title: Impact of area under the concentration-time curve to minimum inhibitory concentration ratio on vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus bacteraemia.
abstract: There have been few clinical studies on the association between the vancomycin 24-h area under the concentration-time curve (AUC24) to minimum inhibitory concentration (MIC) ratio and vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infections. To examine this association and to establish a suitable cut-off value for AUC24/MIC, a multicentre prospective observational study was conducted in patients with MRSA bacteraemia. Data were collected on all patients aged ≥18 years with MRSA bacteraemia treated with vancomycin for ≥72 h without dialysis. The MIC was determined by broth microdilution (BMD) and Etest. Treatment failure was defined as (i) 30-day mortality, (ii) persistent bacteraemia (≥7 days) and (iii) recurrence (≤30 days after completion of therapy). AUC24 was estimated by a Bayesian approach based on individual vancomycin concentrations. The AUC24/MIC cut-off value for differentiating treatment success and failure was calculated by Classification and Regression Tree (CART) analysis. In total, 117 patients were enrolled, among which vancomycin treatment failure occurred in 38 (32.5%). In univariate analysis, high vancomycin MIC and low trough levels were unrelated to treatment outcomes. In the CART analysis, low vancomycin AUC24/MIC [<392.7 (BMD) and <397.2 (Etest)] was associated with treatment failure. In multivariate analysis, low AUC24/MIC was a risk factor for treatment failure [adjusted odds ratio (aOR)=3.50, 95% confidence interval (CI) 1.39-8.82 by BMD; aOR=5.61, 95% CI 2.07-15.24 by Etest]. AUC24/MIC is associated with vancomycin treatment outcomes in MRSA bacteraemia, and seeking individualised AUC24/MIC ratios above target (>400) may improve treatment outcomes.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Kyoung-Ho
authors.initials: KH
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. Electronic address: hbkimmd@snu.ac.kr.
authors.forename: Hong Bin
authors.initials: HB
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Hyung-sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Myung Jin
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Internal Medicine, Konyang University Hospital, Daejeon, South Korea.
authors.forename: Younghee
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Gayeon
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Nak-Hyun
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Moonsuk
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Chung-Jong
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Pyoeng Gyun
authors.initials: PG
authors.lastname: Choe
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Wan Beom
authors.initials: WB
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Eu Suk
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Kyoung Un
authors.initials: KU
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Nam Joong
authors.initials: NJ
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Eui-Chong
authors.initials: EC
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Myoung-don
authors.initials: MD
authors.lastname: Oh
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D016470:Bacteremia / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D017211:Treatment Failure; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Area under the concentration–time curve; Methicillin-resistant; Minimum inhibitory concentration; Pharmacokinetics; Staphylococcus aureus; Vancomycin