guidelines recommend that trough concentrations be used to guide vancomycin dosing for the treatment of MRSA infections; however, numerous in vitro, animal model and clinical studies have demonstrated that the therapeutic effectiveness of vancomycin is best described by the area under the concentration versus time curve (AUC) divided by the minimum inhibitory concentration (MIC) of the infecting organism (AUC/MIC). Among patients with lower respiratory tract infections, an AUC/MIC ≥400 was associated with a superior clinical and bacteriological response. Similarly, patients with MRSA bacteremia who achieved an Etest AUC/MIC ≥320 within 48 h were 50% less likely to experience treatment failure. For other patient populations and different clinical syndromes (e.g., children, the elderly, patients with osteomyelitis, etc.), pharmacokinetic/pharmacodynamic studies and prospective clinical trials are needed to establish appropriate therapeutic targets.
authors.affiliation: Department of Pediatrics, Division of Clinical Pharmacology, University of Utah School of Medicine, 295 Chipeta Way, Salt Lake City, Utah 84108, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Roberts
authors.forename: Tian
authors.initials: T
authors.lastname: Yu
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Constance
authors.forename: Catherijne A J
authors.initials: CA
authors.lastname: Knibbe
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D006801:Humans; D014640:Vancomycin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: MRSA; Staphylococcus aureus; aminoglycoside; antibiotic; critical care; glycopeptide; infectious disease; pharmacodynamic; pharmacometrics